BlOLOGy ^ 19th Annual Meeting · 2008. 7. 17. · Influence of plutonium 238 on the sensitive endosteal layer in mice L. Navrátil, J. Pospíšil (Praha, ČSSR) Changes of levels

PROGRAMME

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BlOLOGy^ 19th

Annual Meeting

PRAGUE

EUROPEAN SOCIETYFOR RADIATION BIOLOGY

19th Annual Meeting

Prague, August 26-30, 1985

PROGRAMME

Organizer: Czechoslovak Medical Society J. E. Purkyne

Czechoslovak Society of Nuclear Medicine

and Radiation Hygiene

PATRONAGE

JAROSLAV PROKOPEC

Minister of Health of the Czech Socialist Republic

EMIL MATEJICEK

Minister of Health of the Slovak Socialist Republic

BOHUMIL KVASIL

President of the Czechoslovak Academy of Sciences

RUDOLF T. NIEDERLAND

President of the Czechoslovak Medical Society

ZDENEK CESKA

Rector of Charles University, Prague

FRANTISEK STAFA

Mayor of Prague

E U R O P E A N S O C I E T Y F O R R A D I A T I O N

B I O L O G Y

CouncilPresident

Honorary President

Secretary-Treasurer

Members

P

E.

R.

GT.J.HJ.O

. METALLI (Rome/I)

H. BETZ (Lieqe/B)

. GOUTIER(Liege/B)

. BOOZ(Angleur/B)BRUSTAD (Oslo/N)E. HIDVEGI(Budapest/H). JUNG (Hamburg/FRG)MAISIN (Mol/B). VOS(Rotterdam/N)

Mrs. 1. SZUMIEL(Warsaw/P)Mrs. M. BIANCHI (Geneve/CH)WJ.A.L.A.

.A. CRAMP (London/UK)F. DUPLAN(Bordeaux/F)LEONARD (Mo!/B)REVESZ(Stockho!m/S)SMiD(Pribram/CS)

O 8 G A N ( 7 F R O F T H E A N N U A L M E E T I N G

ZDENEK DIENSTBIER

Chair of Biophysics and Nuclear MedicineMedical Faculty of the Charles UniversityPrague

S C I E N T I F I C C O M M I T T E E

ZDENEK DIENSTBIERMrs. EVAAHLFRSPAVEL KUNAJAN POSPISILMILAN POSPISILZDENEK PROUZAMILOSLAVSKALKAVLADIMIR SVOBODAANTON(N SMiDP. METALLIL. SZTANYIK

PrahaKosiceHradec Kra'ovePrahaBrnoPrahaBrnoPrahaPribramRomaBudapest

O R G A N I Z I N G C O M M I T T E E

ANTONI'N SMID Secretary GeneralMrs. VALERIE FOLTYNOVAALOIS GARBAMrs. ZDENAJIZBOVAVLADIMIR KOFRANEKMIROSLAV KUBiCEKJAN POSPISILMrs. JAROSLAVA SMUTNAJIRI SONKA

SOCIAL PROGRAMME

MONDAY, AUGUST 26, 19858 p.m. WELCOME RECEPTION

at the Palace of CulturePanorama Restaurant

TUESDAY, AUGUST 27,19858 p.m. ORGAN CONCERT

ST. NICOLAS'CHURCHPraha 1-Mala Strana

WEDNESDAY, AUGUST 28, 19858 p.m. BEER PARTY ,,U FLEKO"

Kremencova 9, Praha 1

on invitation

on invitation

on invitation

PROGRAMME ORGANIZED BY CEDOK

TUESDAYAugust 279a.m.

WEDNESDAYAugust 289a.m.2.30 p.m.

THURSDAYAugust 299 a.m.

FRIDAYAugust 309 a.m.8 p.m.

SATURDAYAugust 319 a.m.

Visit to the NATIONAL GALLERY IN THE ST.GEORGE MONASTERY housing Gothic,Price: Sfrs 17,-/Kcs 80

Visit to the STRAHOV MONASTERY andETHNOGRAPHIC MUSEUMPrice: Sfrs 16,-/Kcs 75SIGHTSEEING TOUR OF PRAGUEPrice: Sfrs 17,- /Kcs 80

Half-day tour to KONOPlSTE CASTLE.Price: Sfrs 37,-/Kcs 176

Visit to the FORMER JEWISH GHETTOOF PRAGUEPrice: Sfrs 17,-/Kcs 80Performance in the theatre ,,NA ZABRADLf"Price: Sfrs 12,-/Kcs 55

Postcongress tour to Southern Bohemia.Visit to the town of TABOR and to HLUBOKA,a romantic chateau built in Tudor style(one-day trip).Price: Sfrs 77,- /Kcs 370

G E N E R A L I N F O R M A T I O N

Place of the Meeting:

The Meeting will take place in the Palace of Culture fromAugust 27 to 30, 1985.

Secretariat:before and after the Congress:Czechoslovak Medical Society J. E. PurkyneVitezneho unora 31, P. O. Box 88CS- 120 26Praha2phone: 294141, 297271telex: 121 293during the Congress:Palac kultury5. kvetna 65CS- 140 09Praha4phone:4171111

R E G I S T R A T I O N O F F I C E

The registration of the participants will start on Monday,August 26 at 12 p.m. at the Palace of Culture

O f i c e H o u r s

August 26, 1985-12 a.m. to 8 p.m.August 27, 1985- 8 a.m. to 4 p.m.August 28, 1985- 8 a.m. to 4 p.m.August 29, 1985 - 8 a.m. to 4 p.m.August 30, 1985- 8 a.m. to 12 p.m.

O R I E N T A T I O N P L A N O F T H E P A L A C EO F C U L T U R E

FORTH

FLOOR

THIRD FLOOR HALL B

CAFE

SECONDFLOOR

FIRST FLOOR HALL C

GROUNDFLOOR

HALL A

FOYERHALLCPOSTERS

REGISTRA-

TION

WELCOMERECEPTIONPANORAMARESTAURANT

EXHIBITIONCEDOKEXCHANGEOFFICE

POST OFFICECLOAKROOMSNACKBAR

T I M E T A B L E

DAY

MONDAY

TUESDAY

WEDNESDAY

THURSDAY

FRIDAY

SATURDAY

DATE

26.8. 1985

27. 8. 1985

MORNING

Sessions

28. 8. 1985 ' Sessions

29. 8. 1985

30.8. 1985

31.8. 1985

Sessions

Sessions

C e d o k ' s P

AFTERNOON

Registration

Sessions

SessionsSightseeing tourof Prague

| Sessions

Sessions

r o g r a m m e

EVENING

Welcome Reception

Organ

Concert

Beer Party

Free

Free

S C I E N T I F I C PROGRAMME

LIST OF S E C T I O N S

1 DNA Damage and Repair I - III

2 Pathophysiology of radiation damage I - III

3 Radiation Hematology

4 Modification of Radiation Effects I — II

5 Dosimetry, LET. RBEI - II

6 Tumour Irradiation I — ill

7 Chemical Radioprotection

8 Effects of Low Doses

9 ELEG/EULEP Symposium: Late Effects of Irradiation

T I M E S C H E D U L E

Tuesday Morning - August 27,1985

9 - 1 0 a.m. Opening Ceremony - Hall A

10 - 12.30 Hall A: DNA damage and repair I

Hall B: Modification of radiation effects I

Hall C: Tumour irradiation I

Poster sessions - Foyer of the hall C11 — 12.30 — Pathophysiology of radiation damage

Tuesday Afternoon — August 27,1985

2 — 5 p.m. Hall A: DNA damage and repcir II

Hall B: Dosimetry, LET, RBE I

Hall C: Tumour irradiation II

Poster sessions3 — 5 p.m. — Modification of radiation effects,

chemical radioprotection

Wednesday Morning — August 28,1985

9 a.m. — 1 p.m. Hall A: Pathophysiology of radiation damage

Hall B: Radiation hematology

Hall C: Chemical radioprotection

Poster sessions

11 i.m. - 1 p.m. - DNA damage and repair- Varia

Thursday Morning — August 29

9 - 12.30 Hall A: DNA damage and repair III

Hal! B: Modification of radiation effects II

Hall C: Pathophysiology of radiation damage II

Poster sessions

11 - 12.30 - Dosimetry. LET, RBE- Effects of low doses,

late effects of irradiation

Thursday Afternoon — August 29

2 — 4 p.m.

2 — 3 p.m. Hall A: Tumour irradiation 111

3 - 4 p.m. Hall A: Dosimetry, LET, RBfc II

2 - 4 p.m. Hall B: Effects of low doses

2 - 4 p.m. Hall C: Pathophysiology of radiation damage III

Poster sessions2 — 4 p.m. — Tumour irradiation

- Radiation Hematology

Friday — August 30

9 a.m. - 3 p.m.

ELEG/EULEP Symposium: Late effects of irradiation

Morning session

Afternoon session

TUESDAY MORNING - AUGUST 27,1985

9 - 1 0 Opening Ceremony - Hall A10 - 12.30

Hall A: DNA damage and repair IChairman: E. J. HidvegiVice-Chairman: V. Brabec

E. Aufderheide, H. Rink, L. Hieber, G. Kraft(Bonn, FRG; Darmstadt, FRG)Heavy ion induced DNA strand breaks and their repair: Dependen-ce on LET, particle energy and dose

G. Kraft, R. Roots(Darmstadt, FRG; Berkeley, UK)Heavy ion induced double and single strand breaks in SV40 DNA

S. A. Sabovljev, A. M. George, W. A. Cramp, G. Harris, M. Hedges,S. Hornsey(Hammersmith, UK)Radiobiological properties of the quaternary structure of cellularDNAA. M. Duplaa, G. V. Fazakerley, A. Guy, W. Guschlbauer, R. Teoule(GIF-S/Yvette Cedex, F; Grenoble Cedex, F)Synthetic oligonucleotides: A new tool for the analysis of DNAchain breakage and DNA structure modifications

COFFEE BREAK

W. Pohlit and M.Kramer(Frankfurt/Main, FRG)Kinetics of repair and misrepair in mammalian tumour cellsE. Dikomey and J. Franzke(Hamburg, FRG)Three classes of DNA strand breaks after X-irradiation

M. Skalka, M. Cejkova(Brno, CSSR)Potentiation of radiation damage to DNA and chromatin in thepresence of 1,10-phenanthroline - copper complexV. Brabec, O. Vrana(Brno, CSSR)The effect of combined treatment with platinum complexes andradiation on DNA in vitro


9—10 Opening Ceremony — Hall A

10 - 12.30

Hall B: Modification of radiation effects I

Chairman: L. ReveszVice-Chairman: J. Sonka

K. S. Chertkov(Moscow, USSR)Modification of radiation effect by adeninnudeotides

O. Vos, W. S. D. Roos-Verhey(Rotterdam, NL)The effect of changes in intracellular gluthathione level on radio-sensitivity

O. Sapora, J. C. M. Bremner, V. Capuano, B. R. Guerra, A. Maggiand G. Simone(Roma and Bologna, I)Does BSO affect cell radiosensitivity only by reducing GSH content?

G. Simone, J. C. M. Bremner, M. Tamba(Bologna, I)B. R. Guerra and M. Quintiliani(Roma, I)Thiol peroxyl radicals and radiation induced enzyme inactivation

A. W. T. Konings(Groningen, NL)Differential modification of subcellular radiosensitivity

COFFEE BREAKH. Durchschlag, P. Zipper(Regensburg. FRG; Graz, A)Post-irradiation inactivation, protection, and repair of the sulf-hydryl enzyme malate synthase

E. Magdon, E. Schroder(Berlin, GDR)Modification of radiation effects, pharmacokinetics, and neuroto-xicity of ISO-metronidazole

Z. V. Kuropteva, M. K. Pulatova(Moscow, USSR)New aspects of molecular mechanisms of action of nitrocompoundradiosensitizers

A. G. Konoplyannikov(Obninsk, USSR)Hyperthermic radiosensitization and hyperthermic kiiiing in mam-malian cells

L. Kh. Eidus, L N. Kublik, Yu. N. Korystov, A. M. Vexler(Pushchino, USSR)The enhancement of reproductive cell death by postirradiationhypoxia and low intracellular pH

G. Seibold, E. Budzicka(Giessen, BRD; Warsawa, P)Chromatin features as a factor of radiosensitivity

TUESDAY MORNING - August 27, 1985

9 - 1 0 Opening Ceremony - Hall A1 0 - 12.30Hall C: Tumour irradiation IChairman: F. H. GlaserVice-Chairman: J. Zamecnfk

J. Zamecnfk, V. Mlejnska(Praha, CSSR)Philosophy of dose-fractionation in radiotherapy

K. Prokes, M. Lokajfcek(Praha, CSSR)Radiomodifiers and optical choice of fractionation regimes

K. H. Merkle(Berlin, GDR)Radiobiology and the concept of individualized cancer therapy

L. Juling-Pohlit(Frankfurt, FRG)In vivo repair of potentially lethal damage

COFFEE BREAK

I. Szumiel, D. Wlodek, K. J. Johanson, E. Budzicka, E. Niepokoj-czycka(Warsaw, Poland; Uppsala, Sweden)Inverse cross-sensitivity to UV-C and X or gamma radiations oftwo strains of L5178Y mouseD. Van Beuningen, C. Streffer(Essen, FRG)Survival of human melanoma cells after X-rays, hyperthermia andneutron therapyK. Cieszka, R. Gurbiel, M. Kapiszewska, K. Hyrc(Cracow, P)Effect of in vitro exposure to X rays and hypothermia on of hamstermelanoma cellsL. Perloky, A. Fonagy, E. J. Hidvegi(Budapest, H)Combined effect of X-irradiation and dibromodulcitol on hyper-thermic treated P388 Tumor


9 - 1 0 Opening Ceremony - Hall A

Poster sessions: 11 - 12.30

Pathophysiofogy of radiation damage I

Chairman: Mrs. E. AhlersVice-Chairman: I. Datelinka

B. Todorov(Stara Zagora, BG)Enzyme test for early prognostication heaviness of radiation diseaseat lambs

M. Rejholcovd, J. Wilhelm(Praha. CSSR)Relationship between lipolysis and lipofuscinlike pigments forma-tion in adipose tissue after whole-body gamma irradiation of rats

J. Wilhelm(Praha, CSSR)Lipofuscin-like pigments time courses in erythrocytes and spleenof whole-body gamma irradiated rats

M. Kowalska(Warsaw, P)Organically bound tritium in the major brain phospholipids of ratslifetime exposed to tritiated water and tritiated food

J. Bohacek, B. Hosek, J. Kautska, J. Sikulova(Brno. CSSR)Activity of purine nucleoside phosphorylase in fractionated erythro-cytes of rats after gamma irradiation

G. Khogiakhmedov, K. N. Nishanbaev, D. Kh. Khamidov(Tashkent, USSR)Effect of preincubative irradiation on cAMP of chicken thyroidgland in ontogenesis

E. Ahlersova, I. Ahlers, M. Toropila, I. Datelinka(Kosice. CSSR)Thyroid hormones in irradiated rats

P. Rozsíval, í. Obenberger, J. Sládková(Hradec Králové, ČSSR)Lens changes after 60Co irradiation

O. Parízek, H. Mohelská, V. Hynčica and E. Hartlová(Praha, ČSSR)Influence of plutonium 238 on the sensitive endosteal layer in mice

L. Navrátil, J. Pospíšil(Praha, ČSSR)Changes of levels of certain prostanoids in the blood plasma ofwhole-body irradiated rats

B. Šmajda, I. Ďatelinka, I. Ahlers(Košice, ČSSR)Feeding behaviour in X-irradiated rats

TUESDAY AFTERNOON - AUGUST 27,1985

2 - 5 p.m.

Hall A: DNA damage and repair II

Chairman: I. SzumielVice-Chairman: L. Benes

V. Drasil(Brno, CSSR)Repair and misrepair following irradiation

M. Belli, S. Mazzucato, M. Morando, G. Moschini, O. Sapora,M. A. Tabocchini(Roma, Padova, I)A new facility for radiobiological studies with proton beams: Sur-vival and DNA damage in V-79 cells

L. HieberandG. Kraft(Wiirzburg, Darmstadt, FRG)G2 Delay of V79 cells exposed to heavy ions from neon to uranium

L. Benes, E. Rotreklova(Brno, CSSR)Distribution of radiation damage of DNA in cell population andin single cells after homogeneous irradiation with fast neutrons

J. Franzke, E. Dikomey(Hamburg, FRG)Influence of hyperthermic treatments on the repair of X-ray inducedDNA strand breaks

COFFEE BREAK

O. Ostling and K. J. Johanson(Uppsala, S)Pronounced DNA fragmentation following treatment with bleomy-cin and with high doses of gamma irradiation. A microelectropho-retic study of single mammalian cells

K. Langrock, E. - J. Langrock(Leipzig, GDR)About use of bromine-82 labelled ethidiumbromide in DNA inves-tigations

G. P. van der Schans, O. Vos1), W. S. D. Roos-Verheij and P. H, M.Lohman(Rijswijk, NL; 1. Rotterdam, NL)The influence of oxygen on the induction of radiation damage inDNA in mammalian cells after sensitization with DEM and BSO

S. Gundy, L. P. Varga and M. A. Bender1)(Budapest, H; 1. Upton NY, USA)X-ray and cytosine-arabinoside (ARA-C) induced chromosomeaberrations and unscheduled DNA synthesis in the Gi-phase ofthe cell cycle

TUESDAY AFTERNOON - AUGUST 27, 1985

2 - 5 p.m.Hall B: Dosimetry, LET, RBE IChairman: J. KieferVice-Chairmon: J. Novotný

J. J. Broerse and J. Zoetelief(Rijswijk, NL)Practical aspects of dosimetry for radiobiologyJ. W. Hansen, K. J.OIsen(Roskilde, DK; Herlev, DK)High-LET radiation and high-level dosimetry

A. Sedlák(Praha, ČSSR)Interpretation of cell survival curves with microdosimetryE. A. Krasavin, S. Kozubek(Dubna, USSR)Mechanisms of the biological effect of different ionizing radiationCOFFEE BREAKJ. Kiefer(Giessen, FRG)LET and RBE - lesions from yeast and mammalian cellsE. Schneider, J. Kiefer, K. J. Weber(Giessen, FRG)Radiochromic detectors as dosimeter and model system for biolo-gical high LET radiation experiments

E. Magdon(Berlin, GDR)RBE of fast neutrons (6.2 MeV), acute and late effectsJ. Novotný(Praha, ČSSR)Accuracy required in clinical dosimetryL. A. Buldakov, E. Lyubchcmskiy, Z. Bukhtoyarova, R. Erokhin et al.(Moscow, USSR)Influence on carcinogenesis of radionuclides emmiting high LETradiation

TUESDAY AFTERNOON - AUGUST 27, 1985

2 - 5 p.m.

Hall C: Tumour irradiation II

Chairman: W. A, Cramp

Vice-Chairman: M. Lokaji'cek

F. Zywietz and H. Jung(Hamburg, FRG)Decay of thermoradiosensitization in the R1H tumour after com-bined treatments with X-rays and hyperthermia

A. Vacek, D. Rotkovska, A. Bertom'ckova, T. Tacev(Brno, CSSR)Differences in radioprotective effects of hypoxic hypoxia in normaltissues and in experimental tumours

David J. Chaplin(Vancouver, BC, CND)The effect of artificially induced hyperglycaemia on the radiationresponse of the Lewis lung carcinoma

Siracka, E., Revesz, L.(Bratislava, CSSR; Stockholm, S)A consideration of the role of vascularity in response of tumors toradiosensitizers

COFFEE BREAK

E. Unger(Budapest, H)Histological examination of combined effects of dibromdullcitetreatment and differently fractionated X-irradiations in transplan-ted solid Ehrlich carcinoma of mice

F. H. Glaser, D. Grimm, K.-H. Heider(Erfurt, Halle, GDR)Time-dose-relationships at high-dose-rate afterloading in gyneco-logical tumortherapy

D. Grimm, I. Grimm, F. H. Glaser, R. A. Weidhase, J. Schindler(Halle, Erfurt, GDR)DNA-distribution of carcinoma of the endometrium before, duringand after high-dose-rate afterloading irradiation

R. R. Wick, H. Spiess*, W. Gossner(Neuherberg, Munchen*, FRG)Long term effects after therapeutic administration of different dosesof 224Ra (thorium X)+

D. Kob, A. Kriester(Jena, GDR)About dose-time behaviour at brachy therapy

TUESDAY AFTERNOON - AUGUST 27,1985

Poster sessions3 — 5 p.m.

Modification of radiation effects,Chemical radioprotection

Chairman: T. Pantev :

Vice-Chairman: I. Vodicka

S. Cabadaj, J. Filova, M. Praslicka(Kosice, CSSR)Offspring's radioresistance increased by maternal stimulation

G. L. Gazso, A. Dam(Budapest, H)The radiosensitizing effect of acetone at various oxygen concen-trations

S. K. Khalikov, L. SH. Rabinovich. P. Mirkhamidova P.(Tashkent, USSR)Effect of radiation and modificators of radiation casualties on ani-mals cyclase system

Ju. N. Korystov, F. B. Vexler(Pushchino, USSR)The oxygen effect in bacteriophage irradiated in different media

H. Nechev, P. Salovski, V. Shopova(Pleven. BG)Metabolism and biological activity in the combined applicationof americium-241 and external ionizing radiation

Z. Paskalev, I. Pejankov, E. Hadjidekova(Sofia, BG)Conformation changes of blood plasma protein macromoleculesof rats after the combined action of 89Sr or iUCe and the phosp-hororganic pesticide phosalon

I. Skardova, K. Fried, R. Skarda(Kosice, CSSR)Comparison of radioprotectivity of some substances in chickens

I

J, Vávrová, P. Petýreic(Hradec Králové, ČSSR)Changes induced in the hematopoietic and lymphoid system ofirradiated mice by the double-stranded RNA

A. M. Vexler, L. L. Litinskaya(Pushchino, Moscow, USSR)The effect of hyperthermia and hypoxia on intracellular pH

S. Voronina(Moscow, USSR)Radiosensitization of ascite tumour cells by metronidazole in dif-ferent phases of tumours development

G. Zasukhina, W. Chekova, N. Alekhina(Moscow, USSR)Modification of radiation and radiomimetic effects by interferonsin human cells

M. Zima, I. Vodička(Hradec Králové, CSSR)The O2 effect on reparation processes in rat bone marrow afterwhole-body irradiation

P. Zipper, M. Kriechbaum, R. Wilfing, H. Durchschlag(Graz, A; Regensburg, FRG)Small-angle X-ray scattering study on the influence of additiveson the X-ray induced aggregation of the sulfhydryl enzyme malatesynthase

A. Bajrakova, V. Manchev(Sofia, BG)MEA and AET studied for antimutagenic effects by the test of mor-phologic sperm-head anomalies (MSHA) in the mouse

D. Benova, I. Rupova(Sofia, BG)Testing WR 2721 and ATP for antimutagenic potency against ra-diation-induced somatic-cell chromosome aberrations in the mou-se

K. Kropacova, E, Misurova(Kosice, CSSR)Possibilities of modification of latent radiation injury in radiationinjury in rat liver by radioprotective agents

T. Pantev, M. Khristova(Sofia, BG)Effects of adeturone on mineral and protein metabolism in themaxillodental system of irradiated rats

E. Ronai, L. Tretter, L. Meszaros, Gy. Benko, I. Horvath(Budapest, H)Na-succinate, as a protective compound against lipid peroxida-tion and acute 60-Co-gamrna irradiation

Ts. Vranska, T. Pantev, K. Kusova, N. i. Ryzhov, B. S. Phedorenko(Sofia. BG; Moscow, USSR)Electrophoretic mobility of erythrocytes from gamma- or alpha-irradiated rats protected by adeturone

I. Vodicka, V. Chmelar, M. Zima, K. Volenec(Hradec Kralove, CSSR)PO2 — tissue distribution and its relation to the action of the hy-poxic cell radiosensitizer (metronidazole)

M. Dostal, P. Kuna, P. Petyrek(Hradec Kralove. CSSR)An interspecies comparison of radioprotective efficacy of 3:1 com-bination (CM) of cystamine (C) and 5- methoxytryptamine (M)

WEDNESDAY MORNING - AUGUST 28,1985

9 a.m. - 1 p.m.

Hall A: Fathophysiology of radiation damage I

Chairman: J. MaisinVice-Chairman: M. Pospi'sil

G. J. Koteles(Budapest, H)Recent aspects in the pathophysiology of radiation injury

Z. Somosy, T. Kubasova, G. J. Koteles(Budapest, H)Morphological detection of surface charges of X-irradiated fibro-blasts

M. Koter, M. Bryszewska(Lodz, P)The effect of gamma irradiation on the phosphatidylcholine mem-branes

V. G. Kondratenko, L. F. Ganzenko(Moscow, USSR)Effect of testosterone on synthesis of nucleic acids in germ cellsof irradiated animals

C. B. Seymour and C. Mothersill(Dublin, Ireland)Longterm survival of clonogenic survivors from radiation experi-ments

W. Miiller, H. G. Miltenburger, G. Kraft(Darmstadt, FRG)Chromosomal damage after heavy ion exposure

S. Pampfer, C. Streffer(Essen, FRG)Prenatal death, congenital malformations and chromosomal aber-rations after neutron- and X-irradiation of mouse embryos 1 hourafter conception

M. Hauer-Jensen, T. Sauer, T. Berstad, K. Nygaard(Oslo, N)Amelioration of late radiation enteropathy by pancreatic duct oc-clusion

COFFEE BREAK

W.-U. Miiller, C. Streffer(Essen, FRG)Kinetics of micronucleus formation in preimplantation mouse em-bryos

J. Holland, L. Korosi, Gyongyi Mangel, Gy. Katona and L. D. Szabo(Budapest, H)Effect of whole-body gamma irradiation on liver microsomal pro-tein synthesis of vitamin-E deficient rabbits

K. J. Johanson, S. Sundell-Bergman and H. Cerda(Uppsala, S)Doses and effects from 125l-triiodothyronine in cells and organisms

A. Vaglenov, A. Karadzhov(Sofia, BG)Gamma dose rate effect on genetic damage in mammals. Estima-tion of human risk

I. M. Parkhomenko, Yu. B. Kudrjashov, Yu. Yu. Chirkov, B. A. Raev(Moscow, USSR)Molecular mechanisms of stimulating effect of X-rays low doseson isolated mammalian ceils

P. A. Khakimov, N. KH. Shadieva, A. B. Akbarov, JU. N. Islamovm,M. K. Parmanov, R. K. Siddikov(Tashkent, USSR)Effect of gamma irradiation and complexes of some 3D-ions withbioactive ligands on biophysical characteristics of cells and cellstructures of mammalian blood

W. Schmidt, K. Wulff, V. Grimm, A. Reinke(Greifswald, GDR)Metabolism of vitamin B and radiation effect.


9 a.m. — 1 p.m.

Hall B: Radiation Hematology

Chairman: P. MetalliVice-Chairman: V. Svoboda

T. M. Fliedner(Ulm.FRG)Pathophysiologicai mechanisms of tolerance of hemopoietic sys-tems to chronic low level radiation exposure

L. Fabry(Mol, B)Chromosome aberrations induced in human lymphocytes by lowdoses of Co-60 gamma-rays delivered at high and low dose-rate

W. Calvo, O. Prummer, F. Carbonell and T. M. Fliedner(Ulm.FRG)Reconstitution of the lymph nodes of dogs after fractionated totalbody irradiation and transfusion of fetal liver cells

W. Porschen, H. Muhlensiepen, J. Marx, C. Lindberg, J. Booz, L. E.Feinendegen(Julich, FRG)RBE-determination of acute in vivo-effects from very low dose who-le-body exposure with different radiation qualities by three in vitroassays

Z. Pojda(Warsaw, P)In vitro radiosensitivity of murine and human progenitors of he-mopoietic colonies in plasma clot diffusion chambers (PCDC)

W. W. Jedrzejczak, E. Urbanowslca(Warsaw, P)A search for genetic regulation of postirradiation recovery of ery-thropoiesis in mice

E. Necas, V. Znojil(Praha. tSSR)Oscillation in stem cell proliferation after 1.5 and 2.6 Gy total bodyirradiation

COFFEE BREAK

J.Vacha.V.Znojil.J.Hola(Brno, CSSR)Use of labelled iron for determination of postirradiational intensityof erythropoiesis in the base of ferrokinetic measurements

V. Svoboda(Hradec Kralove, CSSR)Early reparation of hemopoiesis after local 20 Gy gamma irradia-tion in rats

Zs. Almassy, B. Kanyar, G. J. Koteles(Budapest, H)Frequency of micronuclei in X-irradiated human lymphocytes

D. Jaskulski, C. Szczylik, W. W. Jedrzejczak(Warsaw, P)Lack of correlation between formation of spleen colonies in vivoand formation of granulocyte-macrophage colonies in vitro duringpostirradiation recovery of hemopoiesis in mice heterozygous atsteel locus

M. Z. Ratajczak, W. W. Jedrzejczak(Warsaw, P)Postirradiation recovery of eosinophilic granulocyte system in micemutant at steel locus

M. Minkova, T. Pantev, V. Tenchova(Sofia. BG)Attempt to assess extent and outcome of radiation damage to ratsusing leukocyte nuclein acid levels


9 a.m. - 1 p.m.

Hall C: Chemical radioprotection

Chairman: R. GoutierVice-Chairman: P. Kuna

P. G. Zherebshenko(Moscow, USSR)Modification of radiation effects

K. Bodo, Gy. Benko(Budapest, H)The effect of radioprotectors and irradiation on the platelet mono-arnine oxidase activity

Gy. Horvath and Gy. Benko(Budapest, H)Effect of AET, cysteamine and WR-2721 on the prostacyclin for-mation of rat aorta, arachidonic acid and ADP induced plateletaggregation

J. W. Hiilsewede, D. Schulte-Frohlinde(MiJlheim/Ruhr, FRG)Formation of double-strand breaks in E. coli by ionizing radiationand the influence of cysteamine

D. Benova, G. Kiradzhiev, M. Nikolova(Sofia, BG)Comparative studies on radioprotective and antimutagenic proper-ties of a radioprotective mixture, ATP-AET-serotonin, and the pre-paration WR 2721

M. Dostal, J. Mend, P. Petyrek(Hradec Kralove, CSSR)Radioprotective studies with a mixture of cystamine (C) and 5-me-thoxytryptamine (M)

A. Sverdlov, G. Kalmikova, N. Nikanorova, S. Timoshenko(Gatchina, USSR)A radiomodifying effect of hypoxia and hypoxic protectors followingfast neutron irradiation

COFFEE BREAK

P. Kuna(Hradec Králové, ČSSR)Comparison of toxic and radioprotective effects of cystamine withgammaphos (WR-2721)

R. Kljajič, Z. Milosevic, Emilija Horšiá(Sarajevo, Yu)Protective effect of cystaphos (WR-638) in semilethally irradiatedgoats

E. D. Plotnikova, M. Kh. Levitman, V. V. Shaposhnikova, Yu. V. Ko-shevoy, L. Kh. Eidus(Pushchino, USSR)The radiomodifying effect of gammaphos (WR-2721) on late da-mage in locally irradiated rat brain

K. Schweitzer, Gy. Benkó(Budapest, H)Study of WR-2721 in rats with different types of experimental ulcer

T. Pantev, J. Mircheva(Sofia, BG)Selective radio protection and radiopotentation of normal and ma-lignant tissues of mice

L. Mandel, F. Moravek(Praha, Hradec Králové, ČSSR)The effect of peroral antibiotics and cholestyramin on the intestinalepithelium repair after local irradiation in rats

WEDNESDAY MORNING - AUGUST 28, 1985

Poster sessions

11 a.m. — 1 p.m.

DNA damage and repair

Chairman: M. SkalkaVice-Chairman: J. Matyasova

M. Lokaji'cek(Praha, CSSR)Inactivation mechanism in cells irradiated by gammas and neutrons

J. Barilla, M. Lokajfcek(Deem. Praha. CSSR)Formation of DNA breaks at different oxygen concentration

I. Pridal(Olomouc, CSSR)The modifying role of oxygen in the process of radiation-inducedDSB formation

S. Kozubek, E. A. Krasavin, K. G. Amirtayev(Dubna, USSR)The role of DNA repair in realisation of oxygen effect in differentmutants of escherichia coli

F. H. Yew, P. Y. Yeh, L.M.Chang(Taiwan, ROC)Sodium arsenite induces DNA strand breaks and inhibits DNA re-pair

E. Janovska, J. Pillich(Brno, CSSR)Adaptive repair of E. coli dameged by alkylating agents

L. Ryznar, V. Drasil(Brno, CSSR)Survival of D. radioproteolyticus and E. coli Hfr H following hydro-gen peroxide application

T. A. Sinelshchikova, G. N. Lvova, N. N, Shonija(Moscow, USSR)Disorders of repair of DNA damage induced by gamma-radiationand radiomimetics

G. P. Aptikaeva, E. E, Ganassi, S. I. Zaichkina, O. M. Rozanova(Pushchino, USSR)The relation between damage and repair processes observed onthe molecular and cytogenetic levels in ^-irradiated fibroblasts ofChinese hamster

J. Matyasova, M. Skalka(Brno, CSSR)Chromatin degradation in irradiated thymus - attempts to separatethe damaged thymocyte population

W. Schraeder(Wien, A)Changes of lymphocytes after irradiation measured by light scat-tering in a flow cytometr.

E. Rotreklova, L. Benes(Brno, CSSR)Temperature kinetics of the replicative and unscheduled DNA syn-thesis: Estimation of Qio and Eact

J. Hofmanova, V. Spurna(Brno. CSSR)Repair of X-irradiated mouse cells in heterokaryous and synkary-ons

J. Brozmanova, B. I. Synzynys(Bratislava, CSSR; Obninsk, USSR)Effect of 5-fluorodeoxyuridine on DNA replication and survival inultraviolet-irradiated HeLa cells

T. V. Kirillova, Yu. M. Rosanov(Leningrad, USSR)Effects of UV-irradiation on the cell cycle in Chinese hamster cellswith different UV-sensitivity

Z. Hradecna, L. Kittler(Brno, CSSR; Jena, GDR)Photobiology of furocoumarins and their interference with the de-velopment of bacteriophage lambda

J. Fidy. K. Toth, A. Fekete, G. Csik, K. Feher(Budapest, H)Dark and photochemical binding of furocoumarins to RNA- andDNA-nucleoproteins

A. Gaziev, V. Bezlepkin, Y. Malinovsky, V. Velcovsky(Pushchino, USSR; Brno, CSSR)The preferential initiation of unscheduled DNA synthesis at thenuclear matrix of irradiated cells

Ch. Liicke-Huhle. P. Herrlich(Karlsruhe, FRG)Radiation-induced amplification of viral DNA sequences integra-ted in the genome of Chinese hamster embryo cells

I. Kalina, Gh. Deknudt, A. Leonard, H. Konecna(Kosice, CSSR;MoI, B)Chromosome radiosensitivity in various mammalian species

M. Kreiss, C. Khan-Baumstark, H. Rink(Bonn, FRG)Restriction analysis of rDNA from giant cells (Saccharomyces uva-rum) grown after X-irradiation

F.-P. Bauer, C. Khan-Baumstark, H. Rink(Bonn, FRG)Giant cell formation in X-irradiated cells of wild type and radiationsensitive yeast strains

B. Dimitrov(Sofia, BG)Effects of gamma radiation and 5-bromodeoxyuridine on the fre-quency of sister chromatid exchanges in crepis capillaris

TS. Marinova, V. Tenchova, T. Pantev(Sofia, BG)Replicative and reparative DNA synthesis in peripheral leukocytesfrom gamma irradiated rats

Poster sessions

11 a.m. — 1 p.m.

Varia

Chairman: W. H. MullerVice-Chairman: J. Vacha

J. De Doncker, A. C. Dusaucy, B. Tilquin(Louvain-la-Neuve, B)Radiolysis of amides: Structural effects in pure and aqueous liquidstate

A. Plonka, D. Metodiewa(Lodz, P)Radiation effects in gels: Low- temperature ESR studies on reac-tions of copper-metalloproteins with water radiolysis products

J. Slawinski, L. Ciesla, D. Slawinska(Cracow, Poznari, P)The protective effect of melanins against the UV-induced degra-dation of metallo-porphyrins

E. A. Preoteasa, N. Grecu, V. V. Grecu, A. Enulescu, M. Mocanu(Bucharest, R)Comparative spin-label study of tritiated water-beta irradiated andartificially aged albumins

K. Modos, S, Gaspar, Gy. Ronto(Budapest, H)Comparison of chemical and UV mutagenic activity quantitativephysical characterization

M. Uralova, N. Patzeltova, F. Havlik(Bratislava, CSSR)The influence of the irradiation regime upon the inactivation ofmycotoxins under experimental conditions

L. A. Murtazaeva, D. Kh. Khamidov, V. D. Makarlcin(Tashkent, USSR)H3-cortisol-binding macromolecules in the developing chicken em-bryos tissues

L. D. Szabo, G. Thuroczy, G. Kubinyi, M. Bodo, T. Predmerszky(Budapest, H)Study of biological effects of microwave irradiation on rats

J. Namenyi, A. Gachalyi, L. P. Varga(Budapest, H)Retention of U4Ce in rats with different severity of emphysema

J. Namenyi, A. Gachdlyi, L. P. Varga(Budapest, H)Evaluation of lung defense mechanism in rats with emphysemaafter 144Ce inhalation

F. Zolzer, J. Kiefer(Giessen, FRG)Can action spectra for inactivation and mutagenesis in Chinesehamster cells by used to predict the effects of polychromatic ra-diation?

G. A. Sagatova, A. K. Mirakhmedov(Tashkent, USSR)Subcellular distribution of [3HJ - fluomethuron in rats organs

P. Brunner, G. Bakas, O. Bobleter, W. Ambach(Innsbruck, A)Optical multichannel analyzer for the detection of the light-emis-sion spectra of thermoluminescence material

P. Brunner, A. Gotwald, G. Bonn, W. Albach, O. Bobleter(Innsbruck, A)Computer controlled growth chamber for the production of C-14labelled plants

N. Norbayev, Z. Norbayev(Termez. USSR)Mechanisms of radiostimulation of plants

LeXuan Tu, Dang Van Hanh(Hanoi, SRV)Effect of low doses of -rays on growth of maize and soya-bean

J. Kwapulinski, J. Sarosiek(Wroclaw, P)Impact 137Cs to limiting lake

W. H. Muller(Neuherberg, FRG)Prospects on removability of radio-alkaline earthes by cryptands

E. Beda(Szczawnica, P)Continued research on the development of corn and vegetablesafter previous growth irradiation emitted by short wave diathermy

K. Volenec, M. Juki, A. Mich!, I. Vodicka, B. Ramert(Hradec Krdlove, CSSR)The temperature changes in rabbits after temporary oclussion ofurinary bladder arteries during thermoradiotherapy

THURSDAY MORNING - AUGUST 29, 1985

9 - 12.30

Hall A: DNA damage and repair lit

Chairman: H. JungVice-Chairman: J. Keprtova

N. P. Sirota, A. I. Gaziev(Pushchino, USSR)Studies of firmly bound DNA-protein complexes in irradiated mam-malian cells

V. Velcovsky, V. G. Bezlepkin, Yu. Yu. Malinovsky, A. I. Gaziev(Brno, CSSR; Pushchino, USSR)Preferential initiation of unscheduled DNA synthesis on the DNAfragments associated with nuclear matrix

K. Regel(Dresden, GDR)Certain patterns of DNA double-strand breaks in membrane atta-ched superstructure units cause cell inactivation

M. Berger, J. Laval, J. Cadet(Grenoble Cedex, Villeujuif Cedex, F)Effects of sulphydryl agents on the radiation-induced decompo-sition of nucleic acids and related nucleosides

M. Edgren(Stockholm, S)Effect of dithiothreitol on the radiation induced DNA breaks in

human cells with different intrinsic glutathione content

COFFEE BREAK

D. Frankenberg, M. Kistler, F. Eckardt(Frankfurt, Neuherberg, FRG)Influence of endogenous glutathione content on the induction andrepair of DNA double-strand breaksM. Frankenberg-Schwager, D. Frankenberg, R. Harbich(Frankfurt, FRG)The effect of cysteine on the yield and repair of radiation-inducedDNA double-strand breaks in yeast

M. Korbelik, J. Skrk, A. Suhar, P. Schauer, D. Petrovic, V. Turk(Zagreb, Ljubljana, Yu)The effects of proteinases, their inhibitors and interferons on repairof radiation-induced potentially lethal damage

V. Slezarikova, M. Sedliakova(Bratislava, CSSR)Occurrence of alkali-labile sites in puise labelled DNA of E. coliafter the action of DNA damaging chemicals

L. S. Barenfeld, N. M. Pleskach, V. N. Bil'din, V. V. Prokofleva, V. M.Mikhelson(USSR)Radioresistant DNA synthesis in cells of patients showing increa-sed chromosomal sensitivity to ionizing radiation


9 - 12.30

Hall 8: Modification of radiation effects II

Chairman: V. G. KondratenkoVice-Chairman: K. Volenec

A. H.W. Nias(London, UK)Effect of hypothermia on radiosensitization

F. Koch, F. Kamprad, I. Buchholz(Leipzig, GDR)The influence of hypoxic conditions on the immunologic reactionand phagocytic activity of blood cells after whole body irradiationof swine with 2.0 Gy

I. Rupova, D. Benova(Sofia, BG)Mutagenic effect on mouse somatic cells from single or combinedexposure to radiation and cyclophosphamide

A. Bara, I. Mustea, I. Kindein, R. Gopsa, C. Vladescu(Cluj-Napoca, Bucharest, R)Radiobiologic effect of vladilrad (VR) on Ehrlich ascite tumor cells

A. A. Turdiyev, R. B. Usmanov(Tashkent, USSR)Modification of radiation effect by the spleen extract of the turtle(Testudo Horsfieldi)

P. Salovski, H. Nechev, V. Shopova, Ts. Shopova(Pleven, BG)Specificity of the lung damage after combined application of for-maldehyde and external ionizing radiation

COFFEE BREAK

B. A. Auerbach, A. K. Gajewski, M. Lenarczyk, M. G. Slowikowska(Warsaw, P)Teratogenic effects in mice exposed to single dose of X-rays andprolonged administration of caffeine during pregnancy

D. Rotkovska, A. Vacek, A. Bertonickova(Brno, CSSR)Use of microwaves for modification of radiation damage in mice

S. Sundell-Bergman, K. J. Johanson, S. Richter(Uppsala, S)Enhanced radiation damage to ionodeoxuridine-labelled cells afterirradiation with 137Cs-gamma- or soft X-rays

I. Turai(Budapest, H)Evaluation of effectiveness of stable iodine prophylaxis comparingdata of animal experiments and of computer simulations

THURSDAY MORNiNG - AUGUST 29, 1985

9 - 12.30

Hall C: Pathophysiology of radiation damage I!

Chairman: Mrs. E. HorsicVice-Chairman: J. Pospfsil

M. Beauduin, J. Gueulette, B. M. de Coster, 5. Vynckier and A.Wambersie(Bruxelles, B)RBEn.n of neutron beams produced by 34, 45, 65 and 75 MeV pro-tons and by 50 MeV deuterons for intestinal crypts regeneration

G. R. Morgan, C. J. Roberts(Oxon, U. K.)The RBE of 24 keV neutrons for V79 AH1 cells

G. K. Hagemann, C. Lipfert, G. Wuppen(Hannover, FRG)Responses to sublethal damages of CHO-cells in colony size dis-tributions

M. Arnold, J. Kummermehr(Neuherberg, FRG)A new model to investigate bone healing in mature bone aftersingle and fractionated X-irradiation

L. Bertok, S. U. Nagy(Budapest, H)Effect of irradiation on serum Ti level and response of thyroid glandto exogenous TSH in rats

D. Radulescu, St. Imreh, Elisabeta Fazakas(Cluj, Napoca, R)Chromosome aberations and micronuclei as a tool for the genetic

councelling in medical radiology

COFFEE BREAK

M. Zwitter, M. Kalisnik, M. Logonder-Mlinsek(Ljubljana, Yu)Functional state of the rat thyroid gland determines its radiosen-sitivity

P. Mirkhamidova, S. K. Khalikov, L SH. Rabinovich(Tashkent, USSR)Effect of roentgenization on rat liver nuclei and mitochondria afterhepatectomy

G. M. Obaturov(Obninsk, USSR)Mutation formation and mammalian cell inactivation by heavy char-ged particles

A. Vaglenov, V. Manchev(Sofia, BG)Univalents and fragments in mammalian meiosis

A. Vaglenov, A. Bajrakova (Bulgaria), E. Fedorenko, A. Kabachenko(Sofia, BG); Moscow, USSR)RBE of 9 GeV/nucleon proton radiation

A. Vaglenov, I. Baev(Sofia, BG)Species specific features of reciprocal translocations induced byspermatogonial irradiation in mammals

P. Jacquet and S. Grinfeld(Mol, B)Studies of the ability of different factors to modify the radiosensi-tivity of the early mammalian embryo


Poster sessions:11 - 12.30Dosimetry, LET, RBE

Chairman: J. JankowskiVice-Chairman: Z, Prouza

B. Nowak, J. Jankowski(Lodz, P)Results of individual dosimetry in Poland

I. Burian, J. Cech, M. Richter, A. Smid(Pnbram, CSSR)Individual Monitoring of Radon Daughters Intake

J, Jankowski, P. Swiderski(Lodz, P)Estimation of life-time dose in persons exposed occupationally toX-raysM. A. Staniszewska, J. Jankowski(Lodz, P)Absorbed dose received by patients subjected to radioisotopic invivo procedures

M. A. Staniszewska, J. Jankowski(Lodz, P)Absorbed dose received by children subjected to X-ray examina-tionsM. Mileva, M. Bulanova, I. Georgieva, B. Ivanov(Sofia, BG)Chromosomal anomalies in bone-marrow cells of rats exposed tohelium nuclei.M. Bulanova, M. Mileva, I. Georgieva, B. Ivanov(Sofia, BG)Cytogenetic effect following exposure of human lymphocytes tohelium nucleiE. E. Ohanjanian, A. A. Ohanjanian(Yerevan, USSR)The dosimetry of the ionizing radiation by densito-geometrical pa-rameters of lymphocytes

F. Spumy, I. Votockova(Praha, CSSR)Response of air-filled ionization chambers in neutron-gammabeamsF. Podzimek, et al.(Hradec Kralove, CSSR)The possibilities of biological object irradiation at Czechoslovakneutron sourcesM. Pesek, Z. Prdsil, M. Rerichova, V. Spevacek, J. Simek(Praha, CSSR)Dosimetric systems used for routine irradiation of biological ma-terials

A. Danckova, K. Vacek(Praha, Rez, CSSR)Alanine based dosimetry - experience and application

Effects of low doses, late effects of irradiation

Chairman: B. ReubelVice-Chairman: L. Tkadlecek

A. Pikulev, I. Khripchenko, V. Lavrova(Minsk, USSR)Low dose ionizing radiation on pyridoxa! enzymes content in ratbrain

I. Datelinka, I. Ahlers, M. Toropila(Kosice, CSSR)Effect of continuous irradiation on some enzymes of biosynthesisof fatty acids in rat liverS. Viklicka, L Tkadlecek, M. Hofer, Z. Karpfe!(Brno, CSSR)B. S. Fedorenko, R. A. Kabicyna, A. N. Kabachenko(Dubna, USSR)Morphology of rat hemopoietic tissue one year after whole-bodyirradiation with high-energy (4 GeV/nucIeon, 4 Gy) helium ionsK. Hyrc, K. Cieszka(Cracow, P)Modification of late postirradiation changes in electrophoreticpattern of Bomirski hamster melanoma (BHM) by irradiation con-ditions

M. Hofer, L. Tkadlecek, S. Viklicka, Z. Karpfel(Brno, CSSR)B. S. Fedorenko, R. A. Kabicyna, A. N. Kabachenko(Dubna.USSR)Morphology of rat hemopoietic tissue one year after whole-bodyirradiation (dose of 4 Gy) with 6(JCo gamma rays

B. Reubel, F. Steinhdusler(Salzburg, A)Effects of low doses of gamma irradiation on the extracellularoxygen consumption of WI38 lung fibroblasts

P. M. Eckl(Salzburg, A)Low-level gamma- and neutron-irradiation effects on vicia fabagrowth and cell division

N. E. A. Crompton, F. Zdlzer, E. Schneider, J. Kiefer(Giessen, FRG)Increased mutant yield on low dose-rate ^-exposure of Chinesehamster cells

L. P. Varga, S. Gundy, J. Namenyi, I. Szegedi(Budapest, H)Mutability and radiosensitivity of cultured Chinese hamster ovarycells exposed to low dose rate of tritium beta radiation

K. N. Nishanbaev, Ju. V. Shpoljansky, G. I. Allajarova, R. Z. Rusta-mova(Tashkent, USSR)The effect of small doses of irradiation on lymphocyte receptorsof Chicken embryos

J. Pospisil, J. Vlaskova, P. Pouckova, .1. Polivkova(Praha, CSSR)The effect of whole-body irradiation on the occurrence of chemi-cally induced tumors of inbred mice with different activabilitiesof the AHH-system

D. Kh. Khamidov, K. N. Nishanbaev, Ju. V. Shpoljansky, T. V. Pota-pova, A. V. Andreev(Tashkent, USSR)The effect of small doses of irradiation on AFC and cAMP of spleenin chicken ontogenesis.

THURSDAY AFTERNOON - AUGUST 29,1985

2 - 4 p.m.

Hall A: 2 - 3 p.m. Tumour irradiation III

Chairman: E. MagdonVice-Chairman: A. Vacek

M. Niisse and S. B. Curtis(Berkeley, Ca, USA)Micronucieic induction after heavy ion irradiation in a rat rhabdo-myosarcoma in vitro and in vivo using a monoclonal antibody toBrdUrd and cell sorting

A. J. Mill(Berkeley, Glos.. UK)The response of mammalian cells to 24-KeV neutrons: The rele-vance to radiation protection and neutron capture therapy

C. Biagini, F. Campodonico, S. Giannini, F. Vitelli(Rome, I)Radiation effect on CNS in NMR image

T. Kubasova, G. J. Koteles, L. Simbirtzeva, V. F. Mus, E. A. Zherbin,K. P. Hanson, I. Sinkovics, Zs. Karika(Budapest, H; Leningrad, USSR)Lectin-binding by blood cells of radiotherapy patients and dose

assessments

COFFEE BREAK

Hall A: 3 - 4 p.m. Dosimetry, LET, RBE II

Chairman: J. W HansenVice-Chairman: F. SpurnyT. Niewiadomski, M. Jasinska, P. Wasiolek(Krakow. P)Weak points of dose assessment models due to release from coalpower plants

J. Jankowski, H. Mikolajewska(Lodz, P)Relationship between surface exposure dose and effective doseequivalent

E. Horsic, R. Kljajic, Z. Milosevic(Sarajevo, Yu)Bio-dosimetric evaluation of radiation lesions in experimentallyirradiated goats

F. Spumy(Praha, CSSR)Depth-dose studies in relativistic charged particle beams withpassive detector


2 - 4 p.m.

Hall B: Effects of low doses

Chairman: L. SztanyikVice-Chairman: I. Ahlers

L. E. Feinendegen(Jiilich, FRG)Biological effects of low doses of radiation

L. B. Sztanyik(Budapest, H)What is a low dose in radiological sciences?

Ju. G. Grigoriev(Moscow. USSR)Effects on animals due to low doses chronic exposure to ionizingradiation for years

I. Ahlers, E. Ahlersova, A. Molcanova, M. Toropila, I. Datelinka,B. Smajda, M. Praslicka(Kosice, CSSR)Bone marrow lipids in continuously irradiated rats

Z. Pietrzak-Flis, I. Radwan(Warsaw, P)Consequences of lifetime tritium exposure for postnatal develop-ment of rats

J. Juraskova, V. Drasil(Brno, CSSR)Changes in repair ability of continuously irradiated cells

COFFEE BREAK

J. Gidali, I. Feher, B. Kanyar(Budapest, H)Growth kinetics of haemopoietic stromal precursors after low dosegamma irradiation

H. Bazin, B. Platteau, G. Pinonlataillade. J. Maas(Brussels, B; Fontenay aux roses, F)Studies on long term continuous irradiations on the B lymphoidsystem of the rat

I. Petku, T. Birsan, F. Tripadus, N. Mocanu(Bucharest, R)Chronic, low loevel tritium contamination effects on 125IUdR incor-poration in DNA

A. Pikulev, M. Sholukh(Minsk, USSR)Adrenergic regulation of asparate aminotransferase isozymes ac-tivity under low doses of X-rays


2 - 4 p.m.

Hall C: Pathophysiology of radiation damage III

Chairman: O. Vos

Vice-Chairman: V. Kamarad

TH. Herrmann, L. Voigtmann, A. Knorr, J. Lorenz, K. Welker, M. Jo-hannsen(Dresden, GDR)Fractionated neutron and photon irradiation in the right lung ofyoung pigs

A. M. Dancewicz, M. M. Jeleriska(Warsawa, P)Effect of whole body irradiation of rats on collagenolytic activityin their lungs

S. A. Chepurnov, N. E. Chepurnova, U. V. Likhachev(Moscow, USSR)Primary acute effects in the cortex and limbic system of the braininduced by laser irradiation of the brain of the rat

V. Kamarad(Olomouc, CSSR)Ultrastructural and histochemical changes in rats after supralethalgamma-irrad'ation

COFFEE BREAK

M. Resl, M. Dostal(Hradec Kralove, CSSR)Gastrointestinal radiation injury of supralethal single gamma-ir-radiated dogs: A morphologic observation

N. Visheva, St. Milanov, B. Ivanov, I. Kurtev(Sofia. BG)Time and dose dependant changes of the function of rat pituitary--gonadal axis after single-shot irradiation with low and high dosesgamma rays

M. Moldavsky(Samarkand, USSR)The postnatal development of the adrenal gland after in utero andin progenesis irradiation

E. Paulikova, M. Toropila, E. Ahlersova(Kosice, CSSR)Radiation dose-response of some gluconeogenic and adaptiveenzyme activities of rat liver


2 - 4 p.m.

Poster sessions:

Tumour irradiation

Chairman: Mrs. E. SirackaVice-Chairman: Mrs. E. Misurova

K. Cieszka, M. Kapiszewska, R. Gurbiel, K. Hyrc(Krakow, P)Comparison of the lethal effects of X-irradiation at 0cC in me-lanoma and CHO cells in vitro

A. Gachalyi, J. Namenyi, L. P. Varga(Budapest, H)Effect of mixed ligand chelate therapy on the reduction of niobiumand cerium in mice

K. Hyrc, K. Cieszka(Krakow, P)The effect of ionizing radiation on electrophoretic profiles of me-lanoma cells growing in vivo

S. Kozubek, P. Vodvarka(Paskov, CSSR)A correction of the NSD conception (NSD)

T. Majle, A. K. Gajewski, M. Krzyzanowski, M. G. Slowikowska, Z.Rozycki(Warsaw, P)Diagnostic radiation and adult leukemia. The results of case —control study in Poland

1.1. Pefevina, N. A. Gulverdashvili, G. G. Afanasiev(USSR)Hypoxic cells in tumours - is the critical population for radiothe-rapy?

P. Vodvarka, S. Kozubek(Paskov, CSSR)Thoracic spinal cord tolerance irradiation schedules

G. Wolf, R. Kammerer, H. Fender(Berlin, Magdeburg, GDR)Cytogenetic investigation in patients after irradiation of the shoul-der-joint

Radiation Hematology

Chairman: M. QuintilianiVice-Chairman: V. Kofranek

L Tkadlecek, M. Hofer, S. Viklickd, Z. Karpfel(Brno, CSSR)Growth and differentiation dynamics in mouse exogenous spleencolonies

F. Hauser, E. Necas(Praha, CSSR)Simulation of the postirradiation damage of a stem cell population

L. Sefc, M. Krsek, E. Necas(Praha, CSSR)Postirradiation dip in stem cell numbers in mice pretreated withcyclophosphamide

M. Pospisil, J. Netikova, A. Kozubfk(Brno, CSSR)Enhancement of postirradiation hemopoietic recovery in mice byindomethacin treatment

A. Kozubik, M. Pospisil, J. Netikova, J. Jary(Brno, Praha, CSSR)The effect of /3-(1 -* 3)-D-glucan on hemopoietic recovery in lethallyirradiated and bone marrow transplanted mice

M. Beno, D. Piknova, A. Hrabovcova, L. Batorova(Bratislava, CSSR)Stimulation of lymphocytes by specific bacterial antigens after neu-tron irradiation

E. Misurova, J. Gabor, K. Kropacova, D. Pado(Kosice, CSSR)Effect of ionizing radiation on DNA-synthesizing cells of blood

A. Molcanova, I. Ahlers(Kosice, CSSR)Influence of single total body gamma radiation on cellularity andlipids in bone marrow of rats

A. Sedlakova, J. Timko(Kosice, CSSR)The role of lipids in bone marrow and thymus of irradiated rats

J. Siiliovd, N. Mackova, M. Hvizdosova, E. Misurova(Kosice, CSSR)Effect of cyclophosphamide on hemopoietic organs in rat. Chan-ges in DNA and basic proteins

N. Mackova, J. Siiliova(Kosice, CSSR)Effect of cyclophosphamide on hemopoietic organs in rat. The mor-phological changes

M.Solle(Berlin, GDR)Radiation-induced changes of toluidine blue uptake and glycerollysis time in erythrocytes

M. Tatara, K.Tvaroskova(Bratislava, CSSR)Changes in the intrinsic fluorescence of lymphocytes after irradia-tion

FRIDAY - AUGUST 30,1985

9 a.m. — 3 p.m.

ELEG/EULEP Symposium:

Late effect of irradiation

Morning session

Chairman: J. B. Reitan

Vice-Chairman: A. Bayer

K. Neumeister(Karl-Marx-Stadt, GDR)Radiation carcinogenesis

J. R. Maisin(Mol.B)Survival and disease incidence in male BALB/c and C57BL miceafter single, fractionated gamma or d(50)-Be neutron exposure

W. A. Miiller, U. Linzner, E. H. Schaffer(Neuherberg, FRG)Dosimetric conditions for systemic and local induction of osteo-sarcomas by bone-seeking radionuclid?s

V. Dvorak, A. Sedlak, D. Bubenikovd, V. Kofranek(Praha, CSSR)Risk of osteogenic sarcomas in 221Ra or 22GRa mouse experiments

V. Kofranek, V. Svoboda, A. Sedlak, V. Dvorak(Praha, CSSR)Late effects of radium and plutonium in mice

J. Sevc, V. Placek, A. Smfd, L. Stromp(Praha, CSSR; Prfbram, CSSR)Lung cancer risk at low level of radiation exposure

J. Sevc, L. Tomasek, V. Placek, E. Kunz, A. Smfd(Praha, Pffbram, CSSR)Radon daughter cancer in man

J. Sevc, E. Kunz, L. Tomasek, J. Horacek, A. Sedlak(Praha, Karlovy Vary. CSSR)The dose-response relationships in different conditions of radondaughter exposure

S. Hambartzumian, S. Papoyan(USSR)Combined action of small activities of radioisotopes and carcino-gens on the process of tumor induction

V. Klener, R. Tuscany, J. Vejlupkova, J. Dvorak(Praha, CSSR)Long-term follow-up after accidental gamma irradiation from aCo-60 source

M. Ruzdic(Sarajevo, Yu)Longterm effects of occupational exposures to ionizing radiation

M. Burkart(Wurenlingen, CH)An estimate of the lung cancer risk from radon and its decay pro-ducts in alpine owellings

Afternoon session

Chairman: E. KunzVice-Chairman: V. Dvorak

A. Bayer(Presov, CSSR)Significance of differences in late pathology of irradiated Wistarrats

VI. Svoboda, A. Sedlak, Z. Kotaskova(Praha, CSSR)CFU-S surviving under the long-term contamination with plutoni-um-239

J. B. Reitan, K. Feren(Oslo, N)Scanning electron microscopy of the irradiated mouse bladderurothelium

C. Michel, R. Babini, Hedi Fritz-Niggli(Zurich, CH)Antagonism between X-rays and cadmium in embryonic mouse de-velopment

K. Chomiczewslci, A. K. Gajewslci(Lodz, Warsaw, P)Late pathomorphologic changes in the testes of mice after X-irra-diation with sublethal doses at different ages

M. Lenarczyk, B. A. Auerbach, M. G. Slowikowska, A. K. Gajewski(Warsaw, P)The effects of neonatal X-irradiation on reproduction of femalemice

Z. Major(Warsaw, P)Tritium in organic compounds of brain of rats exposed to tritiatedwater or tritiated food during three succesive generations

STAND-BY PAPERS

U. Andreozzi, L. Addis, M. Garbati, A. Lori, A. Minnucci, M. Castori-na(Roma, I)Metabolic behaviour of plutonium in mice

I. G. Borisova, E. V. Boudnitskaya(Moscow, USSR)Lipoxygenases in modification of plant radiation damageI. G. Borisova, E. V. Boudnitskaya, G. L. Shaposhnikov, V. V. Shoubin(Moscow, USSR)Effect of lipoxygenases molecular organisation on their radiationinactivationS. E. Cabrielian, S. A. Badjinian, S. E. Hakopov, A, A. Kharatian(Erevan, USSR)Some mechanisms of the radioprotector effects of cistaminJ. Gueulette, M. Beauduin, Y. Galiano de Bula and A. Wambersie(Haine-St-Paul, B)Comparison of the effects of X-rays and fast neutrons on the cycleduration of EMT6 cells. A time-Lapse cinephotomicrographic studyAt. Imreh, C. Vladescu, Adela Bara, Piroska Imreh(Cluj-Napoca.R)Chromosomal radiosensitisation of normoxic and hypoxic ceils bymisonidazole, vladilrad and other electronaffinic compoundsL. I. Kharchenko, T. E. Paviovskaya(Moscow, USSR)Cysteine protection against the radiation induced binding of oxy-gen to enzyme molecules in solutionA. K. Mirakhmedov, M. M. Djuraeva, D. Kh. Kharnidev(Tashkent, USSR)Effect of irradiation on protein and lipid composition of nuclearand mitochondrial fractions of rabbit embryo liver

Nguyen Huu Dong and MakedonovG. P.(Hanoi, Vietnam; Moscow, USSR)Photosensitization to near-ultraviolet light by 8-methoxypsoralenin the Chinese hamster cells in vitro

Nguyen Kim Hai(Hanoi, Vietnam)The use of gamma rays in rice breeding for cold tolerance

Z. Paskalev. !. Pejankov, E. Hadjidekova(Sofia, BG)Conformatiori changes of blood plasma protein macromolecules ofrats after the combined action of !iaSr or 1MCe and Phcsalon

Phan Phai(Hanoi, Vietnam)Effect of radiation at early stages of ontogenesis in plants

Phan Phai and Dinh Luyen(Hanoi, Vietnam)Genetic effect of physical mutagen in soybean

Phan Phai, Tran Duy Quy and VU due Quang(Hanoi, Vietnam)The use of gamma radiation in breeding and improvement of rice

Phan Phai and Tran Duy Quy(Hanoi, Vietnam)Effects of low doses radiation of gamma rays on growth and deve-lopment of cultivated rice

L. Z. Polishchuk, Y. G. Timoschenko(Kiev, USSR)Morphometric study and evaluation of heterogeneity of some indi-ces of endometrium hyperplastic process and cancer

S. Stoev, Yu. B. Kudryashov(Sofia, BG; Moscow, USSR)Effects of AET and its relative or analogical compounds on the levelof endogeneous radiosensitizer

A. Valeanu, St. Imreh, Z. Uray, M. Covalcic(Cluj-Napoca, R)Combined action of leucotrofina, radiation and anticancer drugson chromosomes and micronucleiS. Jednorog,B.Lazaska(Warsaw, P)Experimental determination of (d, n) neutron's dose distribution inratsO. Makiejev(Sverdlovsk, USSR)Metabolic modification of haemopoesis damage during radiationdisease

m

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I9th

A B S T R A C T S

EUROPEAN SOCIETY FOR RADIATION BIOLOGY

19th ANNUAL MEETING

PRAGUE, AUGUST 26 - 30,1985

This volume contains all abstracts of papersaccepted till MAY 15th, 1985 by the ScientificCommittee. These abstracts are photographicalyreproduced from the original forms submittedby the authors. The authors are responsiblefor the content and the grammatical style oftheir abstracts. The papers are arranged inalphabetical order of the author's names.

1

BONE MARROW LIPIDS IN CONTINUOSLY IRRADIATED RATS

I. AHLERS. E. AHLERSOVA. A. MOLCANOVA. M. TOROPILA,

I. DATELINKA. B. §MAJDA. M.

Institute of General Biology, P.3. Safdrik Univer-

sity, KoSice, CSSR

The lipid composition of bone marrow was inves-

tigated mainly in single whole-body irradiation of

rats; there was a lack of data on lipid changes of

bone marrow in continuously irradiated animals.

Male SPF bred Wistar rats of average weight 200

g were irradiated continuously with daily dose 0.19

Gy (up to 120 days), 0.57 Gy (90 d) and 0.96 Gy (35

d) of gamma rays from Co source. The concentrati-

on of trlacylglycerols (TG) and phospholiplds (PL)

were determined in the bone marrow (femur) hoaoge-

nates. TG began to increase within d 21-30 in 0.19

Gy, within d 7-14 in 0.57 Gy end within d 3-10 in

0.96 Gy daily exposure; the accumulation of TG per-

sisted till the death of animals. Parallelly with

TG increase a decrease of PL concentration was ob-

served. The linear correlation between TG increase

and PL decrease in bone marrow was noted in 7-d

continuously irradiated rats with daily doses ran-

ged between 0.55 - 2.74 Gy of gamma rays.

2

THYROID HORMONfcS IN IRRADIATED RATS

E. AHLERSOVA. I. AHLERS. M. TOROPILA. I. PATELINKA

Institute of General Biology, Safarik University,

KoSice, CSSR

The role of thyroid hormones in the development

of radiation damage was not yet elucidated, especi-

ally in continuously irradiated animals.

The concentration of thyroxine (T4), triiodothy-

ronine (T,) and reverse triiodothyronine («"T,) was

determined in serum of male Wistar rats, whole-body

irradiated with single lethal (14.35 Gy) or nonlet-

hal (2.39 Gy) dose of X rays and in rats irradiated

continuously with gradjd daily doses of gamma rays.

The decrease of T. and T, levels in the early

period was noted in lethally X irradiated rats;

there was an increase of rT, in the terminal pe-

riod. In nonlethally X irradiated rats only an iso-

lated decrease of T, level in the early period was

observed. The continuous irradiation with high dai-

ly dose (0.96 Gy,35 days) resembled essentially the

changes in lethally X irradiated rats. Medium (0.57

3y,90 d) and low (0.19 Gy,120 d) daily doses of coo

tinuous gamma irradiation caused unambiguous incre-

ase of T, level and less marked decrease of rT_ le-

vel; T. values changed irregulary and less signi-

ficant.

FREQUENCY OF MICRONUCLEI IN X-IRRADIATED HUMANLYMPHOCYTES

2su2sanna ALMASS Y, B.KANYAR, G.J. KOTELES

"Frederic Joliot-Curie" National Research Institutefor Radiobiology and Radiohygiene, H-1775. Budapest,Hungary

Micronucleus frequency in human peripheral lvmpho-cytes x-irradiated in vitro /200 kV,20mA,l mm Cufilter, source target distance 60 cm, 0,317 Gy.min"^-/with doses 0,25, O,5, 1,2,3 and 4 Gy were determined.Cells stimulated by PHA were incubated for 48,72 and96 hours. The 72 hours time point proved to be opti-mal as there was only a slight further increase ofnumber of micronuclei between 72 and 96 hours. Thehypotonization was made by 0,075 M KC1 and thestaining by 0,05 per cent acridine orange solutions.Introducing fluorochrome staining for human lvmpho-cytes resulted in a safe and easy identification ofthis aberration. Counting of micronuclei was perform-ed by fluorescence microscopy. Dose-effect relation-ships were determined from lymphocytes of 3 health^male donors of 20 years of age, separately. Duplicatecultures from each donor were run, altogether 6000cells were scored. By statistical evaluation the datawere best fitted to linear-quadratic /Y=c+<iXy+fiD^/dose-effect relationship, where the values for c,efcand/iper 1000 cells were 3,97±3,O7, 51,1+11,1,13,4+3,5, respectively.

4THE RELATION BETWEEN DAMAGE AND REPAIR PROCESSESOBSERVED ON THE MOLECULAR AND CYTOGENETIC LEVELS IN^-IRRADIATED FIBROBLASTS OP CHINESE HAMSTER

G.P.APTIKAEVA, E.E.GANASSI, S.I.ZAICHKINA,O.M.ROZANOVA

Institute of Biological Physics, Acad.Sci.USSR,Pushchino, USSR

The processes of damage and repair on the molecu-lar and cytogenetic levels in the^-irradiated fib-roblasts of Chinese hamster were compared in orderto determine the molecular target of chromosomalmutagenesis. The kinetics of the repair of cytoge-netic aberration of chromosomes was studied usingpreliminary condensation and modification of radia-tion damage* The damage- and repair of DNA were stu-died by alkali unwinding and further separation ofsingle- and double-stranded DNA on hydroxylapatiteas well as by the fluorescent method that we havedeveloped in order to determin DNA lesions in an in*dividual cell. The results obtained showed that theamount of anchor DNA in a cell correlates well withthe amount of unrepaired DNA lesions which initiatestructural chromosome aberrations. This allows fora suggestion that the anchor DNA is the target forchromosomal mutagenesis.

A NEW MODEL TO INVESTIGATE BONE HEALING IN MATURE BONEAFTER SINGLE AND FRACTIONATED X-IRRADIATIONM. ARNOLD J.KUMMERMEHR

Gesellschaft fur Strahlen- und Umweltforschung,D-8042 Neuherberg, F. R. G.

To inflict a standardized bone defect a hole 1.2 mm indiameter was drilled into the diaphysis of each femur of3-4 months old Wistar rats and its subsequent osseoushealing was examined. Bones were removed four to eightweeks after surgery, embedded in methacrylate and sect-ioned serially. The amount of newly formed bone wasquantified by morphometric methods and expressed as per-centage of the entire hole. In control animals the defectwas found nearly closed after eight weeks. Irradiatingthe bone 24 hours before surgery with single doses of 10to 15 Gy of 3OO kV X-rays did not compromise healing andrather increased the amount of bone deposition. Afterdoses higher than 15 Gy bone formation decreased as thedose_increased and after 20 Gy no bone formation was seeneven after 8 weeks, yielding a steep dose response curve.A similar radiosensitivity was seen when the interval be-tween irradiation and surgery was increased to 1 week or1 month. To study the fractionation effect in this systemthe following schedules of irradiation were used:2f/5d,3f/5d, 5f/5d and 10f/5d. The doseincrements required toproduce a given decrease in bone formation suggest an &/&of around 6 Gy.

TERATOOElfIC EFFECTS IN MICE EXPOSED TO SINGLE DOSEOF X-RAYS AND PROLONGED ADMINISTRATION OF CAFFEINEDURING PREGNANCY

£g, A.K. GAJEWSKI, M. LENARCZXK, M.Q. SLO-LKvwSl

National Institute of Hygiene, Warsaw, PolandThere ara suggestions that although caffeine at

doaes approximating thoae of high daily consumptionin humans ia not itaalf teratogenic, it may enhancethe taratoganie affect of other agenta i.e. it mayact aa a "coteratogen" (B.A. Kihlman, Caffeine andChromosomes. p.412). This coteratogenic effecta iaknown for single X-ray exposure, however little hasbeen done in the eaae of chronic exposure to caffei-ne.

In thia paper results ot chronic exposure to caf-feine and single X-rays irradiation at the 8th dayof pregnancy ara reported.

Four groups of mice were investigated: control,continuously exposed to caffeine during pregnancy(0*01 % water caffeine solution), irradiated with0.8 Gy at 8th day poatconception and a group exposedto both of these agenta. The experiments was perfor-med according to Wilson (J.G.Wilson, Teratology:Principles and, Techniquea).

Caffeine and caffeine combained with X-rays in-creased a percentage ot dead fetuses: from 5* incontrol group to 8% in both of these groups. Therewaa no differences between all four groups in thenumber of life fetuses per pregnant female, meanweight of the fetus or percentage of fetuaea withexternal malformations of soft tissues. Caffeineand irradiation increased the number of skeletalmalformations. In group exposed to both of theseagenta it was a aynergeatic effect. However, thiseffect was only due to the presence of additionalribs.

HEAVY ION INDUCED DNA STRAND BREAKS AND THEIR REPAIR:DEPEN-DENCE ON LET, PARTICLE ENERGY AND DOSEE. Aufderheide*, H. Rink*, L. Hieber**, G. Kraft**

*Inst. f. Strahlenbiologie, Bonn; **GSI Darmstadt, WestGermany

We have studied the influence of LET and energy of heavycharged particles (8 * Z * 9 2 ) on the induction and repair ofDNA strand breaks in diploid bovine lens epithelial cells invitro using the DNA unwinding technique (Rydberg, 1975, Ra-diat. Res. 61_, 274). The efficiency of strand break inductionwas found to~be linearly related to the kinetic energy of theparticles with little or no influence of LET. RBEs variedfrom 0.02 for 4.1 MeV/u 238-U ions to 0.2 for 19.3 MeV/u 40-Ar ions. Repair was found to be slow witb considerable repairtaking place at even more than 20 h after irradiation. Re-joining of strand scissions was fairly complete: On the rfhole,less than 10 %, sometimes less than 5 %, of the damage re-mained at 22 h post irradiation. Seemingly complete repairwas observed after 19.3 Mev/u 40-Ar irradiation, indicatingan important role of misrepair in the inactivation of cellsby heavy ions. Preliminary results indicate a rather completelack of repair after 4.1 MeV/u 238-U irradiation. In contrastto X-irradiation, a strong dependence of repair kinetics ondose was observed for ions with Z » 18. Taken together, theresults suggest both an increasing complexity of the DNA da-mage with increasing LET and a possible influence of non-DNA-damage. Preliminary'results indicate a relation of single- todouble-strand-breaks of app. 2:1.

8

MEA AND AET STUDIED FOR ANTIMUTAGENIC EFFECTS BYTHE TEST OP MORPHOLOGIC SPERM-HEAD ANOMALIES(MSHA) IN THE MOUSEA. BAJRAgQVA, V. MANCHEVInstitute of Roentgenology and Radiobiology,Sofia, Bulgaria

Frequency of morphologic sperm-head anomalies(MSHA) is a genetically determined trait for a gi-ven inbred mouse strain. Exposures to radiation,chemical and other agents produce an excess overspontaneous MSHA rates. Based on this observation,a test has been developed (Wyrobek et al#, 1983,Mutat.Res., 11 » 1) to detect and characterize thegenotoxic effects of various mutagens in mammals*We have used this test to study the antimutagenicproperties of two established radioprotectiveagents, MEA and AET. The experiments involvedadult F1 (BALB/C x C57B1) mouse males injectedwith 150 mg/kg MEA or 250 mg/kg AET 15 min priorto acute 3-Gy gamma irradiation. MSHA samplingtimes were from 3 to 10 weeks postradiation. Pro-tected animals were found to have reduced levelsof radiation-induced MSHA. With either agent, theextent of radiation protection was dependent onthe spermatogenic stage at which damage inductionoccurred. When administered solely, neither MEAnor AET were noted to produce any genotoxic effectunder the conditions of this study.

f ! •'.

RADIOBIOLOGIC EFFECT OF VLADILRAD (VR) ON EHRLICHASCITE TUMOR CELLSADELA BARAf9I. MUSTEA

1, I. KINDEIN1, RODICA GOFSA2,C. VLADESCIT1* Oncological Institute Cluj-Napoce, Romania2. Chemical-Pharmaceutical Research Institute,

Bucharest, Romania

The radiobiologic effect of romanian productVladilrad (VR) was studied comparatively with Miso-nidazole (Mis) an Ehrlich aacites carcinoma cellsin two experimental models* In both models VR exhi-bited moderate radiosensitizing properties as com-pared with Mis but VR was lees toxic*

10RADIORESISTANT DNA SYNTHESIS IN CELLS OFPATIENTS SHOWING INCREASED CHROMOSOMALSENSITIVITY TO IONIZING RADIATIONLoS.Barenf eld.

Institute of Cytology AS of the USSRInhibition of DNA synthesis by ionizing ra-

diation in normal cells i s part of a cellulardefense mechanism which allows time for DNA re-pair o This mechanism rather than a defect inthe ability to repair damage produced in DNAby that agent has been shown to be defectivein AT, the Nijmegen Breakage Syndrome andZP3HR cells (Painter, Young, 1980, PNAS.77,7315i de Wit et al», 1982, Uutat. Res«,80t221;Taalman et al», 1983, Hut at . Res., 112,23). Inthis work the rate of DNA synthesis after gam-ma irradiation was studied either by analysisof the steady-state distribution of daughter-*H DNA in alkaline sucrose gradients or by di-rect assay of ~H thymidine incorporated intoDNA of fibroblasts derived from normal donor,Down's syndrome (DS), Werner's syndrome andXP (strain XP2LE) patients with chromosomal hy-per sensitivity to ionizing radiation* Doses ofgamma-rays that markedly inhibited the rate ofDNA synthesis in normal cells caused almost nothe inhibition in cells of ttie affected indi-viduals* Radioresistant DNA synthesis in DScells was mainly due to a much less inhibitionof replicon initiation than those in normalcells; DS cells were also more resistant to da-mage that inhibited replicon elongation* Ourdata suggest that radioresistant DNA synthe-sis may be an intrinsic feature of all disor-ders with increased chromosomal radiosensiti-vity.

11

FJR-IAÎOM OF DM BREAKS AT DIFFEREKT OXYGEN

Hospital and policlinic, DeS£n, VInstitute of Physics, 3SA7, Prague, CSSR

Double-strand breaks of chromosomal DM. playa fundamental role in cell inactivatton. Therefore,the role of different agents in DM-break forma-tion could lead to a better understanding of thewhole radiobiological mechanism. Dsb are alwaysrepresented by a pair of ssb formed by one parti-cle of radiation beam in diverse strands of a D Mmolecule. Only parts of densely ionizing particletracks (e.g. ends of electron tracks for scarselyionizing radiation) can give a sufficient probabi-,lity of forming such lesions. An important questi-on concerns then the ratio of different directand indirect processes in break formation. A sim-ple model describing the combined effect of diffe-rent radicals formed by radiation in water soluti-ons has been proposed. The influence of differentoxygen concentrations has been taken into account.The model makes it possible to determine the ratioof different radicals (and of direct effect) inradiation formation od D M breaks if correspondingdata are available. The approach will be exempli-fied by an orientation analysis of experimental-data set representing a qualitative dependence ofdsb numbers on different oxygen concentrations.

12

GIANT CELL FORMATION IN X-IRRADIATED CELLS OF WILDTYPE AND RADIATION SENSITIVE YEAST STRAINSBAUER, F.-P., BAUMSTARK-KHAN, C., RINK, H.

Institute of Radiation Biology,Bonn, Federal Republic of Germany

X-irradiated wild type cells of Saccharomyces grow un-der appropriate conditions to a population of almostpure giant cells (budding but not dividing cei Is) whichexhibit one primary bud which in turn produces anothersecondary bud and so on. We investigated the morpholo-gical behaviour and the synthesis of macromolecules ofwild type strains and radiation sensitive mutants ofSaccharomyces carrying defects in the genes RAD 50 andRAD 52 respectively. Irradiation was performed at a \%survival level. Growth patterns, DNA-, RNA- and prote-in contents were measured. Morphology was documentedwith Calcofluor White, a fluorescent dye staining spe-cifically chitin rings. Results indicate that wildtype cells form giant cells with up to four bud equi-valents, wheras most rad 50 mutants display only doublecells. Rad 52 mutants remain single cells! 0nly about1% of the cells observed were able to divide. Macro-molecular synthesis continues in wild type strains,whereas in mutant strains DNA-and RNA contents increaseconsiderably, protein content, however, shows only aslight increase.

Wild type yeast cells capable of DNA repair synthesisare able to recover and to synthesize macromolecules,leading to the appearance of giant cells. Radiationsensitive yeast cells uncapable of DNA repair stop budformation although DNA synthesis itself seems to beunaffected. Although DNA is synthesized in mutant eel Iswe have to consider unrepaired DNA lesions to represscell growth as well as budding.

13

SIGNIFICANCE OP DIFFERENCES IN LATE PATHOLOGY OFIRRADIATED WISTAR RATSA. BAYEREeptTor Pathology, District Hospital , PreSovCSSR

The differences between autoptic findings inspontaneously decayed 147 non-irradiated and 356irradiated (X-rays, single whole body or partialexposure, 3 - 35 Qy) Wistar rats 300 - 1004 daysold, kept under identical conditions, were analysedstatistically. The incidence of malignant tumors inboth BBX9B and benign tumors in females was signi-ficantly (p<0,01) higher in the irradiated animals.However, among single tumors of organs only benignbreast tumors were significantly (p<0,05) morefrequent in irradiated females, and almost signi-ficantly - benign ovarian tumors. Among non-neoplas-tic diseases only polyarteritis nodosa exhibitssignificantly (pc0.05) higher incidence in irra-diated animals. On the contrary, some lesions weresignificantly (p<0,01) less frijuent in irradiatedanimals, as exulcerated bronchiectases, ulcers ofcoecum and cystic transformation of ileocoecallymph nodes* Significant differences were observedbetween males and females in the incidence of somediseases of neoplastic and non-neoplastic mature.

14STUDIES ON LONG TERM CONTINUOUS IRRADIATIONS ON THEB LYMPHOID SYSTEM OF Tl'E RAT.

HervS BAZIN1, Bernadette PLATTEAU1, Gisele PINON-LATAILLADE , & Jean MAAS .

Experimental Immunology Unit, Faculty of Medicine,University of Louvain, Brussels, Belgium andCommissariat a l'Energie Atomique, Departement deProtection Sanitaire, Centre d1Etudes Nucleaires deFontenay aux roses, France.

The effects of continuous exposure to caesiumgamma rays administered to rat at a daily dose of 0,0.07, 0.12, 0.20, 0.30 Gy for time up to 90 or 135days, have been observed on their B lymphocyte popu-lations and on their immunoglobulin serum levels.The effects increase with the daily dose and theduration of irradiations. At a daily dose of 0.07 Gyno clear effect was observed. At a daily dose of0.12 Gy, the depletion was almost negligible after30 days, and moderate for longer time, especially inthe case of the follicular B cells. At a daily doseof 0.20 or 0.30 Gy, both the follicular and themarginal zone B compartments were depleted. Howeverthe marginal zone B population was much more affectedthan the follicular one. IgM and IgG serum levelswere decreased by chronic exposure to irradiation atdose equal or superior to 0.20 Gy per day. IgA serumlevels were increased by the same doses. A cleardifference in susceptibility was observed between themarginal zone B compartment and the follicular one,the former being much more affected by the ionizingradiations than the second.H.B. staff member of the Commission of the EuropeanCommunauties (publication nr 2224) - supported inpart by grant BIO 512 B from Euratom.

15

RBEn>nOF NEUTRON BEAMS PRODUCED BY 34, 45, 65 AND 75 MeVPROTONS AND BY 50 MeV DEUTERONS FOR INTESTINAL CRYPTS REGE-NERATION.

M. BEAUDUIN, J. GUEULETTE, B.M. DE COSTER, S. VYNCKIER andA. WAMBERSIE.

Cliniques Universitaires St-LUC, UCL, 1200 Bruxelles (Belgium)

As different neutron beams are used in clinical neutronthe-rapy, it is necessary to compare their radiobiological proper-ties in order to interpret the clinical results* For thispurpose, we determined the RBE of neutron .beams produced, atthe variable energy cyclotron "CYCLONE" of Louvain-la-Neuve,by bombarding a beryllium target with 33, 45, 65 and 75 MeVprotons and with 50 MeV deuterons. The biological criterionis the regeneration of the intestinal crypts after total bodyirradiation in mice (WITHERS technique). Tihe reliability ofthis criterion with respect'to the LD50 for evaluating earlyintestinal tolerance in our experimental conditions was chec-ked by comparing the RBE values yielded by each criterion.The p(65)+Be neutron beam RBE (ref. 60-Cobalt gamma-rays) wasfound equal to 1.60+0.20 and 1.75+0.25 for the regenerationof 50 intestinal crypts at the 3.5rd day and for the LD50at the 5th day respectively (the irradiations were performedin 1 fraction). Although this difference is mot significant,it could be explained by the difference in the correspondinggamma dose for both criteria (12.3 Gy for regenerated cryptsnumeration and 11.5 Gy for LD50).

The variation of neutron RBE as a function of energy forintestinal crypts regeneration shows an increase of the RBEwhen the neutron energy decreases. Nevertheless, this in-crease is smaller than the 20% increase observed in Viciafaba, for an enetrgy variation from 34 to 75 MeV protons onberyl Mum.

1 6

CONTINUED RESEARCH ON THE DEVELOPMENT OF CORK ANDVEGETABLES AFTER PREVIOUS GROWTH IRRADIATION EMIT-TED BY SHORT WAVE DIATHERMYE . BEDASanatoria* in Ssczawnica, PolandAfter having proved the beneficial reaction of

short wave diathermy (SWD) on the growth of 4 kindsof corn, the size of their ears of corn, grain andtheir number (7th Intern, Congress of Radiation Re-search-E8-02) also after continuing similar influen-ce on the 2nd crop without the use of SWD (R£vue Ei-ne*sither. Re~adaptation 1983, 2, 5, 10-Belgique).I decided to continue and expand my previous expe-riments. With this aim I have observed:1* The growth of the 3rd wheat crop, rye, barley

and oats without the use of SWD.2. After exposing them to SVS aa in my first #work,

the grain of the winter corn rape-seed (Oorcsane-ki type) and their growth after planting*

3* Expanding identical procedinge (SWD) comparingwith the controlled group of vegetables chosen:lettuce, parsley, celery, dill, radisches.

Results were very similar to the previous ones*Conclusions reached: Further expansion of experi-ments which may prove that SWD on the growth ofmany plants may benefieialy influence their growthand transmit their hereditary properties.Very similar influence of SWD on a few kinds of

grain and vegetables may prove wider possibilitiesof the aforementioned method*

17

A NEW FACILITY FOR RADIOBIOLOGICAL STUDIES WITH PROTONBEAMS: SURVIVAL AND DNA DAMAGE IN V-79,£ELLS.M.Belli^, S.Mazzucato'1 ,riM.Morando

U , G.MoschiniO.Sapora( J, M.A.TabocchiniU;7(l)Istituto Superiore Sanita and INFN-Sanita, Roma.(2)Laboratori Nazionali di Legnaro dell'INFN, Padova.

A beam line dedicated to radiobiological studies hasbeen set up at the Laboratori Nazionali di Legnaro,Padova (Istituto Nazionale di Fisica Nucleare). The lineis connected to a CN-7 MV accelerator and is particularlysuitable to study the radiobiological efficiency ofproton and alpha particle beams near the Bragg peak. Thefacility makes it possible irradiation under atmosphericpressure of cultured cells with monoenergetic particlebeams in the energy range 0-6 MeV at dose rates from tensof mGy/min to tens of Gy/min. The beam Ainiformity isbetter than 5% on a cross-section of 110 mm .

Survival curve of V79 cells irradiated with 4.7 MeVprotons has been compared with that obtained with 200 kVX-rays. No initial shoulder has been found with protons,and their RBE at 10% survival was about 3.

The number of DNA double strand breaks has been alsomeasured. Linear dose-effect relationships have beenfound for both protons and X-rays. The RBE for thiseffect has been evaluated to be about 5.

These results suggest that a direct relationshipcannot be drawn between initial molecular lesions (i.e.,DNA dsb) and damage at cellular level (i.e., reproductivedeath).

18

DISTRIBUTION OF RADIATION DAMAGE OF DNA IN CELLPOPULATION AND IN SINGLE CELLS AFTER HOMOGENEOUSIRRADIATION WITH FAST NEUTRONSL. BENEg, E. ROTREKLOVA

Institute of Biophysics, Czechoslovak Acadeny ofSciences. Brno, CSSR

Detection and repair of errors in the DNA Mole-cule are indispensable processes for the preserva-tion of the DNA informational integrity. Underphysiological conditions the probability of occur-rence of errors in DNA depends on accidental tau-toneric changes of the bases and on a Halted spec-ificity of enzymes involvsd in DNA synthesis. How-ever, in relation to the concentration of tautomericprecursors in the pool, the actual level of errorsin DNA is lower due to "proof-reading" or "peel-back" mechanisms. The probability of the insertionof a correct dNTP or of the removal of an incorrectone can be expressed by means of Poisson distribu-tion. In cells exposed to 6.2 MeV neutrons theprobability of errors in the DNA molecule increased.The homogeneity of the radiation field guaranteedthe same probability of DNA damage for all thecells. DNA damage was indicated occording to theinduction of unscheduled DNA synthesis (UOS), whichis a step of DNA repair processes, in single cells.Ths number of cells with UDS was limited and grewwith the dose. The grain distribution in the auto-radiographs of cells with UDS followed Poisson'scurve. If, e.g., 2 grains represented a repairlocus, then after homogeneous irradiation therewere cells found with no DNA damage and those withDNA damaged in 1 to 12 loci. Also the frequency ofchromosomal aberrations showed Poisson distribution.

19

COMPARATIVE STUDIES ON RADIOPROTECTIVE AND ANTI-MUTAGENIC PROPERTIES OP A RADIOPROTECTIVE MIX-TURE, ATP-AET-SEROTONIN, AND THE PREPARATIONWR 2721D. BENOVA. G. KIRADZHIEV, M. NIEOLOVA

Institute of Roentgenology and Radiobiology,Sofia, Bulgaria

Two radioprotective agents, a mixture of ATP-AET-serotonin in doses of 360, 24, and 8 mg/kgb.wt., respectively, and the preparation WR 2721at 400 mg/kg, were studied for radioprotectivepotency in C57B1 mouse males.Based on radiation deaths, the dose reduction

factors (DRP) amounted to 1.6 for the mixture and1.7 for WR 2721.In terms of reciprocal translocations induced

in spermatogonia by 4.0-Gy X-rays, the reductionfactors (RF) obtained were 1.8 and 2.4 for themixture and WR 2721, respectively.

20

TESTING WR 2721 AND ATP FOR ANTIMUTAGENIC POTEN-CY AGAINST RADIATION-INDUCED SOMATIC-CELL CHROMO-SOME ABERRATIONS IN THE MOUSED. EENOVA. I. RUPOVA

Institute of Roentgenology and Radiobiology,Sofia, Bulgaria

The preparations WR 2721 (S-2-/3-aminopropyl-amino/ethylphosphorothioic acid) and ATP (adeno-sine-5-triphosphoric acid disodium salt) weretested for radioprotective effectiveness againstinduction of chromosome aberrations after 3»0-Gygamma irradiation of mouse bone marrow cells.When administered 20 min prior to radiation ex-posure, 400 mg/kg b.wt. WR 2721 was observed toappreciably reduce aberration frequency. Pre-treatment with 360 mg/kg ATP resulted in a slightprotective trend, the effect being statisticallyinsignificant.

21

STIMULATION OP LYMPHOCYTES BY SPECIFIC BACTERIALANTIGENS AFTER NEUTRON IRRADIATIONM.Beno, D.Piknova, A.Hrabovcova, f.Batorova

Research Institute of Preventive Medicine,Brati slave,5SSR

Samples of whole blood taken from healthy hunandonors were irradiated in vitro by various dosesof a 252-caIifornium source neutrons .After irradi-ation the mononuclear cells have been isolatedand suspended into RPMI 1640 medium containingbacterial antigens prepared from B. pertussis andE.coli. The intensity of stimulation of the lympho-cytes in the mononuclear isolates was assessedusing tritiated thymidine incorporation at variousintervals up to eight days after irradiation.The results showed significant suppression of thetritiated thymidine incorporation into stimulatedcells after irradiation of blood samples withdoses higher than 0,4 Gy. The suppression persis-ted from the fourth to the eighth day afterirradiation and setting-up the cultures.Various aspects of the RBE of neutrons using thelymphocyte in vitro stimulation as a modelassessment system are discussed.

22

EFFECTS OF SULPHYDRYL AGENTS ON THE RADIATION-INDUCEDDECOMPOSITION OF NUCLEIC ACIDS AND RELATED NUCLEOSIDES

M. BERGER , J. LAVAL AND J. CADET1 Laboratoires de Chimie, DRF, Centre d'Etudes Nucle"aires de

Grenoble, 85 X, F-38041 GRENOBLE CEDEX, France2 Institut de Recherche sur le Cander G. Roussy, CNRS,

F-94805 VILLEJUIF CEDEX, France.

Various sulphydryl agents including cysteine and gluta-thione have been found to protect living cells against thelethal effects of ionizing radiations. One possible mode ofaction of these radioprotectors is the chemical repair ofradiation-induced radicals within biomolecules such as nucleicacids. Attempts have been made in this study to determine howthe above sulphydryl agents may effect the radical eventsinduced in DNA and related 2'-deoxyribonucleosides uponexposure to gamma rays in oxygen free aqueous solutions. Thegamma irradiation of 1 mM thymidine in deaerated aqueoussolutions containing 0.5 mM cysteine or glutathione led to asignificant reduction in the number of decomposition productsbut with an increase in the overall degradation. This sensitiz-ation effect which concerns mostly the thymine moiety may beaccounted for by efficient hydrogen or electron transfer tothe radiation-induced pyrimidine radicals, preventing resti-tution reactions which are of importance in the absence ofsulphydryl agents. On the other hand, the presence of the RSHcompounds in the irradiated solutions of 2'-deoxyadenosine or2'-deoxyguanosine prevents any significant degradation of thepurine bases. Notable protective effects are also noted forthe sugar moiety of all the purine and pyrimidine nucleosides.Only the q-D-erythro and n-L-threo isomers of thymidine and2•-deoxyguanosine which may be explained by epimerizationreactions of carbon centered radicals at positions 1* and 4*respectively are formed in detectable amounts. Related re-actions have been shown to occur in DNA and polynucleotideswhich are used as substrates in the search for N-glycosylaseactivity against 5,6-dihydrothymine derivatives.

233FFJ3CT 0 ? IRRADIATION OH S3RUE T, LEVEL AND rOF THYRDIIO GLAND TO EXOGENOUS TSH IN RATS

L.BERgOK. S .U. NAGY

"Frederic Joliot-Curie" National Research Institutefor Radiobiology and Radiohygiene andDepartment of Biology, Semmelweis Medical UniversityBudapest, Hungary

In earlier experiments it was demonstrated that thethyroid function of rats decreased in various forms/eg. endotoxin, intestinal ischemia induced bysuperior mesenteric artery occlusion, tourniquet/ ofexperimental shocks /U.Nagy, Csaba and Bertok, 1983,U.Nagy and Bertok, 1984/. In present experiments asignificant decrease of the serum T. /thyroxine/level and T. response of thyroid glSnd to exogenousTSH of X-ray /8 Gy whole-body/ irradiated rats wasproven on the day 7 after irradiation. However, thelocal irradiation of thyroid gland did not cause asignificant change in the function of thyroid gland.Authors suppose that enteroendotoxemia developingduring intestinal syndrome of radiation disease/Bertok and Kocsar, 1974; Heming and Northdurft,1977/ is one of the reasons of the lowering of thefunction of the thyroid gland.

24SURVIVAL OF HUMAN MELANOMA CELLS AFTER X-RAYS, HYPERTHERMIAAND NEUTRON THERAPY

D. VAN BEUNINGEN, C. StrefferInstitut fur Med. Strahlenphysik und Strahlenbiologie,Universitatsklinikum Essen, D-4300 Essen 1, F.R.G.

Two human melanoma cell lines (Bell; MeWo) were studiedduring exponential growth and during plateau phase. The sur-vival was measured after hyperthermia treatment (3 h, 42°C),after X-irradiation, after the combination of X-rays and heatand after neutron irradiation. TER- and RBE-values are calcu-lated. During the exponential growth the heat sensitivity ofboth cell lines was similar, the radiosensitivity was different(MeWo: Dq 1.6 Gy, D o 1.0 Gy, Be11: Dq 2.6 Gy, Do 1.2 Gy). Afterthe combined treatment the shoulders of the dose effect curvesdisappeared completely in both cell lines. Also after neutronirradiation the same effect was observed. The TER- and RBE-values decreased from 4 to 2 with increasing radiation doses(dose range 0.5 to 4.0 Gy). In the plateau phase the radio-sensitivity of the melanoma cells decreased (Bell: Dq 1.9 Gy,MeWo DQ 0 Gy). In the Be11 the thermosensitivity decreased,in the MeWo-cells it increased slightly. After the combinedheat and X-ray treatment in the MeWo-cells no radiosensiti-zation of the plateau phase cells was observed by the heattreatment, in the Bell-cells the shoulder was reduced (TERvalues decreased from 3.5 to 1.7). The effects could not beexplained by the different cell proliferation during exponen-tial and plateau phase growth, which was measured by flow cyto-metry.

25RADIATION EFFECT ON CNS IN NMR IMAGEC.BIAGINI,F.CAMPODONICO,S.GIANNINI,F.VITELLIRadioth.Dept.,Inst.Radiol.Univ.Rome,INI,Grottaferrata,Rome

From June to November 1984, 67 patients with tumors in-volving CNS underwent NMR Imaging at the INI Center. Imageswere acquired with a 0.15 T resistive system, using a multi-pi e-SE pulse sequence, TE 50-200 msec, TR 500-2000 msec. 15out 67 patients were subjected to NMR examination for que-stionable evidence of tumor recurrence. Assumed signs of ra-diation effect were the following: cerebral edema, expres-sed by elongated 1- and T«; transient enlargement of the ven-tricular system; peri ventricular edema; areas of demyelina-tion associated with persistent lenghtening of T. and T2;necrotic leukoencephalopathy, represented by extremely longT1 and T~ values or more complex modifications of NMR para-meters. In 10/15 patients some abnormalities were evident.In 4 cases the outline of the lesion was consistent with iso-dose curves, suggesting the evidence of radiation damage.In 6 cases it was difficult to make a distinction betweenafter effects of surgical intervention, radiation injury,drug toxicity, and persistence of disease or recurrence.

26

THE EFFECT OF RADIOFROTECTORS AND IRRADIATION OKTHE PLATELET KONOAMINE OXIDASE ACTIVITY

K. BODO, GY* BEHKO

"F.J.C." Natl. Res. Inst. for Radiobiol. Radiohyg.Budapest, IiUN.

Monoamine oxidase (MAO) activity in blood plate-lets has been assumed to mirror the activity ofthis enzyme in the brain, and the activities ofboth are related to central monoaminergic activity.Authors examined the activity of rabbit platelet

MAO after the incubation with various radioprotec-tors in vitro. Platelet MAO activity was measuredby spectrofluorimetric method using kgnuramine assubstrate. It was stated that 2,5x10"° M/ml AETdoes not cause any change but 1x10~? M/ml AET resul-ted complete enzyme inhibition. At the same timeWR 2721 in 6x10"° M/ml and 2X1O"-3 M/ml concentrati-on range has not effected platelet MAO activity.After 1 hr of in vitro 10 Gy gamma-irradiation en-zyme activity decreased by 25 #>•After in vitro experiments authors determined thein vivo effect of AET and WR 2721 on platelet MAOactivity of rabbits. It was found that pretreatmentwith AET reduced the enzyme activity while WR 2721had not such effect. The platelet MAO activity wasstudied after lethal dose whole-body gamma-irradi-ation. In this experiments enzyme activity changedin the same direction an it was found in the invitro experiments.

27

,ACTIVITY OF PURINE NUCLEOSIOE PHOSPHORYUSE IN

-RACTIONATED ERYTHROCYTES OF RATS AFTER GAMMA IRRA-

DIATION

J. Bohacek. B. HoSek, 0. Kauteka, D, Sikulova

Institute of Biophysics, Czech. Acad. Sci., Brno,

Czechoslovakia

Purine metabolizing enzymes are being encounte-

red in an increasing number of disorders including

radiation damage* Activity of purine nucleoside

phosphorylase (PNP) in fractionated erythrocyte

samples was studied after sublethal irradiation of

rats. Blood samples (2O,ul) were taken from the

caudal vein 48 hours before and 48 hours after the

whole-body gamma irradiation (dose 3 Gy, dose rate

0.4 Gy.min" ). The erythrocytes were fractionated

according to density using centrifugation in micro-

hematocrit capillaries. Three fractions were ob-

tained by cutting the capillary. High performance

liquid chromatography (HPLC) was used for the PNP

activity estimation. After irradiation of rate the

gradated decline of tho PNP activity was found in

the measuretd fractions. The greatest decrease (52 %

of the initial activity value) was observed in the

specifically lighter top fraction of erythrocytes

corresponding to the younger forms of red blood

cells.

28

THE EFFECT OF COMBINED TREATMENT WITH PLATINUMCOMPLEXES AND RADIATION ON DNA IN VITRO

V. Brabec and 0. Vrana

Institute of Biophysics, Czechoslovak Academy ofSciences, Brno, CSSR

The effect of cis-diamminedichJLoroplatinum(II)(cia-DDP) and its trans-ieomer (trans-DOP) in com-bination with gamma irradiation on the structureof calf-thymus DNA was studied by means of diffe-rential pulse polarography and the measurement ofcircular dichroism spectra* It was found that re-latively low doses of radiation and the binding ofantltuMour active cis-DDP induced only small"preaelting" alterations in DNA conformation. Onthe other hand antitumour inactive trans-DDP indu-ced more drastic changes in DNA structure leadingto denaturation of this biomacromolecule. Thecombined affect of these platinum compounds andradiation caused a marked Increase in the extentof the conformational changes caused by the singleagents. This increase was dependent on the orderof application of the platinum compound and radia-tion. It was concluded that increased antitumouraction of combined effect of cis-DDP and radiationcould also originate in the higher content of"preaelted" regions in DNA induced by the twoagents.

29 '•:

PRACTICAL ASPECTS OF DOSIMETRY FOR RADIOBIOLOGYJ.J. Broerse and J. Zoetelief

Radiobiological Institute TNO,P.O. Box 5815, 2280 HV Rijswijk, The Netherlands

The physical conditions of an irradiation including theamount of energy deposited in the course of time and thegeometrical arrangements determine the degree of biologicaldamage induced. Differences of 10 per cent in absorbed dose canproduce an all-or-nothing detrimental effect in animals andmen. The assessment of LD,_ values in terms of mid-lineabsorbed dose in various species will depend to a large extendon the degree of inhomogeneity of the dose distribution.Phantoms are often used to determine the absorbed dosedistribution in a biological specimen. It can be concluded thatfor whole body irradiations acrylic plastic is a reasonablesubstitute for animals of the dimensions of a mouse and thatpolyvinylchloride can not be recommended as phantom material.

The X-irradiation procedures at a number of Europeanlaboratories will be summarized. For partial body irradiationof specific organs such as lung and liver in the rat bilateralexposures are necessary to fulfil the recommendations forhomogeneous irradiation. These irradiations should be performedwithout back scatter material to limit the doses in theshielded parts of the animal. The presence of low density lungmaterial introduces considerable differences in attenuation andscattering in comparison to the situation in a homogeneousphantom. For small phantoms the processes of attenuation andscattering compensate each other. However, for larger phantomsthe attenuation process predominates and the relative dose inthe lung is increased considerably. The introduction of acommon dosimetry protocol has resulted in appreciableimprovements in exposure arrangements and absolute dosimetry atinstitutes cooperating within the European Late Effects ProjectGroup (EULEP).

30

EFFECT OF 5-FLU0R0DE0XYURIDINE ON ONA REPLICATIONAND SURVIVAL IN ULTRAVIOLET-IRRADIATED HeLa CELLS

3. Brozmanova and B. I. Synzynys

Cancer Research Institute, Slovak Academy of Scien-ces, Bratislava, CSSR and Research Institute of Me-dical Radiology, Academy of Medical Sciences, Ob-ninsk, USSR

It is well-established, that certain precondi-tioning DNA inhibiting treatments enhance cellularresponse to damage in ONA. We found previously thatthymine prestarvation led to the increase of repairactivity in E. coli cells damaged by ultraviolet(u.v.) light. To detect the similar phenomenon ineukaryotic cells, the influence of a prior periodof cultivation with fluorodeoxyuridine (FdUrd) onthe resistance to u.v* and the restoration of ONAsynthesis in HeLa cells damaged by u.v. light hasbeen studied. Cultivation for 6 hours with FdUrdand 18 hours in FdUrd-free medium slightly increa-sed the fraction of surviving cells and markedlystimulated post-irradiation DNA synthesis in u.v.--irradiated HeLa cells. DNA synthesized in FdUrdpretreated and u.v.-irradiated cells showed morerapid shift of the pulse-labelled-chased DNA tohigh molecular weight. As the ueed FdUrd treatmentinhibited DNA synthesis without an apparent Influ-ence on both the plating efficiency and the degreeof synchrony, we favour the hypothesis that theenhancement of DNA recovery represents a cellularresponse to inhibition of DNA synthesis by F.dUrd.

31

OPTICAL MULTICHANNEL ANALYZER FOR THE DETECTION OFTHE LIGHT-EMISSION SPECTRA OF THERMOLaMINESCENCEMATERIALP.BRUNNER, G.BAKAS, O.BOBLETER, W.AMBACH

Thermoluminescence-materials are widely used inthe field of medical and biological dosimetry. A newoptical multichannel analyzer was developed for themeasurement of the spectral distribution of thewave-length of TL-light emission. The equipmentallows the simultaneous detection of 256 channelsof a charge-coupled device (CCD), on which the bya prisma dispersed light of thermoluminescence mate-rials was focussed. 3D-plots show the intensity ofthe emitted light as a function of the wave-lengthand the heating temperature of the material. In thatway not only the emission light spectra, but alsothe applied dose on CaF2:Dy,TM and CaSO4:Dy,Mn canbe calculated. It is shown that a well known opticalspectrum of the light emission of TLD allows theoptimization of the photomultipliers used and themodification of the pre-heating cycle of the TL-material.

32COMPUTER CONTROLLED GROWTH CHAMBER FOR THE PRODUC-TION OF C-14 LABELLED PLANTSP. BRUNNER. A. GOTWALD, O. BONN, W. AMBACH, 0. BOB-LETER

C-14 labelled plants are often used in the ana-lytical chemistry connected with biological prob-lems. A growth-chamber allows the production ofplants in a C-14 labelled environment. 10/% of thenaturally occurring C02 are replaced by *C02. Thecontent of C02 and the C-14 labelled C02 are compu-ter-controlleft by means of a infrared absorptiondetector and a flow-type proportional counter, res-pectively. The obtained data are chained to a CB1I8062 via analog-.digital conversion.

The C02 and C02 concentration are measuredand controlled simultaneously. Furthermore the tem-perature and the humidity as well as the light areautomatically held at preselectable values. Thevalibratioa of the whole system and the radioacti-vity in the platns is shown* Various uses of theradiocarbon labelled plants are demonstrated.

33

ALLOSENSITIZATIQN IN TUMOR THERAPY AND PROPHYLAXISAND IN FEMALE CONTRACEPTION - A PROSPECT FOR CLINI-CAL USEA. BUKOVSfCY and J. PrealInstitute for the Care of Mother and Child, Prague.fiSSR

A hypothesis ia presented on the possible roleof allosensitization in therapy and prophylaxis ofhuman tumors, and in human female contraception*The essence of proposed treatment of human malig-nancies is allosensitization with allogeneic whiteblood cells by means of application of two bloodtransfusions from healthy donors within a certaintime interval to patients with invasive or metaata-sizing cancer. The therapy should be accompanied bybacterial toxins and a single dose of cytostatics.It is suggested that tumor rejection can be media-ted not only by the direct effect of anti-tumordrugs but more effectively by the organisms mecha-nisms responsible for removal of undesirable tissuei.e. mediated through the immune system* Patientswho hare undergone prolonged and/or high dose cyto-static therapy, high dose irradiation, excessivesurgery, and exhausted cases close to death arelikely to be low responders to the proposed treat-ment. In the case of successful tumor regression aprophylaxis of recurrence should be made with twodoses of intradermally injected allogeneic lympho--leukocytic concentrates mixed with bacterial to-xins; such treatment might also be effective intumor prophylaxis, or in long-lasting contracepti-on in women. The therapeutic, prophylactic andcontraceptive schedules suggested represent aninexpensive type of treatment which, if of practi-cal use, should be promoted.

34

CYTOGENETIC EFFECT FOLLOWING EXPOSURE OF HUMANLYMPHOCYTES TO HELIUM NUCLEIM. BULANOVA. M. MILEVA, I. GEORGIEVA, B. IVANOVInstitute of Roentgenology and Radiobiology,Sofia,Bulgaria

The purpose of the investigation was to ascer-tain frequencies of chromosomal abnormalities pro-duced by 'in vitro1 exposure of human peripherallymphocytes to a range of doses of helium nucleidiffering in energy,and to compare the results withthose from exposure to 60co gamma rays given at adose rate of 0.53 Gy/min.Irradiations of the blood with helium nuclei:

energy 4.6 GeV/nucleon,dose rate 0.015-0.02 Gy/sec,intensity 5 x 1O9 particles/pulse,and doses of0.20, 0.58, 0.96, 2.05, 3.91 Gy; and energy 4.0GeV/nucleon,dose rate 0.01 Gy/sec,and doses of 0.5»1.0,2.0, 4.0 Gy.Irradiated cells were cultured for 51hours.The genetic structures in human somatic cells

proved highly sensitive to irradiation with heliumnuclei.Aberrations were predominantly of chromoso-me type.For the two energies used,dose-responserelationships were found to be similar in nature:linear for aberrant cells,and linear-quadratic fordicentrics,rings,and total amounts of aberrations.Based on regression coefficients for doses produ-

cing equivalent effects,REE values were derived for4.6 GeV/nucleon helium nuclei relative to 60Co gam-ma rays.Some endpoints yielded RBEs close to unity.With regard to distribution of aberrations percell,helium nuclei were found to be more effective.

35

AN ESTIMATE OF THE LUNG CANCER RISK FROM RADON AND ITS DECAYPRODUCTS IN ALPINE DWELLINGSW. BUR'KART

Biology & Environment, Abt. 81, EIRCH-5303 Wiirenlingen / Switzerland

In large areas of the Swiss Alps, the high radium contentof rocks and soil, which results in high source terms forradon from the ground, may produce considerable indoor levelsof radcin in dwellings with low air exchange rates. A sampleof 32 conventional homes in Southeastern Switzerland, an areawith generally high uranium concentrations in the subsoil,showed an arithmetic mean radon concentration in livingquarters and cellars of 307 Bq/m3'' (8.3 pCi/1) and 1410 Bq/m3(38.1 pCi/1), respectively. Energy conservation efforts suchas weatherstripping were shown to increase radon levels anddoses further.

Using UNSCEAR82 conversion factors, the annual effectivedose equivalent in this area amounts; to 9 mSv (900 mrem). Thecorresponding dose to the stem cells of the tracheobronchialtissue is about 100 mSv/a (10 rem/ea). Life time exposure insuch dwellings is in the range of occupational dosescollected in modern uranium mines and leading to asignificant increase in the lung canosr risk. The use of riskfactors derived froia epidemiological evidence on minerpopulations: exposed to generally high levels of radon decayproducts leads to the prediction of considerable risks fromradon in r.he indoor environment. In geological areas withhigh radon source terms, remedial action should beimplemented.

36

OFFSPRING'S RAOIORESISTANCE INCREASED BY MATERNAL

STIMULATION

S. CABA0A3, 3, FILOVA. M. PRASLlCKA

Institute of General Biology, P.O.Safarik Univer-

sity, Koiice, CSSR

Pregnant female rate were injected intraperi-

toneally with befcnzene extracts of human blood

cell* dissolved in ethanol, on day 13, 17 and 21

of pregnancy. The 14 week old offspring wae irra-

diated 49 hours by gamma rays, till the total do-

se of 15,6 Gy. The oortality rate was afterwards

followed during 30 days. The control groups were

injected either by pure solvent /Cj/or not trea-

ted at all /Cg/.

Survival rate in offspring of mothers treated

with the blood cell extracts was on the average

43 per cent higher than in controls.No signifi-

cant difference in survival rate between the groups

C^ and C 2 v«a8 found.

The extracts injected to mature male rate in-

creased their resistance to ionizing radiation.

Complement-fixing antibodies against those ex-

tracts are present in normal human sera with occu-

rence depending on age and sex /Cabadaj at al*,

1980, Cas. L«k. Cos. 119. 1207, in Slovak /.

37

RECONSTITUTION OF THE LYMPH NODES OF DOGS AFTERFRACTIONATED TOTAL BODY IRRADIATION AND TRANSFUSIONOF FETAL LIVER CELLS

W. CALVO, O. PRUMMER, F. CARBONELL and T.M. FLIEDNER

Department of Clinical Physiology and OccupationalMedicine, University of Ulm, D-79OO Ulm, FRG

Eleven beagles were total body X-irradiated with 3fractions of 6 Gy each (0.07 Gy/min) at 48-hourintervals and were transfused with suspensions offetal liver cells from DLA-identical or haplo-identi-cal siblings, containing 9 to 93 thousand CFU-GM perkg body weight. Bone marrow regeneration occurredrapidly in all animals, while the thymic remnantswere fatty and hypoplastic. Lymph nodes were studiedat autopsy between days 57.and 163 after transplant-ation. All lymph nodes showed a normal structurewith numerous lymphocytes and germinal centers. Moder-ate to abundant plasma cell numbers were found in theparacortex and medullary areas. Small to moderatenumbers of phagocytes were also present. Granulo-poiesis was noted in 7 cases and megakaryocytes werepresent in 2 cases. The number of lymphocytes inblood was very low during the week after irradiation,started to increase the weeks thereafter and reachedpre-treatment values between days 75 and 101. De-creasing numbers of host lymphocytes were found inthe blood and at the end of the observation period,all metaphases were of donor type. Canine fetal livercells are able to rescue lethally irradiated recip-ients and to restore lymph node morphology.

(Supported by the Radiation Protection Programme ofthe Commission of the European Communities,BIO-C 345-8O-D no. 2185)

38

THE EFFECT OF ARTIFICIALLY INDUCED HYPERGLYCAEMIA ON THERADIATION RESPONSE OF THE LEWIS LUNG CARCINCT1ADAVID J. CHAPLINMedical Biophysics Unit, B.C. Cancer Research Centre,Vancouver, B.C. V5Z 1L3 Canada

In the treatment of any malignancy it is essential toutilize all known physiological differences that exist betweentumour and normal tissue. One well established difference isthat tumours in both rodents and man have a lower pH thannormal tissue. Further reduction in tumour pH is thought tooccur in necrotic regions remote from the blood supply. It isnow widely believed that cells close to.these necrotic regionsare protected from the effects of radiation by their hypoxiathus providing the foci for tumour regrowth followingtreatment. Yet, since these cells are*situated in regions ofacidic pH it might be expected that further pH drops willdecrease their viability. Hyperglycaemia is known to increasetumour acidosis and its effect on the radiation response ofthe Lewis lung carcinoma is being evaluated. Our resultsindicate that hyperglycaemia (induced by IP injection ofglucose Bmg/g) can increase the radiation response of theLewis lung carcinoma. The extent of the effect beingdependent on the time between glucose injection andirradiation. Further in vivo studies are now planned toassess the clinical potential of such treatment. (This workis supported by a grant from the National Cancer Institute ofCanada).

39

PRIMARY ACUTE EFFECTS IN THE CORTEX AND LIMBICSYSTEM OP THE BRAIif INDUCED BY LASER IRRADIATIONOF THE BRAIN OF THE RAT

S.A«Chepurnoy, N.E.Chepur*•«*.a, U.V.LikhachevMoscow Lomonosov State University, Moscow, USSR

Electrical activity changes in the reticularformation, hypothalamus, amygdala and neocortex we-re studied after single pulsed laser irradiation(IO~3, I0~8 s) of the head of the rat using high in-tensive ruby and neodymiuin lasers. During experi-ments all subjects were anesthetized with sodiumpentobarbital. These changes were the result ofbrain trauma and ultrastruetural alterations in thebrain glia and neurons and correlated well with thedevelopment ^f vascular damage. The laser pulsedirradiation of the cerebellum served as the secondcontrol test, as a result of wich reversible motorcerebellar disturbances developed. Control measure-ments by I.B.Laprun ir -iod (1981) demonstrated thatthe amount of energy »;. ich penetrates through theskin, bones and layers of the cortex tissue is lessthan 10$ and is comparable to low intensity laserirradiation of the brain. This was in confirmitywith the well known high reactivity of limbic struc-tures during X-ray radiation. Our elektron microsc6-pic investigations of the cortex during the acuteperiod indicated changes in the capillaries,an inc-rease in the length of the cariolemma, a bending ofthe nucleus membrane of glia and neurons of the cor-tex; a desorganisation and concentration of the chro-matine globus, an increase in the number of riboso-mes, polisomes and cistern of granular reticulum.There were no changes the vesicules in the presynap-tic terminals.

40

LATE PATHOMORPHOLOGIC CHANGES IN THE TESTES OF MICEAFTER X-IRRADIATION WITH SUBLETHAL DOSES AT DIFFE-RENT AGES

K. CHOMICZEWSKI , A.K. GAJEWSKI

Department of Pathomorphology WAM, L6dz, and StateInstitute of Hygiene, Warsaw, Poland.

The effect of age on the development of late post-

radiation pathomorphologic changes in the testes has

been investigated in an inbred A strain of mice. The

animals were exposed to a single, whole-body dose of

7.74* 10"*2 Okg**1 /300 R/ of X-rays at the age of 1

day,1,2,3,4,5t6,7,10 weeks, 6,12 and 13 months of li-

fe. The testes were evaluated by routine and quanti-

tative microscopy at 6 and 18 weeks after the irra-

diation and at 24 months of life* The results indica-

ted impairment of speranato- and spermiogenesis in all

irradiated groups after 6 weeks of observation. In

the later periods of examination the postradiation

injury diminished, but except one group irradiated

at the age of 4 weeks, significant differed with the

controls. The most severe lesions in all periods of

examination were observed after irradiation of new-

borns.- The results indicated the dependence between

the degree of the postradiation damage, the ability

of the seminiferous epithelium to the regeneration

and the age of irradiation.

41EFFECT OF IN VITRO EXPOSURE TO X RAYS AND HYPOTHER-MIA ON OF HAMSTER MELANOMA CELLSK« CIESZKA. R. GURBIEL. M. KAPISZEWSKA. Kf HYRCInstitute of Molecular Biology, JagiellonianUniversity, Cracov, Polsnd

Our earlier experiments indicate that the highradioresistance of melanotic cells can be relatednot only to the direct interaction of radiolyticalfree radicals with melanin, butalso to indirectreaction of both free radicals and melanin with oxy-gen. Intercellular O2 concentration can be modifiedby the rate of O? consumption and 0? concentrationin the environment. Both the factors depend on tem-perature. Therefore, irradiation of melanoma cellsat low temperature seemed to be a simple way to in-crease cell radiosensitivity* The aim of the prese-nt work was to test this assumption by determiningthe value of oxygen enhancement ratio (OER) a*t 0 Cand 20 C. Pigmented Bomirski hamster melanoma cellsderived from cell cultures were irradiated with dif-ferent doses of X rays at 0 C and 20 C under normaland hypoxic conditions. Immediately after irradia-tion cells were injected intracutaneously into gol-den hamsters. Finally, the number of irradiatedcells which were able to divide was calculated.Survival data (0°C: D =2.0 Gyj 20°C: D=4.8 Gy)show that cells irradiated at low temperature aremore sensitive to radiation than cells irradiatedat the room temperature* This result may be relatedto high oxygen concentration in cells at the lowtemperature, such explanation being supported bythe relatively high radioresistance of melanomacells irradiated at 20 C under hypoxic conditions(0*8.5 Gy). Therefore the high radioresistance ofmelanoma cells may be related to interaction of me-lanin, oxygen and radiation*

42COMPARISON OF THE LETHAL EFFECTS OF X IRRADIATIONAT C^C IN MELANOMA AND CHO CELLS IN VITROK. CIESZKA. M. KAPISZEWSKA. R. GURBIEL. K. HYRCInstitute of Molecular Biology, Jagiellonien Univer-sity, Cracov, Poland

In vivo studies have shown that Bomirski hamstermelanoma cells irradiated with X rays at 0 C invitro are more radiosensitive "than cells irradiatedat the room temperature. The aim of the presentwork was to investigate the mechanism of the highradiosensitivity of cells irradiated at the low tem-perature* CHO and B16 melanoma cell cultures werecooled to 0 C, maintained for 20 minutes at thistemperature and irradiated with different doses ofX rays. Cell cultures were cooled at various ratesto check the role of thermal shock in cell killing.CHO cells are more radiouensitive than B16 melanomacells.irrespectively of the temperature at whichirradiation was carried out* In CHO cells the effectof X irradiation does not dependent on the tempera-ture during experiment (D = 1.1 Qy both at 0 and20 C ) . In contrast, B16 melanoma cells irradiatedat 0 C (D =1.7 Gy) are more ..sensitive to X raysthan cellB irradiated at 20°C (D =2.5 Gy). The rateof cooling does not markedly change the shoulder si-ze of the survival curve of CHO cells (D =0*49 Gyfor cooling rate (RCM C/min. | D *0.57 Gy forRC=0.6 C/min), in contrast with B16 melanoma cells(D =0.39 Gy for RC=4 C/min, and D,*1.16 Gy forRC*0.6 C/min). These results show that the increasein melanoma cell radiosensitivity at the low tempe-rature is not caused by thermal shock and that itis related to some, unidentified feeturea of mela-noma cells.

43

INCREASED MUTANT YIEID ON I£W DOSE-RATE ,f-EXPOSURE OFCHINSSE HAMSTER PETT.TfiN.E.A. Crompton, F. ZSlzer/ E. Schneider, J. KieferStrahlenzentrum der Justxis-Mebig-UhiversitSt,Giessen, Germany

Chemostat cultures of V79 Chinese hamster cells capable ofgrowing in suspension were exposed to Gcv-radiation at va-rious dose-rates and tested for the induction of 6-thioguanineresistance mutants. Mutation frequency was reduced at 50 inGy/hr, as also reported by others/ presumably of recovery fromsublethal damage. At lower dose-rates, 8 mGy/hr and 5 mGy/hr,the mutant frequency rose. At 8 mGy/hr the mutant frequencywas 4-fold higher than following an equivalent "acute" doseat 84 Gy/hr. Cytoflucmetric studies showed that this effectwas not related to cell cycle distribution changes in thechemostat cultures. It could be attributed to neither inductionof error-prone repair nor reduction of error-free repair as sochange in mutability of pre lew dose-rate exposed cells couldbe seen. At 5 mGy/hr mutant induction was approximately halfthat at 8 mGy/hr suggesting an "optimal" low dose-rate formutant induction.

44EFFECT OF WHOLE BODY IRRADIATION OF RATS ONCOLLAGiSNOLi'TIC ACTIVITY IN THBIR LUNGSA. M. DANCEtflCZ and If. M. JELEffSKAI n s t i t u t e of Nuclear Chemistry and Technology,War s za wa, Poland.

Mature, male r a t s of Wistar s t r a i n were exposed towhole body X-ray I r r a d i a t i o n with a dose of 6.5 Gy.They were s a c r i f i c e d in groups of f ive a t d i f fe rentime i n t e r v a l s up to one year a f t e r exposure.Anaesthesieed r a t s were subjected to lung lavagethrough t rachea and af terwards were s a c r i f i z e d bysever ing the abdomen a o r t a . The lungs were removedwashed and homogenized. The co l l ageno ly t i c a c t i v i t ywas assayed using 1-125 l a b e l l e d r a t skin na t ivecollagen as a substrate. The collagenolytic activityof lung homogenates and lung lavages from irradia-ted rats was compared with that of age-matched nonirradiated rats* Changes in irradiated rats had abiphasic character. Significant decreases of colla-genolytic activity In lung hotnogenates were obser-ved during the first ten days after exposure and2-3 months later. Similar fluctuations in collage-nolytic activity were recorded in lung lavagesfrom irradiated rats . 6 to 12 months after exposurethe collagenolytic activity in lungs of irradiatedrats was normalized with tendency to increase abovethe control value. The results obtained supplementbiochemical data relevant to meohanism(s) of deve-lopment of radiation-induced lung fibrosis.

45

ALANINE BASED DOSIMETRY - EXPERIENCE ANDAPPLICATIONSA. DAftfCKOVAFaculty of Nuclear Sciences and Physical Enginee-ring, PragueK. VACEKNuclear Research Institute, ftei, CSSR

Free radical concentration in alanine pellets(cylinder with 5 mm in diameter) determined by ESRspectrometry enabled to measure the absorbed doseby either gamma or electron irradiation in the10 Gy - 300 kGy dose range with the accuracy betterthan i 4.5 %• Low time and temperature fading,non-destructive reading, the possibility of dosisaccumulation, close tissue equivalency, etc.designate this system for radiotherapeutical endradiation technological dosimetry.

4.6EFFECT OF CONTINUOUS IRRADIATION ON SOME ENZYMESOF BIOSYNTHESIS OF FATTY ACIDS IN RAT LIVERI.flATELINKA, I. AHLERS, M. TOROPILAInstitute of General Biology, Safarik University,Koiice, Czechoslovakia

Male wistar rats were continuously irradiated onopen experimental gaaaa-field ( C o ) with dose ra-tes of 0.96, 0.57 and 0.19 Gy/d up to 35,90 and 120days. Activities of glucose-6-phosphate dehydroge-naae (EC 1.1.1.49), 6-phosphogluconate dehydroge-naae (EC 1.1.1.44), aalic enzyae (EC 1.1.1.40) andcitrate cleavage enzyae (EC 4.1.3.8) were elevatedover the entire tiae and displayed certain depen-dence on radiation dose used. Initial slight in-crease of aeetyl-CoA carboxylaae (EC 6.4.1.2) andactiv* part of pyruvate dehydrogenaae (EC 1.2.4.1)activities were followed by significant decreaseof their values at the end of the irradiation. In-creased activies of NAOPH producing enzyaes andcitrate cleavage enzyae created suitable conditi-ons for increase of fatty acids biosynthesis afterirradiation, which was described in literature. De-creased acetyl-CeA carboxylsse activity indicateathat probably it not the rate Halting enzyae offatty acida biosynthesis under these conditions.

47

THREE CLASSES OF DNA STRAND BREAKS AFTER X-IRRADIATION

E.DIKOMEY AND J FRANZKE

Institute of Biophysics and Radiobiology,University of Hamburg, Germany (F.R.)

Repair kinetics of DNA strand breaks were analysed in CHOcells. Cells were irradiated at 0 C with 3 or 9 Gy and subse-quently incubated at 37 C for various time intervals beforestrand breaks were analysed with the alkaline unwinding techni-que.

Repair kinetics after either X-ray dose was found to be com-posed out of three exponential components with different halftimes. Each component can be associated with the repair kineticsof a certain class of strand break. Component I and I I with thehalf times of T . * 2.3 and T n « 15 m1n and the in i t i a lfraction of f» = 0.70 and f . . * 0.25 are assumed to representthe repair of two different Classes of single strand breaks.Component I I I with t , , , * 150 - 200 min and f . . . = 0.05 areassumed to represent trie repair of double stranfl breaks.

48EFFECTS OF GAMMA RADIATION AND 5-BROMODEOXYURIDINEON THE FREQUENCY OF SISTER CHROMATID EXCHANGES INCREPIS CAPILLARISB. DIMITROV

The induction of SCE in Cr.Capillaris by gammaradiation and the effect of the amount of incorpora-ted! BrdU into DNA (unifilar and bifilar substituti-on) on this process has been studied by means of BrdU-labelling method. Both unlobelled cells and cellsthat hve been labelled with BrdU for either thefirst cell cycle or the first and second cell cycleswere irradiated with various doses (0.25-2.5 Gy)Co gamma rays.The data showed that irradiation before BrdU in-

corporation into DNA had no apparent effect on theSCE frequencies*Irradiation of the cells labelledwith BrdU for the first cell cycle either immediate-ly after the end of the cycle or 4 hours after thebeginning of the second one resulted in dose-relatedincreases of SCE rate. The increase was more pronoun-ced in the second case and most clearly expressed atthe lowest doses of gamma radiation. The cells label-led with BrdU for the two cell cycles were exposedto radiation in order to determine whether the amou-nt of incorporated BrdU influences the processes ofinduction of SCE by radiation. The elevation of thefrequencies of SCE over the control in this experi-ment is only slightly different from that observedin the cells labelled with BrdU for the first cellcycle. These results suggest that gamma radiationinduces lesions leading to SCE on^y when BrdU subst-ituted DNA was treated. There isn t enought indica-tion that the increasing effect depends on whetherunifilar or bifilar substitution was performed.

49

RADIOLYSIS OF AMIDES : STRUCTURAL EFFECTS IN PURE AND AQUEOUSLIQUID STATE.J. DE DONCKER, A.C. DUSAUCY and B. TILQUINUniversity of Louvain, Radiation Laboratory, Batiment Lavoisier,Place Louis_Pasteur, 1 -_B-1348_Louyain-la-Neuve1_Belgium

Radiolysis of amides helps to elucidate the effects of radia-tions on peptide bonds, i.e. proteins.

N,N-dimethylformamide (DMF : H-CO-N(CH ) ) and N-methylforma-mide (NMF : H-CO-NHCH.J were 7-irradiated in pure and aqueousliquid systems. Radiolytic products were separated by capillarygas chromatography and identified by a GC/MS procedure. Fromthe analysis of the deshydrodimers (form by the combination oftwo parent radicals), it appears that : 1) In the pure liquidphase, the radiolysis of NMF samples produces a restricted num-ber of deshydrodimers and DMF all dimer isomers.

2) For agueous NMF, nodeshydrodimer is detected in contrast to the preferential for-mation of one deshydrodimer for aqueous solutions of DMF.

The study is in progress; the first results indicate that dif-ferent radiolytic mechanisms are to be considered for this twoformamides and for other amides in general (B. TILQUIN et al.,7th Int. Cong, of Radiat. Res., A2-01, 1983, Amsterdam).

50

AN INTEBSPECIES COMPARISON OF RADIOPBOTECIIVEEFFICACY OF 3 : 1 COMBINATION /CM/ OF CYSTA-MUJE /C/ AND 5-METHDXYTBYFTAMIHE /M/

M; POSTAL . P. KONA , P. PETTREK

Purkyne Medical Research InstituteHradee Kralove^ CSSR

In mice the protective efficacy reached withi.m. injection of CM was the same as after i.p.pretreatment.Low i.m. doses /24 mg C + 4mg M pert kg/ provided a significant protection againstlethal total body gamma irradiation in mice andrats.

In beagle dogs and dwarf Cameroon goats aslight protection by this mixture was achieved.In guinea-pig8 and rabbits no signs of protectionwere present.

The CM dosage tolerated without serious sideeffects in dogs was compared in. other species,so that the drug dose per unit surface area wasnot taken into account.

51I RADIOPBOTECTIVE STUDIES WITH A MIXTURE OF CYSTAMIld(C) AND, 5-METHOXYTRYPTAMINE , (M )M. POSTAL. J. MEHGL. P. PETIREKPurkynft Medical Research Institute, Hradec Kr&ove*,!CSSR

The relationship between toxic (LD) and protec-tive (PD) doses in mice was analysed by means ofthe isobole method. In an optimal 3 C : 1 M combi-nation of both drugs injected i.p. simultaneouslythe index of interaction of free bases proved tobe on the LD 50/2 level 0.80(0,67-0,97) and follo-wing 10 Gy on the PD 50/30 level 2,50 (1,64-3,81)within the 95 % confidence limits. An unilateralrelative antagonism of the toxic effect of cysta-mine and a bilateral potentiation of the protectiveeffects of both drugs bas been established.

All mice protected by this mixture (total doses30-704 mg.kg"!) survived 9 or 11 Gy of wbole-bodygamma-irradiation. Following 30 mg.kg-1 the expo-sure corresponding to the 5 % probability of lethalaction was 8,45 (4,64-9,66) Gy.

At the level of endogenous spleen colony-formingunits in mice exposed to 7-14 Gy reduced doses ofboth drugs in the mixture appeared to be more effec-tive than the optimal dosage of C or M injectedalone. A linear or polynomial dependence of (log)colony-counts versus exposure bas been described.

52

SYNTHETIC OLIGONUCLEOTIDES : A NEW TOOL FOR THE ANALYSISOF DNA CHAIN BREAKAGE AND DNA STRUCTURE MODIFICATIONS.

A.M. DUPLAA*, G.V. FAZAKERLEY*, A. GUY*, W. GUSCHLBAUER*and R. TEOULE

* Service de Biochimie, Bát. 142, Département de Biologie,Centre d'Etudes Nucléaires de Saclay, F-91191, GIF-S/YVETTECEDEX (France)

+ Laboratoires de Chimie, Département de Recherche Fondamen-tale, Centre d'Etudes Nucléaires de Grenoble, 85 X, F-38041GRENOBLE CEDEX (France).

Synthetic oligonucleotides have been used to analyse theDNA chain breakage induced by ionizing radiation. Whenhomopolymers d(T)15, d(C)15, d(A)15 labeled with P-32 at the5' or 3-end, were irradiated, they gave rise to a new patternof shorter oligonucleotides. After alkaline treatment, therewere separated by polycrylamide gel electrophoresis. Theintensity distributions versus the base positions could bepredicted very accurately by computer calculation. This newmethodology paves the way to a more precise analysis of DNAchain ruptures. In another set of experiments, oligonucleo-tides containing N-6 methyl adenine were used to analyse theeffect of DNA methylation. A methylase specific for thesequence GATC (dam repair gene) appears to act with a lagperiod behind replication on newly synthesized DNA daughterstrands which are transiently unmethylated. The dammethylation is thought to be involved in strand discrimin-ation during post replication mismatch repair. 500 MHz- H-NMR and NOE measurements of d(GGATCC) and d(GG m ATCC)showed that near the melting point temperature, the singleand double strands of the N-methylated forms are in slowexchange. The preferred conformation of the adenine methylgroup, cis to N , hinders base pairing and destabilizes thedouble helix in the GATC fragment.

53

POST-IRRADIATION INACTIVATION, PROTECTION, AND REPAIR OF THESULFHYDRYL ENZYME MALATE SYNTHASE

H.DURCHSCHLAG, P.ZIPPER

Institute of Biophysics and Physical Biochemistry, Universityof Regensburg, FRG, and Institute of Physical Chemistry, Uni-versity of Graz, Austria

Malate synthase, an enzyme with essential sulfhydryls, wasinactivated by 2 kGy X-irradiation in aqueous, air-saturatedsolution. Irradiation was performed in the absence or presenceof various additives: formate, superoxide dismutase, catalase,substrates or analogues, salts. Changes of activity were reg-istered up to 60 h after irradiation, in the absence or pres-ence of specific scavengers added post radiationem. Moreover,repairs by addition of dithiothreitol (DTT) were initiated upto 60 h after irradiation. Both primary inactivation and post-irradiation inactivation, as well as the repair behaviour wasfound to be modulated by the additives: all additives (espe-cially formate, substrates, analogues) provided a protectionagainst primary inactivation; post-irradiation inactivationwas impeded or accelerated by the additives. Repairs by DTT ledto more orN^ss pronounced restorations of activity, even whenthey were initiated 60 h after irradiation. Our findings indi-cate that both scavenging and specific ligand binding are re-sponsible for the protective effects against inactivation. Acomparison with the results of X-ray induced aggregation ofmalate synthase (small-angle X-ray scattering, electrophoreses)shows that the radioprotective effects of additives against in-activation and aggregation are not necessarily the same.

54

RISK OF OSTEOGENIC SARCOMAS IN 224Ra OR 226Ra M0USEEXPERIMENTSDVORAK V*< SEDLA*K A., BUBENfKOVA" D. , KOFRANEK V.x/'Medical Faculty of Hygiene, Charles Univ., Sroba'rova

48, Prague,CSSR,Institute of Hygiene and Epidemiology, Prague, CSSR.Long-term experiments were carried out in which a

comparable time course of the mean skeletal dose wasachieved by multiple " 4 R a injections and a singleadministration of 226Ra. Different levels of exposureto both isotopes were used in other experiments. Themethods included dosimetric and biological characte-ristics such as survival curves, roentgenography,histopathology. The evaluation of the results was alsoperformed using the approaches of other authors expe-rimenting in bone surface and bone volume seekerstoxicity, e.g. the evaluation of the yields of osteo-genic sarcomas at 140 days before death, thus enablingto consider the results in a broader context. Our ex-perimental set up and the. use of one strain of micethroughout, identical housing conditions as well asthe methodology used provided realistic evidence thatthe risk of osteogenic sarcoma development is an orderhigher after 224R 3 a s compared to 226R 3.

55LOW-LEVEL GAMMA- AND NEUTRON-IRRADIATION EFFECTS ONVICIA FABA GROWTH AND CELL DIVISIONP.M. ECKLDivision of Genetics and Developmental Biology,University of Salzburg, Salzburg, Austria.

Seedlings of the broad-bean, Vicia faba L2»2were

irradiated at low gamma ( Co) and neutron ( Cf)dose rate (0.9 mGy/h) up to doses of 0.15 Gy.a) effects on growth: A slight but not significantincrease of growth rate was observed up to gamma-doses of 0.06 Gy. Following higher doses growthrate decreased again accompanied by a reduction ofthe individual differences evident from the stand-ard deviations. The 0.15 Gy value of growth rate,however, reflects no significant change compared tocontrol. Neutron-irradiation on the other hand ledto a significant increase after a dose of 0.02 Gy.With higher doses a nearly exponential decrease wasobserved which resulted in a significant growthrate reduction at 0.15 Gy. b) effects on celldivision: Mitotic activity as measured by themitotic index (MI) reveals marked fluctuations upto neutron-doses of about O.O6 Gy followed by acomplete cessation. Mitotic figures are again seenafter doses >0.11 Gy. Gamma-irradiation leads to asimilar effect which is, however, not as pronounced,also in the dose range from O.O6 to O.11 Gy mitosescould be detected. There was a minimum MI foundafter a dose of 0.08 Gy. Up to 90 minutes afterboth gamma-- and neutron-irradiation, marked time-dependent oszillations were found, which especiallyin the case of gamma-irradiation sometimes signifi-cantly exceeded the control-values.

56

EifLCl OF DITHIOTHREIIOL ON THE RADIATION INDUCED DNA BREAKSI\ HUMAN CELLS WITH DIFFERENT IN1RINSIC GLUTATH1ONE CONTENT

MARGARETA EDGRENDepartment of Tumor Biology II, Karolinska InstituteStockholm, Sweden

The protective effect of dithiothreitol (DTT) on theinduction of single-strand DNA breaks (ssb) by radiation wasinvestigated in glutathione-deficient (GSH~'~) and glutathione-proficient (GSH+'+) human fibroblasts. The yield of ssb wasdetermined with the alkaline unwinding technique. The dosereduction factors (DRF) indicating the extent of protection,were much larger for anoxically than for aerobically exposedcells with the exception at high DTT concentrations. Thisresulted in concentration dependent oxygen enhancementratios (OER). For GSH~'~ cells the OER gradually increased from1.2 (untreated cells) to a plateau value of about 3.5 at0.3 mM. For GSH"1"'"1" cells the OER increased from 3.5 (untreatedcells) to about 8 at 1 mM and thereafter decreased with DTTconcentrations higher than 10 mM. The increase in DRF whenexposures were made aerobically was similar for both GSH~'~ andGSH+'+ cells, and was in both cases linear up to a concentra-tion of 10 mM. When exposures were made anaerobically, lowconcentrations of DTT protected GSH~'~ cells more than GSH+'+

cells. By treatment with intermediate concentrations underanaerobic conditions, the DRF was about the same for the twocell strains. When high concentrations of DTT were used therewas a decrease in the DRF for GSH+/+ cells but not for GSH-/-cells. It was concluded that DTT acts both as scavenger ofOH" radicals under both aerobic and anoxic conditions, andas H-donor in competition with oxygen under anoxic conditions.

57

THE ENHANCEMENT OP REPRODUCTIVE CELL DEATH 3YPOSTIRRADIATION HYPOXIA AND LOW INTRACELLULAR r-~-:-

L.Kh.Eidus, L.N.Kublik, Yu.N.Korystov, A.I.I. Vexier

Institute of Biological Physics of the USSR ^cad.Sci. , Pushchino, Moscow Region, USSR

The survival of Chinese hamster fibroblasts ( -?-28, anaeuploid clone 431? 24 hour-old asynchronousculture) irradiated and then incubated under diffe-rent conditions of oxygenation and at varying intra-cellular pH's (pH^) was studied. The hypoxia wasprovided by replacing the normoxic nutrient Kiediumwith a hypoxic one prepared by adding sodium sul-fite (5»1O-3M) a day before the experiment. The re-quired pH-j_ was achieved by placing the cells intoa medium containing 0.1M phosphate-phosphate buf-fer, pH 6.0 or 7.0. Both the pbstirradiation hypo-xia and low pHi (6.0) are shown to increase thereproductive death of the irradiated cells. Thiseffect increased with the duration of the treatmentwithin 1-1.5 h. and declined as the time intervalbetween irradiation and the treatment increased.The results obtained indicate that under normoxiaa rapid repair of potential radiation lesions ofcells occurs whereas low pHi and hypoxia inhibitthe postirradiation repair of these lesions thusproviding their realization. It was also shown thatduring incubation of cells under hypoxic conditionsthe pHj. decreases. The suggestion is made that thisdecrease is responsible for the decline in cellsurvival under postirradiation hypoxia.

58

CHROMOSOME ABERRATIONS INDUCED IN HUMftN LYMPHOCYTESBY IDW DDSES OP CO-60 GAMMA-RAYS DELIVERED AT HIGHAND IOW DOSE-RATE.

L. Fahry, Cytogenetics Laboratory,Department of Radiobiology,C.E.N./S.C.K., 2400 Mol, BELGIUM.

Chromosomal aberrations in human lymphocytes nay beuseful in the assessment of the genetic risks of radiationexposure to man, particularly at low dose level. Numerousstudies have investigated the induction of aberrations afteran exposure to acute doses of ionizing radiation, but dataat low dose-rates are relatively scarse. For that purpose,human peripheral blood lymphocytes were exposed to low doses(0.1 upto 1 Gy) of Co-60 gamma-rays at low dose-rate (0.1Gy/h) and the results of chromosome analysis were comparedto those obtained after exposure to acute radiation doses(0.05 upto 2 Gy) delivered by a Cobalttherapy apparatus.Chromosome aberrations were scored in metaphases collectedafter a 44 h culture time to avoid scoring of seconddivision cells. In both cases, the frequency of dicentricscould be was best fitted to the linear-quadratic doseresponse model (YâD+bD' ), which supports the assumptionthat dicentrics may result frcm single or separate ionizingtracks. Tie a and b coefficients were respectively r*qual to3.96x10" \ and 2.48x10"L for low dose-rate, and 2.97x10"z and4.29x10"^ for high dose-rate. The little deviation in the acoefficient is probably due to the different range of dosesused in both cases, whereas the decrease of the bcoefficient reflects the fact that, at low dose-rate, thedose is delivered over an extended period of time for thehighest doses. This observation corroborates the previousfinding according to which the damages resulting from twoionizing tracks have to be produced within a short intervalof tine (approximately 5 h) to give rise to dicentricaberrations in human lymphocytes.

59DABK AND PHOTOCHEMICAL BINDING OP FUROCOUMARINS TOBNA- AND DNA-NUCLEOPROTEINS«7» FIDY, K. TOTH, A. FEKETE. Q. CSIK, K. FEH!§RInstitute of Biophysics, Semmelweis Medical Univ.Budapest, HungaryPossible dark binding of furocoumarins to nucleo-

proteins may increase the risk of the photochemicalPUVA therapy applied in skin diseases. The dark in-teraction using 4,5', 8-trimethylpsoralen (TMP) and4 - aminomethyl-TMP-hydrochlorid (AMT) as reagentsand T7 or MS2 phages and their nucleic acids assubstrate were studied by fluorescence spectroscopyand optical melting techniques. Dark mutagenic acti-vity in case of a series of psoralen derivativeswas checked through phage multiplication in hostbacteria. Irradiation to induce photochemical bin-ding was performed by a 2500 W Xenon lamp - mono-chroma tor system. In vitro studies showed a strongbinding of AMT in low ionic strength buffers whatis partially inhibited if proteins are present. AMTis mainly intercalated in case of DNA substrate butin case of RNA outside binding may also be signifi-cant. The overall association constant of AMT isfour times higher for MS2 than for T7. The complexcan be totally dissociated, thus it does not causemutagenic effects in vivo - as it was shown by bio-logical activity studies. In case of electricallyneutral psoralen substituents no significant darkmutagenicity was detected. Irradiation at 365 nmup to about 5 kj/m leads mainly to singly dimeri-zed products of nucleotide bases and the furocouma-rins; at higher doses cross-linking takes place.The wavelength dependence of the reaction was cha-racterized as by optical as by biological activitymeasurements.

60

INFLUENCE OF ENDOGENOUS GLUTATHIONE CONTENT ON THEINDUCTION AND REPAIR OF DNA DOUBLE-STRAND BREAKSD.Frankenberg*, M.Kistler , F.Eckardt

Gesellschaft fiij Strahlen- und Umweltf orschung,*Frankfurt and Neuherberg, F.R.G.

Haploid and diploid glutathione (glu) deficientyeast mutant cells were irradiated with 60-Co-gamma-rays under aerated and anoxic conditions to evaluatethe influence of the endogenous glu content on theinduction and repair of DNA double-strand breaks(DSB). In the yeast system a DSB can be consideredas a potentially lethal lesion, i.e. a DSB becomeslethal if not repaired. Since stationary haploidcells are not able to repair DSB, the Do-value oftheit exponential survival curve corresponds to thedose for the induction of in the mean one DSB percell. Under aeratee conditions haploid wild type(wt) (100% glu) and haploid mutant cells (20%, 7%and 4% glu respectively) have identical Do-values.This indicates that the induction of DSB is not in-fluenced by the endogenous glu content. However,under anoxic conditions the Do-values decreasedwith decreasing endogenous glu content. The OER-values for the induction of DSB in wt-cells and inthe mutants containing 20%, 7% and 4% of the wt-glucontent are 3.6, 3.6, 2.2 and 1.8 respectively.Irradiation of diploid wt (100% glu) and mutant(7.5% glu) cells under aerated or anoxic conditionsyielded an OER-value of 2.6 for both cell lines.In wt-cells, DSB which are induced under aeratedconditions are repaired more easily than thoseinduced under anoxic conditions. However, in gludeficient mutant cells DSB induced under aeratedconditions seem to be somewhat less reparable thanthose induced under anoxic conditions.

61THE EFFECT OF CYSTEINE ON THE YIELD AND REPAIR OFRADIATION-INDUCED DNA DOUBLE-STRAND BREAKS IN YEASTM.FRANKENBERG-SCHWAGER, D.FRANKENBERG, R.HARBICH

Abteilung Biophysikalische Strahlenforschung derGSF, Frankfurt, F.R.G.

The concept of indirect radiation action impliesthat the products of water radiolysis - mainly OHradicals - are responsible for conferring lethaldamage to the DNA of irradiated cells. The protec-tion of sulfhydryl compounds against the lethal ac-tion of radiation is explained by their capabilityto scavenge radicals und thus preventing damage in-duced into the cellular DNA. There is convincingevidence that in yeast the DNA double-strand break(DSB) is the critical primary lesion leading to celldeath after irradiation with ionizing radiations.The induction of DSB in anoxic yeast cells by 60-Co-gammarays was studied in the presence of cysteine.Preliminary results suggest that the inductionfrequency for DSB is not decreased by 0.4M cysteine.This result seems to indicate that the "protection"by cysteine of cells against the lethal action ofradiation may not be due to the prevention of DSBbut rather due to the promotion of their repair.Experimental support for this interpretation comesfrom two findings: 1. After incubation of yeastcells with cysteine their lag-phase is prolongedproviding additional time for the repair of radia-tion induced critical lesions. 2. The same "pro-tecting" effect on cell survival by cysteine can beobserved if cysteine is present during or onlyafter irradiation of cells.

62

INFLUENCE OF HYPERTHERMIC TREATMENTS ON THE REPAIR OF

X-RAY INDUCED DNA STRAND BREAKS

J.FRANZKE, E.DIKOHEY

Ins t i tu te of Biophysics and Radiobiology,University of Hamburg, Germany (F.R.)

Repair kinet ics of X-ray induced DNA strand breaks inCHO cel ls were measured af ter d i f ferent hyperthermictreatments. Cells were i r radiated with a dose of 9 Gy atO"C a) without heat treatment, and b) a f ter a preceedingheat exposure at 43"C for 20-60 min. or af ter a preceedingheat exposure for 20 min. a t 42-45#C. DNA strand breakswere measured with the alkal ine unwinding technique.

a) For X-rays alone, i t could be shown that repairkinet ics is composed out of three exponential components;each component represents the repair kinet ics of a certainclass of DNA strand breaks.

b) Heat treatments applied did not a f fect the strandbreak ef f ic iency fo r X-rays, but repair k inet ics of X-rayinduced DNA strand breeds were found to be modified. Fora l l three classes of strand breaks, half time increaseswith ei ther increasing time of exposure at 43*C or withincreasing temperature when exposed for 20 min. Heat didnot af fect the f rac t ion of repair component I I I . In contrast,f rac t ion of component I I was found to increase withincreasing time of exposure as well as with increasingtreatment temperature. Fraction of component I decreases i nthe corresponding manner.

63

EFFECT OF MIXED LIGAND CHELATE THERAPY ON THEREDUCTION OF NIOBIUM AND CERIUM IN MICE

A. GACHALYI. 3. NAMENYI and L.P. VARGA

"Frederic Doliot-Curie" National Research Institutefor Radiobiology and Radiohygiene,Budapest.Hungary

In the experiments connecting to the preventionand treatment of radioisotope internal contami-nation, primarily specific methods are used for thedecrease of the retention of radiometals and theincrease of elimination. However, the data forisotope-mixture contamination and the efficiencyof decorporating agents given simultaneously arerather incomplete.

In nuclear reactions, primarily in fission

eroducts occuring during the nuclear weapon tests,*Nb and 144Ce are present in 4.9-6.2 %. Therefore,animal experiments were undertaken in order todetermine how the deposition and elimination ofthese radiometals can be altered beneficially withthe administration of complex forming compounds insingle or combined treatment forms.

From our results i-t-.9an be stated that themobilization of 95Nb+-*-44Ce can beneficially beperformed with simultaneous adding of specificagents /i.e. desferrioxamine-B; Na3Ca-dietilene-triaminepentaacetic acid/ without decreasing theefficiency as compared to the separate application.

64THE PREFERENTIAL INITIATION OP UNSCHEDULED DNA SYN-THESIS AT THE NUCLEAR MATRIX OF IRRADIATED CELLS

A.Gaziev, V.Bezlepkin, Y.Malinovsky, V.Velcovsky*

Institute of Biophysics, USSR Academy of Sciences,Puschino, Moscow Region, USSR; *Institute of Bio-physics, CSSR Academy of Sciences, Brno, CSSR

We have studied the distribution of unscheduledDNA synthesis (UDS) in the nuclear matrix (NM) andbulk chromatin of UV(254 nm)- and ]f( Co irradiat-ed Zajdela hepatoma and rat liver cells. In the MI ofirradiated hepatoma and liver cells a higher level(3-40-fold) of hydroxyurea-resistant UDS has beenobserved in the initial short period of time (1.5--5 min) of postradiation incubation if compared tothat of bulk chromatin. Compartment alizat ion of en-zymes and factors involved in UDS and also the pre-ferential availability of the NM DNA damaged sitesfor the repair enzymes can be assumed to serve asan explanation of the phenomenon has been discove-red. Both DNA polymerase oC and DNA polymerase /J areshown to participate in UDS at the NM of thes cells.DNA polymerase /J is more firmly attached to the NMof normal liver cell than to that of regeneratingliver and hepatoma cell. Poly(ADP-ribose)synthetaseactivity is shown to be associated with the NM. In-hibition of this activity results in increase ofthe UDS in NM of irradiated cells.

65

THE xiADIOSSNSITIZIKG EFFECT OF ACETONE AT VARIOUS

OXYGEN CONCENTRATIONS

G.L. GAZSO, A . DAM

'FJC""'Natl.Res.Inst.for RadiobioLand Radiohygiene,

Budapest, Hungary

The radiosensitizing effect of acetone was

investigated in Bacillus mepaterium spores.

Experiments were done in aqueous and non-aqueous

liquids with four oxygen concentrations (1OO# No,

0.7$ 02, 1.2# 0 2 and 2.1% 0 2 in N 2 ) . Under anoxic

condition the extent of sensitization increases

with increasing acetone concentration up to a

maximum seen at around 14- mole/litre. Increase of

oxygen concentration shows a decreasing tendency

in sensitization. The radiosensitizing action

of acetone is due to the scavenge of hydrated

electron.

66

TIME-DOSE-RELATIONSHIPS AT HIGH-DOSE-RATEAFTERLOADING IN GYNECOLOGICAL TUMORTHERAPY

F.H.GLASER. D.GRIMM, K.-H.HEIDER

Klinik u. Poliklinik f. Radiologie d.MedizinischenAkadetnie Erfurt, und Radiologische Klinik u.Poli-klinik d. Martin-Luther-Universitfit Halle/S.,DDR

For high-dose-rate afterloading in gynecologicalradiotherapy an adequate fractionation with reducedtotal doae ie necessary considering the basicallychanged dose-time-relation opposite to the commonlong-time brachytherapy.At first we tested 19 vari-ousfractionation schedules differing in dosage,number of fractione and treatment time to find outthe compatibility for normal tissue of bladder andrectum.In addition calculations of equivalent dosesseem to be recommendable by means of mathematicallyformulated model conceptions according the NSD-formula.Changed exponents p for the number of fractions N depending on the overall treatment time wereused for the ret-calculations at low fractionatedsmallvolume brachytherapy opposite to a higherfractionated external beam therapy the NSO-conception was developed for.Our calculations were basedon a ret-value of about 1,800 ret for 60 Gy incommon brachytherapy.The results show in connectionwith clinical and histological tuaor control inmore than 2,500 patients in over 10 years that 5 to6 fractions in weekly intervals,overall treatmenttime 28 to 35 days, with 7 Gy per fraction in pointA and total doses of 35 to 42 Gy are hidiy effectivein tumor control and also show a statisticallysignificant decrease of radiation induced side-effecte at bladder and rectum.

67GROWTH KINETICS OF HAEMOPOIEHC STROMAL PRECURSORSAFTER LOW DOSE GAMMA IRRADIATION

J.GIDALI. I.FEHER, B.KANYAR

"Frederic Joliot-Curie" National Research Institutefor Radiobiology and Radiohygiene, Budapest, Hungary

Murine bone marrow derived fibroblastic colonies/CFU-F/ are regarded as part of the haemopoieticstroma. In order to obtain information 6n the effectof relatively low dose V irradiation on the CPU-Ppopulation, in vitro radiosensitivity of CPO-P wasdetermined and growth kinetics of CPU-P from bone•arrow of normal or 0,5 Gy irradiated BDF-, mice werecompared. Since we found a strict correlation betweencell count and surface area of CPU-P .colonies, clonesize of CFU-P colonies was determined by surveyingtheir surface area. Data obtained-indicated hetero-geneity of normal CPU-P population: calculatedpopulation doublings in 7 day old orflociee variedfrom 5.9 to 8.0 suggesting that CFU-F populationconsist of various subpopulations with variousdoubling capacity. Radiosensitivity of thece sab-populations proved to be different, too. 0.5 Gy invivo T irradiation did not reduce significantly thefemoral CFU-P content. The reduction was quickly re-stored and a significant overshoot was observed 10-11weeks after the exposure. Transient changes in theratio of CFU-P subpopulations and a slightlyincreased doubling time of CPU-P from 0.5 GyIrradiated nice may be responsible for this lateovershoot.

68

DNA-DISTRIBUTION OF CARCINOMA OP THE ENDOMETRIUKBEFORE, DURING AND AFTER HIGH-DOSE-RATEAFTERLOADING IRRADIATION

D.GRIMM. I.GRIMM, F.H. GLASER, R.A.WEIDHASE,J.SCHINDLER

Klinik u. Poliklinik f. Radiologie d. MLU Halleund d. Medizinischen Akademie Erfurt,Lehratuhl f. Industrietoxikologie d. MLU Halle,Institut f. Biochemie d. Pflanzen d. AdW Halle,DDR

The extent of ploidy and DNA-distribution of car-cinoma of the endometrium of various degrees ofmalignity were recorded by flow-cytofluorometrymeasurements before, during and after high-dose-irradiation of iridium.As the histological degree of differentiation isdecreased, a change in the pattern of the celldistribution from dipôid to aneuploid can be detec-ted.Before the therapy, an increased proportion of S-and (Gp+M)-phases in relation to the normal tissueof the uterus is to be noted.As the numbers of treatments increases, and towardsthe end of the therapy, these are increating signsof cell necrosis on the histogram and from thehi8topathological result.Should the proportion of the S- and (Gg+Mj-phases,at the end of the therapy, be insignificant inrelation to the original findings, further therapymust be considered.

69

X-RAY AND CYTOSINE-ARABINOSIDE /ARA-C/ INDUCEDCHROMOSOME ABERRATIONS AND UNSCHEDULED DNASYNTHESIS IN THE Gl-PHASE OF THE CELL CYCLE

S. GUNDY, L. P. VARGA and M.A. BENDER1*

"Frederic Ooliot-Curie" National Research Institutefor Radiobiology and Radiohygiene,Budapest.Hungary

*Brookhaven National Laboratory, Medical Department,Upton NY. USA

Chromosomal aberrations of 2 Gy irradiated humanperipheral blood lymphocytes were studied aftervarious intervals of phytohemagglutinin stimulation.There was no increase in deletion yields for inter-vals up to 8-12 hr but rings and dicentrics in-creased by about 50-60 % in the interval between 0and 8 hours. Induced unscheduled DNA synthesis wasalso measured during the same interval and wasfound an elevated level during the first 6 hrs.Incubation of human blood lymphocytes with Ara-C

following either Go or Gj X-irradiation caused asynergistic increase in both deletion andexchange aberration frequency, however somevariability of Ara-C-effect was found among donors.Due to the synergistic effect, Ara-C is believed

to inhibit the repair of DNA damage induced byX-rays. The difference found in the rate ofincrease in the frequency of chromosomeaberrations suggests some individual variabilityin the repair capacity of human lymphocytes.

70

RESPONSES TO SUBLETHAL DAMAGES OF CHO-CELIS IN COLONY SIZEDISTRIBUTION

G.K. HAGEHAHN, C. LIPFERT, G. WtlPPEN

Medisinische Hocbschule Hannover, Hannover, F.R.G.

Colony s i e e d is tr ibut ions we have used to analyse s p l i t

dose e f fec t s on surviving c e l l colonies of ionis ing radiations

in comparison to colony survival f rac t ions . Tor sub le thal

damage repair (SLDR) we expected from preliminary resul ts

(iVth Int . Conf. Med. Phys . , Ottawa, 1976, 6 . 9 ) , e f f ec t s only

on survival fract ions and, analogous to our PLDR experiments

(iBth Ann. Meet. E.S.R.B., Zurich, 1984, Abstr. p. 19) not on

colony s i z e d i s tr ibut ions . Two experiments were performed:

SLDR in dependence on dose in the region from 6 to 15 Gy and

on incubation time a t 12 Gy. Cells were synchronized by mito-

t i c s e l e c t i o n and irradiated by 200 kV X-rays 3 h l a t er with a

single dose or a f irst sp l i t dose and after a sp l i t time of3 h with the second sp l i t dose. Colony survival ratios forspl i t to single dose survival have values up to 5 - 6 whereasthe corresponding colony size distributions show no signif i-cant differences. The Median eolony s i te differences (KCD)between controls and irradiated cultures as measure for theunderlying radiation damages increase linearly with the incu-bation time up to 19 divisions of the controls and are inde-pendent on dose fractionstion. Prom these and the former re-sults we conclude that the heritable ce l l damages leading toMCD are independent on SLDR and PLDR.

71COMBINED ACTION OF SMALL ACTIVITIES OF RADIO-ISOTOPS AND CARCINOGENS ON THE PROCESS Of TU-

MOR INDUCTION

S.HAMBARIZUMIAN, S.PAPOYAN(Institute of Radi.obiaJ.ogy ARMENIA)

The work intended to study the carcinogenic actionof small activities (0,0025-0,01 mc/gr) of iodine,strontium, phosphorium,and X-ray in combinationwith chemical carcinogens-^,4-benzpyren, 7t12-di-methyl-benz(a)-anthracen in different animal spe-cies.It was pointed out that upmentioned activities ofstrontium,iodine,phosphorum,and X-ray (one rad aday) used alone can not induce experimental tumorsin different animal species (mouse,rat,rabbit).In case when both agents (isotops and chemical car-cinogens) were used tougether it has been estimatedinduction of experimental tumors in different spe-cies.The result of experimentspoint out the validity ofanimal experimentation for the study combined ac-tion of possible carcinogenic chemicals and radio-active isotopes*

72

HIGH-LET RADIATION AND HIGH-LEVEL DOSIMETRY

J.W. Hansen K.J. OlsenRiS0 National Laboratory University Hospital

of CopenhagenDK H000 Roskilde, Denmark DK 2730 Herlev, Denmark

High-LET irradiation is usually not considered in the con-text of high-level dosimetry. Interaction of high-LET radia-ion fields with materials implies, however, that even thoughaverage doses to the material are low, there are locallyregions of high doses. In high-LET irradiation each particlehas a separate track, and the tracks do not overlap unlessvery high average doses are used. Calculation of the dosedistribution in a heavy-ion particle track shows that thedose range covers several orders of magnitude. This highlyinhomogeneous distribution of dose results in that measure-ment of average absorbed dose no longer suffices to describethe response, as the correspondence between average absorbeddose and its effects is without immediate coherence. Theintegral response to this energy deposition may be calcu-lated by using a theory, which requires knowledge of thelow-LET dose-response of the material from very low dosesand up to saturation. We have investigated two radiationdetectors, alanine and a radiochromic dye film, by irradia-tion with 60Co Y-rays, fast electrons, and ions covering arange in LET from 30 to 20200 MeVcmVg. Experimental find-ings have been compared with theoretical predicted dose-response data, and agreement within the experimental uncer-tainty has been obtained at doses below saturation (Hansen,Ris0-R-5O7, Rise National Laboratory, Denmark, 198*1).

73

AMELIORATION OF LATE RADIATION ENTEROPATHY BY PANCREATIC DUCTOCCLUSION

M HAUER-JENSEN, T SAUER, T BERSTAD, K NYGAARDUniversity of Oslo, Departments of Surgery and Pathology,Ullevaal Hospital, Department of Surgery, The NationalHospital, Oslo, Norway.

Absence of pancreatic proteolytic enzymes from the smallintestine has been shown to ameliorate the acute intestinalradiation syndrome. Although the pathogenesis of late radia-tion enteropathy differs from that of the acute changes,there is evidence to suggest an association between thedegree of mucosal changes and the extent of late intestinalwall fibrosis. The aim of the present study was to investi-gate the effect of a temporary exocrine pancreatic insuffi-ciency at the time of irradiation on the development of lateradiation enteropathy. In 72 female Wistar rats (groups of 6)a 10 cm long exteriorized mid small intestinal segment was X-irradiated with 19 Gy or 21 Gy 3 weeks after pancreatic ductocclusion or shamoperation. Radiation injury was assessedsemlquantitatively 2,8 and 26 weeks after irradiation usingone macroscopic and 7 histopathologic parameters. Two and 8weeks following irradiation there was no difference in thedegree of radiation injury between pancreatic duct occludedand shamoperated animals. However, 26 weeks after irradiationall parameters of radiation injury except the degree ofvascular sclerosis were less pronounced in pancreatic ductoccluded rats than in controls. It is concluded that theexocrine pancreatic secretion may influence the developmentof late changes following irradiation. Furthermore, sincethere was no correlation between the degree of vascularsclerosis and the other changes, our results suggest that thedevelopment of late radiation enteropathy is not secondary tovascular injury.

SIMULATION OF THE POSTIRRADIATIOH DAMAGE OF A STEMCELL POPULATION

F. HAUSER. E. NEC" AS*

Hybrid Computation L.ab. USLOZ, 128 OC Prague,Czechoslovakia and Dept. of Pathophysiology,Faculty of Medicine, Charles Unive ""sity,128 00 Prague, Czechoslovakia

Recovery of murine pluripotent hematopoieticstem cell (CFU-s) population from irradiation in-jury was studied by computer simulation. The si-mulation model includes a hypothetical feedback byvhich DNA-synthesizing CFU-s influence proliferat-ion rate in the CFU-s population. Response to do-ses of 1.5 and 2.6 Gy was simulated. The lower do-se kills 90 % of CFU-s and causes periodic increa-ses in proliferation rate. The higher dose killsup to 98 % of CFU-s and at the beginning causesexponential growth of the CFU-s population. Afterreaching 15-20 % of its normal size, however, theCFU-s population again exhibits periodic changesin Droliferation rate. In both cases the recove-ry lasts two weeks. The model adequately reprodu-ces complex proliferation kinetics observed in realexDeriments.

75

FRACTIONATED NEUTRON AND PHOTON IRRADIATION INTHE RIGHT LUNG OF YOUNG PIGS

TH. HERRMANN, L. VOIGTMANN, A. KNORR, J. LORENZ,K. WELKER, M. JOHANNSEN

Department of Radiotherapy of the Clinic ofRadiology, Medical Academy "Carl Gustav Carus"Dresden, GDR

Experiments on 73 young pigs (20 - 25 kg) aredescribed, in which the right lung was irradiatedwith neutrons (6/2 MeV-Cyclotron) or photons(60 Co) in 5 fractions in 5 days (n = 22,f = 24animals) or in 35 days (n = 15,jr - 12 animals).The dose distribution was calculated individuallyby an irradiation planning system because of thesize of the pigs. The histological findings andthe estimation of hydroxyproline in lung tissuewould be used as endpoint criterion in addition toclinical and x-ray investigations. The RBE-value is given in an organ related (the rightlung included) isodose being comparable in bothradiation forms. The RBE-value on the ED5o~levelfor 5 fractions in 5 days is 4,O (3,65 - 4,92,95 % confidence intervall) and for 5 fractions in35 days 4,1 (3,7 - 4,5). On this level daily dosesof 0,9 Gy neutrons or 3,8 Gy photons in the right-lung-included isodose were given.

76

G2 DELAY OF V79 CELLS EXPOSED TO HEAVY IONS FROM NEON TO URANIUML. Hieber and G. Kraft +

Institut fur Med.Strahlenkunde, D-87OO WGrzburg, FRG+ Gesellschaft fur Schwerionenforschung, D-6100 Darmstadt, FRG

Exposure to ionizinq radiation delays mammalian cells in theprogression through their cell cycle. Sparsely ionizing radia-tion (X- or y-rays) delays cells in the S and G2 phase. In con-trast, the delay after exposure to densely ionizing radiationlike 241-AM a-particles (LET = 120 keV/ym) is expressed in a pro-nounced arrest in G2 phase (Lticke-Huhle et a)., 1982, Rad.Env.Biophys., ££,171).

We now have studied changes in the cell cycle of V79 cellsafter exposure to heavy ions from neon to uranium, correspondingto LET values from 270 to 16,000 keV/ym. The cell cycle progres-sion was measured by flow cytometry (Phywe ICP22).

There is an increasing accumulation of the cells in G2 withincreasing fluence (particles/cm2) for all ion beams, but withsteeper slopes for ions of higher energies. On the other hand,the effiency of the particles decreases with increasing atomicnumber and LET. In addition, the time course of the accumulationin G2 is dependent on the particles used. For lighter ions (Ne,Ar) the max. G2-fractions are obtained 10 to 12 hours after ex-posure. Up to 20 hours are required for the maximum effect afterPb or U treatment.

For the differences in the time course there are two explana-tions.(i) The energy deposition of very heavy ions is so high that noprogression in any phase occurs during the first hours.(ii) A part of the energy deposited is wasted before a possibledamage and therefore only a fraction of cells are blocked beforemi tosi s.

77MORPHOLOGY OF RAT HEMOPOIETIC TISSUE ONE YEAR AFTERWHOLE-BODY IRRAOIATION (DOSE OF 4 GY) WITH DUCoGAMMA RAYSM. HOFER. L. TKADLECEK. §. VIKLICXA. Z. KARPFSLInstitute of Biophysics, Czechoslovak Academy ofSciences, Brno, CSSR.B. S. FEDORENKO. R. A. KABICYNA. A, N. KABACHENKOInstitute of Medical and Biological Problems,Ministry of Health, Dubna. USSR.

6ORats were irradiated with Co gamma rays (whole-

body dose of 4 Gy). After one year, the bone narrow,inguinal lymph nodes and the spleen were removed,fixed, embedded and sectioned for light and elec-tron microscopic investigation. Thus, the condi-tions of our experiment differed from those presen-ted by Viklicka et al. at this (19th) AnnualMeeting of the ESRB only in the sort of radiation.Repair of acute changes was complete when the space,occupied by the active and inactive bone marrow(fat cells), was compared in irradiated and controlanimals. The morphology of the red pulp in thespleen sections of control and irradiated rats wassimilar, too* Striking differences were found be-tween the morphological picture in lymph node sec-tions: one year after irradiation, the lymph nodu-les were smaller and fewer in number. The sinuseswsre dilated and contained fewer lymphocytes. Onthe contrary, the quantity of reticular and colla-gen fibres was increased in lymph nodes of irradia-ted rats* Then, no conspicuous difference was foundin the degree of repair of different hemopoietictissue one yeaj-Qafter whole-body irradiation (doseof 4 Gy) with Co gamma rays or 4 GeV/nucleonhigh-energy helium ions.

ABSTRACT REPRODUCTION FORM78

REPAIR OF X-IRRADIATED MOUSE CELLS IN HETEROKARYONS!AND SYNKARYONS3. Hofaeôvd. V. SpurniInstitute of Biophysics. Czech. Acad. Sci., Brno,Czechoslovakia

The capacity of cell fusion and DMA synthesis iniheterokaryons formed by fusion of mouse L fibro-blasts and mouse lymphosarcona LS/BL cells wasstudied. Prior to fusion, either one or both lineswere X-irradiated (doses of 5 and 20 Gy). In bothcases the frequency of heterokaryon formation incultures with irradiated cells was higher than thatin the non-irradiated control populations* Autora-diographic analysis based on 3H-thymidins incorpo-ration showed pronounced inhibition of DNA synthe-sis in the irradiated cells cultured separately,and a significantly higher number of nuclei capableof DNA synthesis in the heterokaryons. Hetero-karyons had also more nuclei of irradiated cellswith unscheduled DNA synthesis. Hybrid cells (ayn-karyons) obtained by fusion of Irradiated (5 Gy)and non-irradiated mouse cells, differed from the ;parent lines and from the hybrid cells of non-irra-diated parents in their morphological, growth andkaryological properties. Unlike the irradiatedparental cells, these hybrids were capable of per-manent proliferation in vitro. Chromosomes of theirradiated parent line were preferentially elimi-nated from the karyotype of the hybride. It may besupposed from our results that a certain recoverytakes place in the cells damaged by ionizing radia-jtion on the basis of cooperation and interactionwith other cells in heterokaryons or synkaryons.

79

EFFECT DP WHOLE-BODY GAMMA. IRRADIATION ON LIVER MICRO-SOMAL PROTEIN SYNTHESIS OF VITAMIN-E DEFICIENT RABBITSJ.HOLLAND. L.KSROSI.GYONGYI MANGEL,GY.KATONA ANDL.JD.SZABd'FJC'Natl.Res.Inst.for Rad.biol.ahd Rad.hyg.Budapest,Hungary

Vitamin-E exerts a significant antioxidant effectin the living organism. Its lack increases peroxida-tion processes of different origin, especially thoseinduced by ionizing radiation in the presence ofoxygen.

As shown earlier, 6-12 hr after 3-6 Gy whole-body gamma irradiation the protein synthetic activ-ity of liver microsomes isolated from rodents inrcreases. This time the effect of E-vitamin deficiencyon the radiosensitiyity of membrane-dependent pro-tein synthesis was investigated. Cincilla rabbitswere kept on E-vitamin deficient diet ODlet'group)till weight stagnating state (4—5 weeks). Controlgroup was fed with the same diet but supported byvitamin-E (5 mg/kg body weight; 'Control•group).The third group of rabbits was kept on normal-standaJcLdiet (*Normal'group). Rabbits prepared thus weresacrificed 8 hr after 3 Gy 6oCo-gamma irradiationand microsome and cytosol fraction were prepared fromthe liver by ultracentrifugation. Microsomes andcytosol-pH5-fraction derived from different experi-mental group of animals were combined in a cell-freeprotein synthesizing system and ^C-amino acid in-corporation was measured. It was stated that E-vita-min deficiency decreases the intensity of proteinsynthesis to such an extent (first of all due tothe inhibitory effect of tRNA+synthetase system)that the increase of incorporation induced by radia-tion remains very slight.

80

BIO-DOSIM1STRIC 3VALUATI0N OP RADIATION LESIONSIN EXPERIMENTALLY IRRADIATED GOATSEmiliâ Horsid, R. Klj8ji6, Z. MilosevicDepartment of Radiology of Veterinary Faculty7I000 Sarajevo, Yugoslavia

In this report the bio-dosimetric evaluationis presented of the radiation lesions in experime-ntally irradiated goats with highly energeticX-rays with the dose of 2#oo and 2.6o Gy.

The evaluation was carried out the basis ofstructural chromosome lesions in lymphocytes ofperipheral blood 24-, 72 and 168 hours followingirradiation,

Hesults indicate that the degree of structu-ral chromosome lesions is in proportion to thedose of irradiation.

81

EFFECT OF AET, CYSTEAMINE AND WE-2721 OK THE PROS-TACYCLIN FORMATION OF RAT AORTA, ARACHIDONIC ACIDAND ADP INDUCED PLATELET AGGREGATION

Gy. Horvath and G7. Benk6

,,Frederic-Joliot Curie" Natl. Res. Inst. for Radio-biol. and Radiohyg. Budapest, Hungary

In the cardiovascular affects of AET and cys-teamiae direct effects made on blood vessels andmicrocirculatioa are playing an important role, toa jThese two compounds, but not WR-2721 both in vitro |and in vivo decreased prostacyclia (PGI-2) forma-tion of rat aorta ring* and also inhibited the ara-chidcmic-acid (AA) and ADP induced platelet aggre-gation. In order to get answer on what part of AA- \cascade exert their effect 01, indomethacin was \used as reference in these experiments. j

Parts of thoracic aorta were incubated in Tris ibuffer containing indomethacin, AET or cysteamine. ;These pre-treated aorta rings were incubated inplatelet-rich plasma in which thromboxane synthesiswas inhibited by imidazole. Na-AA was applied asprecursor, PGI-2 formation was determined by plate-let aggregation bioassay. PGI-2 formation was dec-reased by all three compounds, but not by WR-2721. |Adding Na-AA precursor PGI-2 formation sygnificant- jly increased in the indomethacin., AET and cystea- jmine treated aorta rings. It means that they could (use PG-endoperoxides originated from platelets for >their own PGI-2 synthesis, ie. prostacyclin synthe- ?tase was not inhibited. I

Non-steroidal anti-inflammators among them ,|indomethacin are known cyclo-oxygenase inhibitors.According to our results it is supposed that AETand cysteamine are potent cyclo-oxygenase inhibittors, while WR-2721 has no effect on it.

PHOTOBIOLOGY OF FUROCOUMARINS AND THEIR INTERFEREDCE WITH THE DEVELOPMENT OF BACTERIOPHAGE LAMBDA

Z. Hradedna. L. Kittler


Zentralinstitut fur Mikrobiologie und experimen-telle Therapie, Akademie der Wiesenschaften derDDR Sena, DDR

It was shown that the multiplication of phagelambda was strongly supressed by furocoumarinsafter irradiation with near ultraviolet light of365nm wavelenght. Using xanthotoxin or angelicinthere was a narked inhibition of the phage DNAinjection and replication but adsorption was un-affected. This Inhibition was attributed to var-ious types of DNA crosslinking produced in thephage heads* Type I crosslink corresponded to co-valsnt binding between adjacent sites in oppositestrands of the double helix. Crosslink type 11//hairpin crosslink/required a highly condensed DNAand corresponded to covalent binding between ad-jacent sites on double-helical segments of foldedDNA molecule. The relationships of the type Icrosslinks to the DNA replication and of the typeII crosslinks to DNA injection are being discus-sed* Like type II crosslinks, the nucleic acid -- protein crosslinks hinder injection.

83

FORMATION OP DOUBLE-STRAND BREAKS IN E.COLI BY IONI-ZING RADIATION AND THE INFLUENCE OP CYSTEAMINEJ.W. HULSEWEDE & D. SCHULTE-PROHLINDEMax-Planck-Inst. f\ Strahlenchemie, Mil 1 he im/Ruhr,West Germany

The survival of Escherichia coli B,stat-phase cells,was measured by immediate plating at 37 C, follo-wing Co-y-irradiation for 15 min at 18 C, underair, nitrogen or nitrous oxide and in the absence orpresence of 10 M cysteamine. Cysteamine shows aprotecting effect under all conditions with a dosemodifying factor between 1.3 and 1.8. Under the sameconditions sedimentation measurements of the in vivoirradiated genome were made employing the lysismethod reported by K.M. Ulmer et al. (J. Bacteriol.138, 475, 1979). It could be shown that under allconditions tested 1.0 to 1.5 dsb in the DNA consti-tute a lethal event. In the presence of 0-.5 M EDTAunder air or nitrogen the first dsb is produced invivo with a dose about ten times higher than thedose required in the absence of EDTA. Since EDTA isa strong inhibitor of many enzymes, including nuclea-ses, it would appear that most dsb are made enzyma-tically, in accordance with the results for ssbfound by S.E. Bresler et al. (Int. J. Radiat. Biol.36, 289, 1979). The irradiation of calf thymus DNAin aqueous solutions in the presence of 10 Mcysteamine shows an approximately ten fold smalleryield of dsb as compared to that found in the DNA ofirradiated cells. The dose modifying factor (DMP) ofcysteamine on the survival of recombination deficientmutants was also measured. The DMF decreased from1.9 with AB 1157 (rec A ) to 1.0 with AB 2463(rec A 1,).

84

Modification of late postirradiation changes inelectrophoretic pattern of Bomirski hamster melano-ma (BHH) by irradiation conditionsK» Hyrc. K. CieszkaInstitute of Molecular Biology, Jagiellonian Univer-sity, Cracov, Poland

Populations of BHM cells are heterogenuous andconsist of "fast moving" and "slow moving" cellswhich have different electrophoretic mobilities(EPM). In tumours which developed from irradiatedcells the proportion of the "fast moving" cells isreduced* We studied the effect of hypoxia and hyper-thermia on the modification of EPM patterns causedby ionizing radiation. Cell cultures were irradiatedwith different doses of X rays under normal (air)and hypoxic conditions (nitrogen atmosphere) or ex-posed to 45.5 C. Irradiated and/or heated cells we-re injected into golden hamsters* The EPM patternswere examined of cell populations derived from tu-mours developed from irradiated or heated cells* Ir-radiation of primary cell cultures in nitrogen atmo-sphere reduced the "fast moving" cell fraction inthe developed tumour more effectively than irradia-tion with the same dose in air* Heating of primarycell cultures at 45»5 C (5.10,15 minutes) caused areduction of the amount of the "fast moving" cellfraction in the tumour by 50%*

Irradiation of cell heated at 45.5 C for 5 minu-tes did not change the reduction of the "fast movi-ng" cell fraction which had been caused by hyper-thermia treatment alone*

In contrast, the surface charge density, inferredfrom the mean EPM was modified by X-irradiation mo-re effectively than by hyperthermia*

85

THE EFFECT OF IONIZING EADIATION ON ELECTROPHORETICPROFILES OF MELANOMA CELLS GROWING IN VIVOK. HYRC. K. CIESZKAInstitute of Molecular Biology, JagiellonianUniversity, Cracov, Poland

Population of pigmented Bomiraki hamster melano-ma cells consist of two cell groups: "slow moving"cells and "fast moving" cells which have differentelectrophoretic mobilities (EPM). The aim of thepresent work is to study the electrophoretic patternof the cell population during tumour growth andchange caused by ionizing radiations of differentLET* EPM of melanoma cells obtained from tumoursof different size growing from n o n - i r r a d i -a t e d cells was measured as well as EPM of cellsderived from tumours which developed from i r r a -d i a t e d cells. Cell cultures were irradiatedwith different doses of fast neutrons (5.5 MeV) andX rays (250 kV) and injected into golden hamster.

Big tumours (V 1*5 car) contain about 60% ofthe "fast moving" cells. In tumours of the same si-ze which developed from irradiated cells the propor-tion of the "fast moving" cells is reduced. The re-duction is proportional to dose. The amount of the"fast moving" cells decreases to 33% for cells fromcultures irradiated with 4 Gy of X rays or neutrons.Froa these data we conclude that the appearance ofthe "fast moving" cells is related to cell differen-tiation and this process disturbed by ionizing ra-diation.

86

STUDIES ON THE ABILITY OF DIFFERENT FACTORS TO MODIFY THERADIOSENSITIVITY OF THE EARLY MAMMALIAN EMBRYOP. JACQUET and S. GRINFELD

Department of Radiobiology, S.C.K.-C.E.N.,B-24OO Mol, Belgium

The exact time of maximum radiosensitivity of the mouseembryo was determined by irradiating superovulated pregnantfemales each hour from the conception to the first cleavage andobserving embryonic development in culture. Radiosensitivityincreases from the conception to be highest 8 hours after pre-sumed superovulation, i.e. at the early pronuclear stage. Atthis time, LD50 for development to the blastocyst stage is 95rads, which contrast with the lower values found by othersafter _in vitro irradiation. For irradiation performed from 2 to9 hours after superovulation, important embryonic mortalityoccurs around the morula stage. When irradiation is deliveredfrom 5 to 12 hours after superovulation, a considerable letha-lity also occurs at the one-cell stage. The mechanisms of suchdifferential mortality are under study. j[n vitro irradiationsare also under way to control the possibility that maternalorganism could play a role in protecting partially the embryofrom adverse effects of radiations. On the other hand, when thepossibility of mating is restricted to 2 hours, i.a. from 3 to5 hours after presumed superovulation, we find an LD5O of about65 rads for the early pronuclear stage, a value somewhat lowerthan that of 95 rads which was found after caging the femaleswith the males for the whole night following hormonal (HCG)injection. The doses of hormones used to stimulate ovulationdo not modify the values of LD5O, which are also strictly com-parable to that obtained for embryos from mice naturally ovu-lated and mated in the same conditions. Results obtained todate strongly suggest that alcool consumption should not in-crease the radiosensitivity of the early embryo.

87

KEIATTCNSHIP BETWEEN SURFACE EXPOSURE DOSE AND EFFECTIVEDOSE EQUIVALENT

J.JRNKOWSKE, H.MIK0EAJEW5KA

Institute of Occupational Medicine, &5d£, Poland

Poland's system of individual dose monitoring of personsoccupationally exposed to ionizing radiation is based ondetermining the surface exposure dose registered on a filmbadge in a holder worn the laboratory coat at the chest'slevel. On the base of the reanmendations of the Interna-tional Octnnission of Kadiological Protection, the realionizing radiation is reflected, however, in the effectivedose equivalent . A question arises: does the effectivedose equivalent depend on the surface exposure dose regis-tered on the film badge and hew? Does radiation energy,distribution of surface exposure dose and direction of scat-tered radiation beam influence this dependence? Experimentshewed the relationship between the effective dose equiva-lent and the surface dose registered on the film badge.We observed the fluence of above specified factors on it.The effective dose equivalent (in renp anounts only to50% of the surface exposure dose (in R) registered on afilm badge at the chest's level of a person.

88

ESTIMATION OF LIFE-TIME DOSE IN PERSCNS EXPOSED OOCCJPA-•HONAELY TO X-RAYS

J.JANKOWSKI, P.SWIDERSKT

Institute of Occupational Medicine, LcSdi, Poland

In this report estimates are presented of the magnitudeof doses incurred over prolonged periods by individuals ex-posed occupationally to X-rays. Basis of the estimates wasformed by results of individual monitoring in Poland overthe period fran 1966 through 1978.

Probability distributions of receiving a given life-time(40 years) X-ray dose were deduced for several subgroups fromthe measurements by applying the method of Markov/s chains.Independently, by linear extrapolation of measured incrementrate, the mean life time doses were estimated (projected)for a number of subgroups.

The results seem to demonstrate that occupational expo-sure to X-rays in studied subgroups is little diversified andits current level is of the same order as that due backgroundradiation.

89

ADAPTIVE REPAIR OF E. COLI DAMAGED BY ALKYLATINGAGENTS

E. Janovska. 0. PillichInstitute of Biophysics. Czechoslovak Academy ofSciences, 612 65 Brno, CSSR

Adaptive response is an important error-freerepair process which protects various organismsfrom mutagenic and carcinogenic effects of smalldoses of alkylating agents. It was discoveredabout ten years ago and it manifests itself by alower lethal and mutagenic effectiveness of a givendose of the alkylating agent, if its applicationwas preceded by a low, adaptive dose. We have stu-died the kinetics of inactivation and the possibi-lity of repair of potentially lethal lesions, in-duced by the effect of methylmethanesulfonate(MMS), by means of this adaptive response in bac-terial strains of Eacherichia coli which were de-ficient in gene products involved in other DNA re-pair mechanisms. The results of our experimentshave shown that an inducible adaptive response ispositive in a parental strain and in excision re-pair defective mutants and so does not depend onthe products of the genes uvrA and uvrB. Since,however, the extent of the adaptive response inthe strain N630 carrying mutation in the recA geneis lower, it is obvious that an adaptive responserequires that there occur a certain recombinationof the damaged DNA. However, MMS-induced potential-ly lethal lesions are not repairable without theparticipation of DNA polymerase I: the extremesensitivity of the pol" mutants remained unchangedeven after the application of an adaptive dose ofthe alkylating agent.

90

LACK OF CORRELATION BETWEEN FORMATION OF SPLEEN CO-LONIES IN VIVO AND FORMATION OF GRANULOCYTE-MACRO-PHAGE COLONIES IN VITRO DURING POSTIRRADIATION RE-COVERY OF HEMOPOIESIS IN MICE HETEROZYGOUS AT STEELLOCUSD. JASKULSKI. C. SZCZYLIK. W.W.JEDRZEJCZAKDepartment or Immunology CKP WAM, 00-909 Warsaw

Mutations at Steel locus in heterozygous miceproduce no overt hematological abnormalities butimpair formation of 5-day endogenous spleen coloni-es and also increase radiosensitivity of affectedanimals. In order to investigate this problem ingreater detail groups of S1/+ and+/+ mice were irra-diated (3.5 Gy) and at daily intervals evaluated forthe presence of colonies on surfaces of their splee-ns. Moreover, at 2, 8 and 14 dqys postirradiationtheir bone marrow and spleen cells were cultured invitro in semisolid agar in the presence of colonystimulating factor in order to quantitate granulocy-te-macrophage progenitors (GM-CFU). It was foundthat at each time postirradiation S1/+ mice formedless spleen colonies than their +/+ littermate cont-rols and that these colonies reached confluency withdelay. In contrast to these findings marrow cellsfrom S1/+ mice formed significantly larger numbersof granulocyte-macrophage colonies in vitro thanmarrow cells from +/+ mice, while splenocytes for-med equivalent numbers of these colonies. These da-ta support the notion that Steel mutation variablyaffects different hemopoietic cells and preferenti-ally those that are capable of focal growth in vivo.

91

A SEARCH FOR GENETIC REGULATION OF POSTIRRADIATIONRECOVERY OF ERYTHROPOIESIS IN MICEWIESLAW WIETOR-JEDRZEJCZAK. ELZBIETA URBANOWSKADepartment of Immunology, CKF WAM, 00-909 Warsaw

Postirradiation (PI) recovery of erythropoieaisundergoea two phases: the 1st abortive rise (about4-10 day a PI) snd the 2nd: secondary rise (after 10days PI). This latter phase leads to final recovery.Following initial results showing that normal in-bred strains of mice may differ in magnitude of the-se two phases of endogenous postirradiation recoverythe reticulocyte frequency in the peripheral bloodhas been selected as the marker parameter of this re-covery. Groups of 10 mice (on one to 3 separate occa-sions depending on strain) were irradiated with 3.5Gy of X-rays and tested for 20 days afterwards at 2day intervals. It was found that in various strains (this recovery may follow one of the two alternative '<•patterns: with low abortive rise and high secondary \rise (L-H) and with high abortive rise and relative- Ily low secondary rise (H-L). The L-H pattern had theratio of reticulocyte count during the 2nd phase toreticulocyte count during the 1st phase above 2. TheH-L pattern had this ratio below 2. Poatirradiationbehaviour of reticulocyte count followed the L-H pa-ttern in C57B1/6, DBA/2 and Swiss:MIH mice, while inWB/R* and WC/Re it followed the H-L pattern. In AKR/ ./Cum mice this pattern was intermediate more close |to the H-L* Subsequently, F, and backcross (BC) micew«r« analyzed including B6AKF, CBD2F, WBB6F,, WC-SwissT, and WCSwissBC-, animals. Except for one inter-mediate situation the results obtained in these hyb-rid mice have shown that the H-L pattern was domina-nt and the L-H pattern was recessive. This may sug-gest that the pattern of PI erythropoietic recoveryin normal mice may be under control of limited num-ber (one or two) of genes.

92

125DOSES AND EFFECTS FROM I-TRIICDOTHYRCNINE INCELLS AND ORG^JISMSK.J. JOHANSON, S. SUNDELL-BERGMAN, AND H. CERDA.

Department of Radioecology, The Swedish Universityof Agricultural Sciences, P.O. Box 7031, S-750 07Uppsala , Sweden

Triiodothyronine (T3) binds to specific nuclearreceptors - a non-histone protein - which is boundto DNA. The number of receptors per cell varies froma few in the testis to about 6000 in the auteniorpituitary. There is also a variation of the numberwith age - in many tissues the number is higher inyoung age. Radioactive iodine is thus transported bynormal processes in the body to the critical part ofthe cells - in many tissues even to the mostradiosensitive cells.We have investigated the uptakeof I-T3 to various cells in vitro as well as invarious tissues in vivo. The number of

I-disintegration per cell was determined and theradiation dose to the cellular nucleus,in varioustissues was calculated.The effects of I-T3 oncells have been evaluated by studying accumulationof DNA-strand breaks, chromosomal damage and cellsurvival. The efficiency of I-T3-to induceDNA-strand breaks was similar to Iododeoxyuridinewhich is known to be very radiotoxic.

93

CHANGES IN REPAIR ABILITY OF CONTINUOUSLYIRRADIATED CELLSV. JurdSkovd, V. Dr6SilInstitute of Biophysics, Czechoslovak Academy ofSciences, Brno, fiSSRThe survival curves of LS/3L cells showed an expo-nential dose-response relationship without any shou-jIcier. The continuous irradiation in vivo of LS/BLcells at the exposure rate of 30 mGy.h" did notLead to any remarkable change of the D Q values, bufrom the 150th week of irradiation the initialshoulder appeared on the survival curve and its«ridth enlarged with the time of irradiation. Theextrapolation number (n) increased from 1.0 to 8.4after 350 weeks of exposure. The split-dose experi-ments (Elkind and Sutton, 1960, Hadiat.Res., 13,556) proved the reappearance of the initial shouldeifon the survival curves.

Cytogenetic analyses showed higher frequency ofstructural aberrations and SCEs in continuously ir-radiated cells.Our results gave the evidence that continuous irra-diation at low exposure rate lead to an increase inradioresistance of LS/BL cell population if suble-thal damage is involved.

94IN VIVO REPAIR OF POTENTIALLY LETHAL DAMAGE,LOTTE JULING-POHLIT INST. FUR BLOPHYSIKDER UNIVERSiTAT FRANKFURT.

Repair of potentially lethal damage (PLD) is wellknown to occur in in vitro cell cultures andkinetics of repair was measured(Pohlit, Hyder,1981,Radiat.Res.^7,613).For quantitative considerationsof in vivo systems/ such as tumours during radiationtherapy, it is necesarry to know if repair of PLDexists in vivo as well.Solid tumours of Ehrlich ascites cells were grownin the leg muscle of mice.To obtain a dose survival curve as known from invitro, the tumour of the mouse was irradiated invivo with 30 MeV electrons. For each dose one mousewas taken, and a single cell suspension was pre-pared by treating the tumour for 1 hour at 37°Cwith a dispase solution. This results in ashouldered dose survival curve, which agrees withthe in vitro one under hypoxia.In order to measure repair kinetics, tumours inmice were irradiated with the same absorbed doseand were treated with hypertonic dispase solutionafter different times of repair.Both results show that repair of potentially lethaldamage exists in vivo and is comparable to invitro findings.

95

CHROMOSOME RAOIOSENSITIVITY IN VARIOUS MAMMALIAN

SPECIES

I.KALINA? Gh.DEKNUPTb A.LEONARD1? H.KONECNA 8

a/Dept.Med.Biol.Fac.Med. .Safariks Univ.fco&ice,CS3R

b/Mammal.Genet.Lab.,Dept.Radiobiol.,Mol,Belgium

Venous blood samples from man, rabbit and pig we-

re exposed to O and 2 Gy of x-rays.Double cultures

of control and treated lymphocytes were incubated

in medium mitogen free for 0,1,2,3 hr in the pre-

sence ara-C( 5.10' M).Deoxycytidin 1., 1O~ M was ad-

ded to all cultures.After termination ara-C treat-

ments, PHA was added to all cultures as well as BidU

10 ug/ml to one each set cultures.

At 42 hr culture time in man all cells are in

their first cell cycle.In pig a few cells are all-

ready in their third cell cycle and in rabbit an

important proportion has reached third division.

Ara-C treatment increases considerably the unstab-

le chromosomal aberrations frequency in man and ra-

bbit but not in pig.The open lesion persist for at

least 3 hr in man,for 2 hr in rabbit jmd do not

reach 1 hr in pig.Consequently,the chromosomal abe-

rration frequency induced by 2 Gy following by ars-

C treatment is the highest in man,intermediate in

rabbit and anchangeid in pig.

96

ULTRASTRUCTURAL AND HISTOCHEMICAL CHANGES IN RATSAFTER SUPRALETHAL GAMMA-IRRADIATIONV.KAMARADDepartment of Histology end Embryology. MedicalFaculty, Palacky University, Olomouc, CSSR

The experiments were carried out with malerate exposed to whole body irradiation with 960 Gyusing a gamma emitter 6OC0 at dose rate of 1,1 Gy/sec. Brain, jejunum and testicles were studied. Therats died under the ray and the material was with-rawn immediately after the irradiation. Parietal lo-bes of the cerebral cortex showed pronounced chan-ges in all structures. Most neurons were dark. Pa-thological changes were characterized by a sharpincrease of electron density of the nucleus and thecytoplasm and accompanied by destructive changes inthe ultrastructure of basic organelles of the cells.Others neurons were with pronounced chromatolysla.Hietochemical investigation proved a strong reactionof acid phospatase in the cytoplasm of neurons,The-re were explicit disorders of the ultrastructurein glial colls. A marked ultrestructural injury ofthe endotheliun of brain capillaries, their basalmembrane and changes in the shape and size of thelumina of capillaries were demonstrated. In the wallof blood vessels a high activity of alkaline phospha-tass was found. In jejunum no pronounced changeswere observed. In some oolumnar cells ultrestructu-ral changes in brush border and mitochondria weredemonstrated. In epithelial cells higher activity ofacid phosphataee was found. In testicles we obser-ved only changes in ultrastructure of mitochondriaswelling and small number of cristae and dystrophicchanges in Setroli cells. The described changes ofthe brain capillaries we consider to be the primaryeffect of irradiation.

97

THE EFFECT OF 3H-THYMIDINE ON THE PROLIFERATION OF

IN VITRO CULTURED MAMMALIAN CELLS

3. Kaortova. E. MinaYovi

Institute of Biophysics, Czech. Acad. Sci., Brno,

Czechoslovakia

The effect of 3H-thymidine on the proliferation

of Chinese hanster cells (clons V79) was studied.

Following 3H-thyaidine application the prolifera-

tion of cells (studied on the basis of plating ef-

ficiency) was found to be diminished, the drop

being dependent on radioactivity ( 2 - 2 0 kBq/nl

cultivation aediua), the tiae of application

(2 - 20 h) and specific activity of 3H-thyaidine

added. Exogenous aacroaolecular ONA was able to

repair, to an important degree the radiotoxic ef-

fect of 3H-thyaidine on V79 cells by a aechanisa

other than the aere reduction of specific activity

of 3H-thyaidins.

98

EFFECT OF GAMMA IRRADIATION ADD COMPLEXES OF SOME3D-IONS WITH BIOACTIVE LIGAHDS OK BIOPHYSICALCHARACTERISTICS OF CELLS ADD CELL STRUCTURES OFMAMMALIAN BLOOD.P.A.EHAKIMOV. N.KH.SHADIEVA, A.B.AKBAROV, JU,N.IS-LAM07, M.K.PARMANOV, R.K.SIDDIKOV.Central Asian Medical Pediatric Institute, Tash-kent, USSR.

10 groups of rats irradiated with the dose of8 Gr of gamma-rays were investigated. They weredaily administrated by complexes with the doseof 5"lO~e6/e.

The object of investigation was peripheralblood. Electric properties of blood, its composi-tion, as well as DBA and RNA content were studiedby methods of bridge schemes, cell-fluoremetricand haematologic analysis. A + x+

Complexes containing Ccr , Ni and Cu asmetall-ions with vitamin "U" without Cl~ ionsand asparaginic (Asp-2H) or glutaminic (Glu)asidsas Uganda were tested.

In the ease of complexes containing Asp-2fi asa second ligand, coordinated by Cu* , significantincrease in intensity of secondary luminescenceof blood cells is observed, _ during transitionof Cor* complexes to those of Ml** with "U" vita-min.

Iti was shown, that the nature of biogenic 3d-ions exerted the substantial effect on studiedblood characteristics. In all cases the contentof Hi* ions in complexes as well as the presenseof Glu-ions instead of Asp-2H in them leads todecrease of electroconductivity and number ofleucocytes and to increase of that one of erythro-cytes.

99

EFFECT OP RADIATION AND MODIPICATORS OP RADIA-TION CASUALTIES ON ANIMALS CYCLASE SYSTEMKHALIKOV S.K., RABIffOVICH L.SH., MIRKHAMIDOVA P.Agricultural Institute, Tashkent, USSR.

Cyclase system is known to take an importantpart in message of hormonal effects and metabo-lism regulation. Intracellular cGMP contents al-terations in rat liver and spleen under the ef-fect of total f-radiation and injection of IJajaoxiana Eichwald, Yipera ursini renardi Ch, Vipe-ra lebertina turanica venom were studied by ra-dio immunologic method. Increase of cGMP contentsin 2, 24 and 72 hours after intraperitoneal in-jection of 1OO-5OO/tg/kg snake venom in liver anddecrease of cGMP level in 2 hours in spleen wereobtained. Then cGMP contents in spleen normaliz-ed. 800r radiation caused an elevation of oGMPconcentration in liver in 2 hours and decreaseof it in 24 and 72 hours. In spleen cGMF contentsdecreased already in 2 hours after radiation andthen these alterations deepened. Prophylactic in-traperitoneal injection of 150 and 500/*g/kg snakevenom 1 hour before 800r total radiation led tonormalization of intracellular cGMP contents inliver and spleen in observed time.

Basing on revealed results, we suppose, thatdecrease of cGMP levels in liver and spleen underradiation is connected with alterations of enzy-mes, taking part in cGMP metabolism. Injectionof snake venom as modificator of radiation casu-alties caused normalization of cGMP contents inorgans under radiation, that is why metabolismregulation was stabilised.

100

THE EFFECT OF SMALL DOSES OF IRRADIATION ON AFC

AND CAMP OF SPLEEN IN CHICKEN ONTOGENESIS.

KHAMIDOV D.Kh..NISHANBAEV K.N.,SHPOLJANSKY Ju.V.,POTAPOVA T.V.,ANDREEV A.V.

Institute of Biochemistry of Academy of Scien-ces of Uzbek SSR,Tashkent,USSR.

The spleen of 1-90 days old chicks,irradiatedbefore incubation in the dose of 0,029 Gr wasstudied.Cyclic AMP content in control group was1590+90,in experimental one-5040+102 pM/gr.Anti-body-forming cells(AFC) were seen in experimenttal and control groups on 11 day(725*5 and 22,4respectively).From 11 to 40 day cAMP and AFCcontents were increased in comparison with thecontrol.Since 40 till 50 day cAMP content wasdiscreased in experimental group(control-2190+90,exp.-1580+25 pM/gr).The amount of AFC wasdroped on 50 day(control-436,5,exp.-321,1).Sin-ce 50 till 90 day cAMP and AFC contents were in-creased in experimental group.Thus,on can sug-gest, that the small doses of irradiation stimu-late the differentiation of immunocompetentcells.

101

EFFECT OF PREINCUBATIVE IRRADIATION ON cAMPOF CHICKEN THYROID GLAND IN ONTOGENESIS

G.KHOJIAKHMEDOV.K.N.NISHANBAEV.D.KH.KHAMIDOV

Institute of Biochemistry of the Academy ofSciences of Uzbek SSR, Tashkent, USSR.

cAMP content in thyroid gland of 18 day

old embryos, 5 and 15 day old chicks hatched

from eggs, irradiated before incubation in

the dose of 0,029 Gr, was studied. It is es-

tablished, that cAMP of 18 day old embryos

is 2-fold increased in comparison with that

of intact ones. The difference between cAMP

content in thyroid gland of 5 day old intact

and irradiated chicks is minimized. 15 day

old chicks have shown the increase in intra-

cellular cAMP content in comparison with 5

day old ones; this increase was more prono-

unced in experimental samples.

Thas, one can suggest that the small do-

ses of irradiation affect the content of

cAMP-modulator in differentation and functi-

onal activity of the thyroid gland.

102

LET AH) RBE - I2SCNS FROM YEAST AND MMMRLIflNJTlrgen Kief erStrahlenzentrum der Justus-LIebig-UniversitStGiessen, Germany

The analysis of heavy Ion survival experiments shows thatneither diplold yeast nor Chinese hamster cells are killed bythe passage of a single particle through the cell nucleus.It is, therefore, suggested that the reduction of relativebiological effectiveness (RBE) with high linear energy trans-fer (LET) is due to saturation at the molecular level ("mole-cular overkill") rather then to "cellular overkill". The for-mation of initial lesions depends on the energy depositiondensity in nananeter sites. Their yield: increases with IETup to about 500 KeV/mn beyond which saturation occurs. Lesionsmay be repaired/ the probability for, this to happen nay be afunction of their initial proximity. It appears that there isan important difference between microorganisms and mammaliancells: yhile repairability is largely unaffected by the spa-tial distribution of initial lesions in the former, it Issignificantly reduced in the latter by a close proximity.These considerations are substantiated by a quantitativeanalysis of survival and mutation induction in yeast andmammalian cells exposed to heavy ions.

103

EFFECTS OF UV-IRHADIATION 00 THE CELL CYCLEIN CHINESE HAMSTER CELLS WITH DIFFEBEOTUV-SEHSITIVTTYT.V.KiaiLLOVA and YU.M.ROSANOVInstitute of Cytology Aoad.Sol.USSR, Leningrad,USSR*

Analysis of the distribution of oells throughth« phases of ths osll oyole by DHA flow oyto-fluoriaetry has btsn utilised to investigate theeffeets of DV-irradiation on cell oyele progres-sion in asynohronoas ohinese hamster oells withdifferent UV-sensitivity, UV-resistant V79 oellsand UV-sensitive olones Br, CHS1, 0H82 and ZZIwere studied in tlme-aourse and stathnokinetieexperiments* UV-irradiated oultures show a largeaoouantlation of oells in S phase % the effeotlnoreases with UV dose froei 1 to 10 J» • UV-sen-sitive olones show a larger and store prolongedinorease in the proportion of oells in S phaseafter Irradiation in less doses than UV-resistantoells* Besides UV-sensltlve clones show an inhibi-tion of sioveBent of irradiated oells from 0- into8 phase} 5 Jm W oauses O^blook for 6h and 15hin CHS2 and XII elonea respectively• The dataobtained point to an Inhibition of initiation anda larger inhibition of elongation of DHA eyntheelsin W-seneitlve olones after UV. Che resultsioggest a oorrelation with UV-eell sensitivity duete the survival criteria*

104

LONG-TERM FOLLOW-UP AFTER ACCIDENTAL GAMMAIRRADIATION FROM A Co-60 SOURCE

R.TUSCANY, J.VEJLUPKOVl, J.DVO&CK,

Institute of Hygiene and Epidemiology, Prague,CSSRClinics of Occupational Diseases, Faculty ofMedioine, Charles University, PragueDepartment of Ophtalmology, Policlinics of theFaculty ot Ifedioiae, Chari.es University, PragueChirana, xue*, Prague

In December 1973 a technician was accidentallyirradiated when attempting to bring under controla sealed Co-60 source (110 TBq) which had beenblocked in the head of a medical irradiation unitduring a refilling operation. In the early periodafter the accident severe skin changes on the lefthand, epilatlon ot a small area in the left tempor-al region aad minor deviations in peripheral blooddeveloped* In the following years repeated surgerydue to secondary skin defects of the left handresulted la the loss of the II-V fingers* Since1975 changes in the leas of the left eye began toappear leading gradually to the deterioration ofthe visas* later the opaoltiea of the lens of theright eye were found* Cytogeaetie studies contri-buted in the early period to the dose evaluationand to the judgement on the health Impact of theaccident* The equivalent of the whole body dosewas assessed as 1*4 Gy* The oytogenetio analysisla the course of following years showed the pat-tern ot clearance of aberrant lymphocytes from theperipheral blood* Transient appearaaee ef oloaalsubpopulatleas of aberrant cells has been observed*

105PROTECTIVE EFFECT OP CYSTAPHOS (WB-638) IN SEMI-LETHALLY IRRADIATED GOATSR. Kljjajjid, Z* Milosevic, Emilija HorsicDepartment of Radiology of Veterinary Faculty71ooo Sarajevo, Yugoslavia

The preparation was applicated intramuscularly inthe dose of lf?6 mg/kg 3° minutes before irradiationon linear accelerator with the dose of 2*4 Gy.

The animals were observed in the course of 3odays while efficacy of the protector was determinedin relation to the time of survival, clinical pict-ure, hematological and bio-dosimetric status andpathomorphological changes*

Results indicated that cystaphos had a good pro-tective effect on hemopoietic system in semilethallyirradiated animals while the protective effect ingastrointestinal system was poorly expressed*

106

THE INFLUENCE OP HYPOXIC CONDITIONS ON THE

IMMUNOLOGIC REACTION AND PHAGOCYTIC ACTIVITY

OF BLOOD CELLS AFTER WHOLE BODY IRRADIATION

OF SWINE WITH 2,0 Gy

F, KOCH, F. KAMPRAD, I. BUCHHOLZ

Karl-Marx-University, Leipzig, GDR

Swine at age of 3 month were exposed to Co-gammawhole body irradiation with moderately lethal dose(LDpo/™) °f 2,0 Gy* 9 animals being exposed inrespiratory hypoxia to 10% Op and 6 animals beingexposed to normal 21% 0~ content. 6 animals weresham irradiated. Active immunization with humangamma globulin 2h and 32d after irradiation wasused as test model. For determination of the pha-gocytic activity of blood cells 0,2 ml blood wasincubated with a bacterial suspension and C-glucose. The decarboxilation rate was measured.The antibody reaction after primary and secondaryantigen application was significantly decreasedin the two groups of irradiated animals. In thehypoxic group a slowly decrease of the antibodytiters in relation to the control group was ob-tained. But the difference between the irradia-ted groups is not significant. By contrast withthe markedly decrease of neutrophiles in the peri-pheral blood the phagocytic activity of bloodcells was only little diminished. In tendencya protective effect of hypoxy was observed in thethird and fourth week after radiation when thenumber of neutrophiles are very low.

107

LATE EPPECTS OP RADIUM AND PLUTONIUM IN MICEY.gQFRANEK. V.SVOBODA-, A.SEDLAK, V.DVOftAK*Institute of Hygiene and Epidemiology, Centre ofRadiation Hygiene; xliedical Faculty of Hygiene,Charles University,Prague, CSSR.

The long-term experiments were performed usingfemale ICR/SPF/ mice aged 10 weeks. While 226Ra andz^"Pu were given in ai single intravenous or intra-peritoneal injection, the activities of 224Ra wereinjected in one hundred and fifty fractions. Theanimals were kept under standard conditions and mo-nitored daily until extinction. They were examinedroentgenoftraphically and histopathologically withspecial respect to the diagnosis of osteogenic sar-comas. In the case that the average cumulative ske-letal doses after injection of 224Ra and 239Pu weresimilar, the incidence of osteogenic sarcomas wascomparable. This means that in both cases of conta-mination the risk of osteosarcoma induction couldbe practically of the same degree. It was estima-ted that after incorporation of 224-Ra and 239Puand under condition of comparable average skeletaldoses the bone sarcoma induction probability-wasten times higher them, in the case of 226Ra. Withregard to the cumulative incidence of hemoblasto-ses, evaluated one year after administration of ra-dionuclides, it was related to the activities in-jected. In comparison to the controls, the occur-rence of hemoblasti.c malignancies was shifted tothe younger age and I the survival of animals was ap-parently shortened..

108

EFFECT OF TESTOSTERONE ON SYNTHESIS OF NUCLEIC *ACIDS IN GERM CELLS OF IRRADIATED ANIMALS

V.G.Kondr.atenko, L.F.Ganzenko

Institute of Biological Physics, USSR Academy ofSciences, Moscow, USSR

The disturbance .of spermatogenesis observed af-ter irradiation of animals is caused in general bychanges of synthesis in spermatogonia of differenttypes and spermatocytes-1 in populations.

We have studied the changes of DNA and RNA syn-thesis in germ cells of 76 mature white mice malesafter total-body ^-irradiation with the doses of2 and 4 Gy and testosterone injections. For thispurpose we counted the number of spermatogonia A..-4, In, B and preleptotene and pachytene spermato-cytes labeled with 3H-thymidine and 3H-uridine atI-VIII stages of spermatogenous epithelium. The num-ber of synthesizing cells decreases 3 times afterirradiation of animals. Testosterone-propinate in-jected an hour after the irradiation caused an in-crease of synthesizing cells number. The number of3H-thymidine-labeled spermatogonia increased 15 and20 per cent after the irradiation with the dose of2 Gy and 5 and 15 per cent with the dose of 4 Gy./She number of labeled preleptotene spermatocytesincreased 10 per cent. The number of 3H-uridine-labeled cells increased 10 and 20 per cent after ir-radiation with the dose of 2 Gy and 8 and 10 percent with 4 Gy.

Thus, the modification of germ cells reaction toirradiation is caused by testosterone influence onnucleic acids synthesis in these cells. These re-sults are important for modification of spermatoge-nesis pathological reactions after the influence ofdifferent environmental factors.

109DIFFERENTIAL MODIFICATION OF SUBCELLULAR RADIOSENSITIVITYA.H.T. KONINGSDept. of Radiopathology, Bloemsingel 1, 9713 BZ Groningen,The Netherlands

Radiation-induced! reproductive death is probably caused by in-effective repair of DNA damage. From experiments with erythro-cytes (Konings 1981 Int. J. Radiat. Biol. 40, 441) we know thatmembrane damage (Hb loss) can already be defected after verylow doses/dose rats of X-rays. By changing liptd compositionand antioxidant status of model membranes (liposomes), radiat-ion damage can be modified (Konings et al. 1979 Int. J. Radiat.Biol. 35, 343).In the experiment to be discussed, membranes of mouse fibro-blasts have been altered and the antioxidant status (GSH,u-tocopherol) has been changed. Clonogenic ability (DNA) andpotassium loss (membrane) has been investigated in the samebatch of cells after different doses of X-irradiation. Changesin the amount of polyunsaturated fatty acids in the membraneand alterations in GSH and a-tocopherol content have clearconsequences for K+ loss over the membrane (high doses) but notfor clonogenic ability (lower doses).These experiments indicate that different targets (DNA, mem-brane) within one^celi may react differently in terms of sub-cellular radiosensitivity after modification of cellular GSHand a-tocopherol.

IK)

H'fPEHTHBHMIC RADIOSENSITIZATIOIJ A1ID HYPERTHEHKICKILLING IK MAMKALIAN CELLSA.G.KOHOPLYANNIKOVResearch Institute of Medical Badiology, O-fcninsk,USSR

The actiotf of hyperthermia and gamma-$i&ysapplied separatly and in combination to severalexperimental models - mouse leukemic cells (strainLa); stromal colony-forming units (CFU-F) of ratbone marrow; colony-forming units (CFU-S) of micebone marrow ; solid and ascites tumors, of mice andrats (Ehrlich ascites carcinoma, Lewis lung carci-noma, rhabdoniiosarcoma R1, sarcoma T1) was studied.Cells and tissues of mice and rats were heated ina water bath or with highfrequency microwaveradiation. oOco gamma-irradiation was carried outat a dose rate of about 1 Gy/min.

The "heat-survival" curves for mouse leukemiccells in a temperature range from 40 to 45°C wereshown to be exponential. The gradual increase 'oftemperature by 1°C in the range mentioned resultedin a similar decrease o*f Do. The investigation ofCFU-S heat inactivation showed a similar picture.However, in this case the "heat-aurvival" curvesfor 41-42°C had a "shoulder". Leukemic cells were5-7-fold more sensitive to heat treatments comparedto their normal equivalents CFU-S.,•

Heating treatment of normal aftd tumor hemopoieticcells prior to gamma-irradiation decreased Do. WhenEhrlich ascited carcinoma ce&lls and Lev/is lungcarcinoma cells were heated in vitro the resultswere similar to those obtained for normal andleukemic hemopoietic cells. Normal &nd tumor cellsexposed to heat and ethanol revealed induce thermo-tolerance. The radiosensitizing effect of hyper-thermia on the slowly growing rat tumor R1 wasgreater than on the fast growing tumor T1.

Ill

THE EFFECTS OF PROTEINASES, THEIR INHIBITORS AND INTERFERONSON REPAIR GF RADIATION-INDUCED POTENTIALLY LETHAL DAMAGE

M. Korbelik(1), J. 3krk ( 2\ A. Suhar(3), P. Schauer(i|)

D. Petrovic(1) and V. Turk^3)

(1) R. Boskovic Institute,'Zagreb; (2) Institute of Oncology,Ljubljana; (3) J. Stefan Institute, Ljubljana; (4) Instituteof Microbiology, Ljubljana, Yugoslavia

Expression and repair of potentially lethal damage (PLD)seems to be linked to proliferative status of the cell andprogression in the cell cycle. Some intracellular proteinasesare engaged in the regulation of molecular events by which acell progresses through the cell cycle, and also in inductionof cell growth in quiescent non-dividing populations. Inter-ferons alpha, beta and gamma have ... A shown to affect intra-cellular. proteinases activities.In this work, the effects of intracv. jLular and extracellularproteinases and their inhibitors, and also of interferons, onthe repair of PLD induced by gamma radiation was examined.Chinese hamster V79 cells were grown to confluence and kept5 days in plateau-phase before thay were irradiated at 0 C.Immediately thereafter agents under study were added to thecultures and left throughout the PLD, repair interval at 37 C.The increase in survival due to PLD repair was stimulated bysome agents (e.g. neutral serine proteinase, interferons alphaand gamma) and inhibited by some o'thers (including leupftptinand interferon beta).

112

THE OXYGEN EFFECT IN BACTERIOPHAGE IRRADIATED INDIFFERENT MEDIA

Ju.N.Korystov, F.B.Vexler

Institute of Biological Physics, Academy of Sciencesof USSR, Pushchino

The oxygen effect (OE) on radiation inactivationof phage T4 in a salt solution and bactopeptone wasstudied. It is shown that the sign and magnitude ofOE depend on media and the conditions of the post-irradiation incubation of the phage. In salt solu-tion was observed the direct OE. The direct OS isdue to postirradiation lesion of the phage by hyd-rogen peroxide (H0O2) which is formed in greateramounts upon irradiation in oxygen than in anoxia.The addition of catalase is shown to eliminate thepostirradiation inactivation of the phage. In thiscase an opposite OE is observed as a result of ascavenge of hydrogen atoms which damage the phage byoxygen. It was shown, that the irradiation of thephage in concentrated bactopeptone^ >O.QZ°fo resultedin an oposite OE which was due to a greater damag-ing effeciency of S* as compared to that of oxidizedradicals of bactopeptone (BO2). We have evaluated acontribution of the indirect effect on the irradia-tion to the damage of the phage under various condi-tions. This allowed us to compare the efficiency of6' (0.46)andB02(0.16jwith respect to *0H. The

dose curves were shifted from the exponential cha-racter when the phage was irradiated in 0.005-0.01^bactopeptone. This shift can be explained by the de-crease of bactopeptone molar concentration resultingfrom recombination of the radicals of bactopeptone.Under irradiation in oxygen postirradiation actionof hydrogen peroxide was shown to contribute to theshift aforsaid as well.

113

THE EFFECT OF GAMMA IRRADIATION ON THE PHOSPHA-TIDYLCHOIINE MEMBRANES

M. KOTER , M. BRYSZEWSKA

Department of Biophysics, University of Lodz,Lodz, Poland.

The effect of gamma irradiation on the stru-cture of model membranes prepared from egg yolkphosphatidylcholine was followed by electronspin resonance. The membrane suspensions wereirradiated with a dose rate amounting to 1 0kGy h in the range 0.5-6x10^ G. Multilamellarliposomes were spin labeled by TEMPO and 5-do~xylpalmitate acid methyl ester.The spectral parameter of TEMPO decreased 4

with the increasing dose /about 30% for 4x104Gy/. It means that the amount of the spin la-bel in the lipid phase diminished. After irra-diation of phosphatidylcholine membranes anincrease of the correlation time of liposomeslabeled with 5 doxylpalmitic acid methyl esterwas observed /about 10% for 4x104 Gy/. Thisindicates that immobilization of nitroxide gro-ups occurs and, therefore, the membrane micro-viscosity in the regions investigated is incre-ased. The results obtained may suggest thatthe disorganization of the polar regions ofmembranes induced by gamma irradiation exists.

1 1 4

ORGANICALLY BOUND TRITIUM IN THE MAJOR BRAIN PHOSPHO-LIPIDS OF RATS LIFETIME EXPOSED TO TRITIATED WATERAtfD TRITIATED FOOD

M.KCWALSKACenfral'Kboratory for Radiological Protection,Warsaw,Poland.

Organically bound tritium was determined in fivemajor phospholipids (e.g.phosphatidylcholine,phospha-tidylethanolamine,phosphatidylserine,phosphatidylino-si tol and sphingorayetin) separated by thin-layer chri>-matography from an organic phase of whole brain ex-tract of 21- and 120-day-old rats,lifetime exposedto tritiated water(37.0 KBq/ml) and tritiated food(48.1 KBq/g). For all studied phospholipids tritiumincorporation from tritiated food was significantlyhigher than incorporation from tritiated water. Thehighets specific activity of organically bound trit-ium was found in phosphatidylcholine and the lowestin phosphatidylinositol. The highest tritium incorpo-ration was observed in 21-day-old rats,weaned frommothers who had received tritiated water and tritia-ted food during pregnancy and lactation.

These results suggest,that organically boundtritium in constituents of maternal milk was utilizedto a greater extent for synthesis of brain phospho-lipids than organically bound tritium from tritiatedconstituents of food arid tritium from tritiated vater.

115

THE BOLE OF DNA REPAIR IN REALISATION OF OXYGEN

EFFECT IN DIFFERENT MUTANTS OF ESCHERICHIA COLI

S. KOZUBEK. E.A. KRASAVIN, K.G.. AMIRTAYEV

Joint Institute for Nuclear Research, Dubnes USSR.

We propose a new model reflecting oxygen effect

realisation in E.coli cells. Thie simplified assumpt

ions are: 1.Two types of DNA injuries: modifiable

(MQ) end unmodifiable (MN) by oxygen. 2.Two systems

of DNA repair: F-fest (polA dependent), S-slow (rec

-lex dependent(. 3.Some small pa:rt of DNA injuries

cannot be repaired by F-system; V.hese injuries are

preferably of M^ type (e.g. multiply damaged sites).

The model explains that: 1.The block of slow repair

leads to increased sensitivity and decreased oxygen

enhancement ratio (OER). 2.The block of fast repair

leads to increased sensitivity encl increased OER.

It explains the sensitivities and OERs in the case

of rec" and polA" mutants. The model predicts that

the OER of polA" strain should reflLect the OER of

the initiel DNA injuries. Actually both OERs are

4-5. The production of F-irrepairefc'le injuries was

estimated to 10 ^cGy dalton . Some predictions of

the model has been tested in our experiments andgood agreement has been achieved.

116

;•. CUÊCTlCi; C7 TKL KSII CCkCEPTICh USI/)

£-. KlZUhrK. P. VCDV/ŘKA

ccint Institute fcr ivuclear Research, Lubnn, USSR.

hřčiother* peuticrl Department of üstrava Medical

Centre, Paskov, Czechoslovakia.

tn the basis cf earlier investigations (Kczubek,19£2

Int.c .h^diEt.Cncol .üicl.Phys. ,£, 1 #75, Kozubek, Vodvář"

kf-, 1S64, .\ecplf:smr- JJ_,2C3) the validity of NSD cen

be considered. \SL gives feirly gccd predictions cf

' tolerance doses fcr dsily frectior.rticn. Cther sche-

! mes of frncticnetion require corrections cf KSD. In-

stead of usually used TLF=1 0" 3.N.d 1' 5 3 8.t" C # 1 6 S ; (re-

number of fractions, d-dose per fraction, t-time bet

ween fractions), we propose simpler but more precise

quentity JJFT^.d1 #6<7 for lp.te reactions end DFT=N.

(d+1 .2) 1 <fc7-/?o(T-To) for acute reactions (d>1 .23 Gy,

T>T ), where /3 is the rste cf repopulstion, T is

the deley cf repopuletion (/3=3, T =2C in Gv.dey for

human skin). Volume dependences cen be introduced by

the ssme w?y ss in NSD,, According to the new epproech

conventional frectionetion in rediation therapy of

cancer is reasonable. Currently proposed hyperfrac-

tibnetion is net experiraentelly substsntifted. Other

changes cf NSD (e.g. LQ model) are net necessary.

117

THE EFFECT OF /#-(l—»3)-D-GLUCAN ON HEMOPOIETICRECOVERY IN LETHALLY IRRADIATED AND BONE MARROWTRANSPLANTED MICE

A. Kozubik. M. Pospisil, D. Netikova, D.

Institute of Biophysics, Czech, Acad, Sci.,Brno,CSSRx T'Institute of Chemical Technology, Prague

The experiments were aimed at studying thetransplantation efficiency of pluripotent hemopoie-tic bone marrow cells in the conditions of activa-tion of the macrophage system. Use was made of thespleen colony method (including also the retrans-plantation alternative) and further of the methodof incorporation of I25i-iododeoxyuridine intothe DNA-synthesizing cells as an indicator of pro-liferation activity. Mice of the strain C57BL/10were injected 24 h prior to irradiation withparticipate j&-(I—j5)-D-glucan at a dose of 2 mg.The animals were gamma irradiated with lethal do-ses; suspensions of bone marrow cells from intactdonors were i.v, injected within 2 h after irra-diation* The glucan-affected environment of thetransplantate recipients was found to potentiateproliferative processes in the spleen and femoralbone narrow. Simultaneously, demonstration waaprovided for the capability of glucan to enhancethe survival of CPUs in the irradiated organism.

118

RECENT ASPECTS IN THE PATHOPHYSIOLOGY OF RADIATIONINJURY

G.J. KQTELES

"Frederic Joliot-Curie" National Research Institutefor Radiobiology and Radiohygiene, H-1775, Budapest,POB.101. Hungary

Due to the complex nature of radiation-induced alte-rations of cells, tissues, organs and organisms, thepresent review has to be restricted to certain cellu-lar and tissue reactions which might contribute tothe development of radiation injuries. At cellularlevel even non-lethal doses result in temporary"disabled conditions" through alterations of membranesystem being either the only target or a cooperativeone. Changes of specified regions of membranes influ-ence their reactions like polarity of surface charges,cell-to-cell contacts, and functional units likereceptors. Microdosimetric explanation is emerging ifprojection of extent of single or a few energy depo-sition events is made over biological structures rep-resenting various cell functions on micro- or nano-meter scales. Consequently, subcellular lesions likethose of membranes may include structural rearrange-ments, functional disturbances, metabolic disorders,differing replacements of damaged biomolecules.Tissue organization by cells of various radiosensiti-vities and their contacts with each other as well aswith extracellular matrix has a decisive role inpathophysiology of radiation injury. Identificationsof most sensitive sites and targets, their possibleprotection is crucial in prevention of non-stochasticeffects, e.g. those caused by vascular degeneration.Insight, into these pathophysiological processes includ-ing interactions in combined /thermal burn, multipletrauma/ injuries aims also diagnostic and therapeuticapproaches.

119

HEAVY ION INDUCED DOUBLE ANDSINGLE STRAND BREAKS IN SV40 DNA

G. Kraft*, R. Roots**

GSI Darmstadt, LBL Berkeley

The influence of the radiation quality on the biological responsehas been studied on different biological levels like reproductivecell death chromosomal aberrations1 and DNA damage of mammali-an cells2 In all these experiments, a similar trend is observed:For the very heavy particles, the optimal efficiency does notcorrespond to the highest values of the linear energy transfer(LET) which occur for the heavy particles at about 2 MeV/u.With increasing track diameter, an increase in the biological effi-ciency is observed, even if the LET decreases. Therefore, thesuggestion of a basic physical process was made3 which governsthe radiation response and which can be also demonstrated at theradiation response of a biological macromolecule like DNA. In theexperiment SV40 DNA was exposed to particle beams from heliumto uranium in the energy range between some MeV/u to approx.1 GeV/u at the Unilac, Darmstadt and Bevalac, Berkeley. Fromthe dose effect curves, the cross sections for the induction ofSSB and DSB were calculated separately. The o-LET depend-ence of the induction of SSB shows a remarkable agreement in itsgeneral pattern with the inactivation cross section given inref.3. Therefore, we assume that the postulated saturation pro-cess in a consequence of early physical processes like recombina-tion effects in the particle track rather than a biologicalsaturation effect (overkill).1 W. Muller et al. this report2 E. Aufderheide et at., this report3 G. Kraft et a l . : HZE effects on mammalian cells to be

published in Advances in Space Research.

120

MECHANISMS CF THE BIOLOGICAL EFFECT OF DIFFERENT

IONIZING RADIATIONS.

E.A.KRASAVIK. S.K0ZU3EK

Joint Institute for Nuclear hesesrch, Dubna, USSR.

Theoretical end experimentsi investigation of the

role of DNA repair in biological effectiveness of

ionizing rscir-ticn with different LET wss done for

pro- end eukeryctes. It is suggested thet low-LET

rsdisticn leeds mainly to enzymatic double strend

bres-ks (LSB). Their number cen be influenced by many

fr-ctors of biologicel nature. High-LET particles

produce direct DSB. Their number depends on physical

characteristics of the redietion. A number of expe-

rimental results in favor of this hypothesis were

obtained on E.coli wild type cells end isogenic mu-

tents (rec~, pclA~, Gfmmr), yeest cells Sschprorayces

cerevisie &nd its mutsnts (red 6), end Chinese hsm-

ster cells in the presence fnd absence cf Cytosine

rrrbincsid. The differences in the sensitivities

cuickly diminish while LET increases. A biophysical

model has been developed explaining the fects on

considering both biologice-1 factors such as repair

systems and physical cherecteristics cf redietion

such as track structure end energy fluctuations in

sensitive cell structures.

121

RESTRICTION ANALYSIS OF rDNA FROM GIANT CELLS (SACCHA-ROMYCES UVARUM) GROWNAFTER X-IRRADIATIONKREISS, M., BAUMSTARK-KHAN, C , RINK, H.Institute of Radiation Biology,Bonn, Federal Republic of Germany

Diploid yeast cells (S. uvarum) irradiated with X-rays (1 kGy,1% survival) and grown in liquid media form giant cells. Thetotal rRNA content in these cells is decreased, although dis-tinct rRNA species respond in different ways. The effect of io-nizing radiation on rDNA was studied by restriction analysis.

Ribosomal DNA in Saccharomyces accounts for about 10-12% of thetotal nuclear DNA. The 100-140 copies per haploid genome codingfor ribosomal RNA are arranged in tandem repetitive clusters.Each tandem unit consists of a gene encoding the 37S.precursorrRNA, a 5S rRNA gene and a non-transcribed spacer.

rDNA was isolated by isopycnic banding in CsCl-gradients con-taining the fluorescent dye Hoechst 33258. Isolated rDNA fromgiant cells (grown 24 h after irradiation) was digested withrestriction enzymes Sma I and Eco RI respectively and comparedto the restriction pattern of rDNA from unirradiated cells.

With irradiated as well as with unirradiated yeast cells diges-tion of the rDNA with Sma I yields one fragment, representing amonomer unit of the repetitive rDNA, digestion with Eco RIyields 7 fragments.

A lack of differences in restriction patterns might be due torepair processes during the culture period. Further experimentsimmetiately after irradiation are in progress.

122

POSSIBILITIES OF MODIFICATION OF LATENT RADIATIONINJURY IN RAT LIVER BY RADIOPROTECTIVE AGENTSK. KROfXSOVA. E. MlSlJROVX. E. MlSUROViS

iol. UPJS, CSDept. Gen. Biol. UPJS, CSSR

Changes in mitotic index, metaphase to prophaaeratio and frequency of chromosomal abnormalities,induced in rat liver by whole body X-ray irradiati-on with the dose 5.74 Gy, were studied during 14day regeneration after partial hepatectomy.

The study was focused to modification of the ra-diation effect with radioprotective substances -cysteamine and adeturon. Basing on changes in mito-tic index and metaphase to prophase ratio in rege-nerating liver, mechanisms participating in celldivision are supposed to be disturbed in intact li-ver already during irradiation.

On the other hand, decreased frequency of chro-mosomal abnormalities, even with postirradiationapplication of cysteamine or adeturon, demonstratesthat the development of latent, radiation inducedinjury of genetic material continues also after ir-radiation and may, in part, be affected by the ra-dioprotective agents applied in short postirradia-tion period.

123

LECTIN-BINDING BY BLOOD CELLS OF RADIOTHERAPVPATIENTS AND DOSE ASSESSMENTS

Tamara KUBASOVA, G.J. KO"TELES, L.idi a SIMBIRTZEVA+,V.F. MUS+, E.A. ZHERBIN+, K.P. HANSON+, I. SINKOVICSH-Zs. KARIKA++

"Frederic Jolio-t—Curie" National Research Institute forRadiobiology and Radiohygiene, H-1775. Budapest,POB.1O1. Hungary, Central Research Institute ofRoentgenology and Radiology, Leningrade, USSR,++National institute of Oncology, Budapest, Hungarv

Radiation-induced alterations of H-convanavalin Abinding capacities of blood cells were suggested aspossible biological indicators of radiation injury"/Kubasova et al. ,1981,Int. J.Radiat.Biol. ,40,187-194/.An approach to test the applicability of this tech-ninue in irradiated human organisms 18 natients withvarious solid tumours and 7 persons with lympho-granulomatosis were examined. Blood samples wereobtained before and 1,4,24 hours after radiationtreatment. Separations of platelets, lymphocytes anderythrocytes were performed in one step bv Ficoll-Uromiro gradients. The binding of 3n-conA to variouscell types of different radiosensitivities indicatedthe dose-range received by the patients between 0,5and 2,2 Gy partial body irradiations. The assessmentsof doses by this biological technique proved to be ingood agreement with the doses determined by nhvsicalmethods in 78 per cent of solid tumor cases, andapproximate values were obtained for the rest ofsolid tumor bearing patients and for those withlymphogranulomatosis.

124

COMPARISON OF TOXIC AND RADIOPROTECTIVE EFFECTS OPCYSTAMINE WITH GAMMAPHOS (WR-2721)KUNA P.Purkyne Medical Research Institute, Hradec KTalove*,CSSR

Acute toxicity of i.p. or i.m. administered WR--2721 was 2.5 - 3.2 times lower than cystamine,when lethal doses of protectors in mmol.kg(LDf-a/.p h) served as criterion of toxic effectsin mlfct? The LD 50/48 h of i.v, injected WR-2721was determined on 6.2 mmol.kg, the level of to-xic doae,of i.v. administered cystamine was 1*0mmol.kg .

Cystamine, administered i.p. or i,m. in the do-ses which represent 40-60 % of its toxic dose(LD 50/46 h), protected mice against lethal effectof whole body gamma irradiation with DRF 1.4-1*8.Similar protective effects were estimated afterinjection of 10-20 % of toxic dose of WR-2721.WR-2721 administered in the range of 30-40 % ofits toxic dose increased radioresistance of micewith high values of DRF 2.1-2.7.

Our results indicate, that WR-2721 is moreperspective radioprotector than cystamine.

125

NEW ASPECTS OF MOLECULAR MECHANISMS OP ACTIONOP NITROCOMPOUND RADIOSENSITIZERSZ.V.KUROPTEVA, M.K.PULATOVAInstitute of Chemical Physics of the Academy ofSciences of the USSR, Moscow, USSR.The EPR method was used to study the transfor-

mation and cell action targets for the number ofnitrofurans and nitroimidazoles in the animal or-ganisms. The compounds were injected intraperito-neally after that animals were killed in definitetime intervals, the liver and blood were extractedand the EPR spectra were recorded at 77 K.

Earlier it was known that the nitrofurans andnitroimidazoles are reduced in mammalian tissuehomogenates. The nitrocompounds were shown by usto decompose after reduction to yield nitric oxi-de. Nitric oxide formed in the organism is accep-ted by iron containing cell proteins to providenitrosyl complexes of hemoproteins (heme-NO) andironsulfer centers (ISC-NO;. The appearance of thenitrosyl complexes is an evidence for a develop-ment of the hypoxic state in the tissues and orga-nism. This state is temporary and its durationdepends on the compound kind. The SPR spectra ofnitrosyl complexes detected in the blood and liverdisappeared 1.5 - 2 hours after injection. Inaddition the nitrocompound. injection also resultedin a considerable increase of ubisemiquinone sig-nal in the liver EFR spectra, which indicates in-hibition of mitochondrial electron transfer chain.It was established that the extent and duration ofthis inhibition is dependent on the chemical natu-re of the compounds. A definite correlation bet-ween the extent of respiratory chain Inhibitionand th» radiosensitizing capability of the nitro-oompounds studied was found.

126IMPACT 1 3 7Cs TO LIMITING LAKEJ. KWAPULINSKI1, J. SAROSIEK2

1. Department Toxicology University of MedicineK-ce

2. Institute Botany University of Wroclaw, Poland

The fission product concentration in water, se-diment and plant have been used to estimate dosecommitments. Samples of water, sediment and planthave be«9»collected from 9 points of lake. Determi-nation J Cs content were carried-out by method6 - radiometric after radiochemic analysis, withexperimental accuracy fbout -15%. It was estimatedremoval half-times of J/Cs from water which itfasted from 5 to 20 years. The distribution ofJ7Cs in typical sediment core with depth and in-

fluence hydrological parameters on it was investi-gated. The total dose commitment from uptake inwater during 20 year period would be about 50 mrem.This dose is comparable to the total annual exposu-re?f rom natural background radiation. In 1983 year^'Cs content in some component of lake average was

following water 14-25 mBq.dm"'3, upper bottom 8-30mBq.g . down layer of,a«diment 9-15 mBq.g , Thecoefficient diffusion^ J'Ce from sediment to waterwa» equal 0.3-1.3.10 .

127ABOUT USE OF BROMINE-82 LABELLED ETHIDIUMBROMIDE INDNA INVESTIGATIONSKARIN LANGROCK. E.-J. LANGROCKRadiologxsche Klinik der Karl-Marx-Universitat,Leipzig, GDR

One of the developed methods to detect low dosedamages and their repair is the measurement of flu-orescence due to intercalation of ethidiumbromideinto non-histon-protein-chromatin-structures or so-called nucleoids after cell lysis and ultracentrifu-gation through a sugar-ethidium gradient. The sedim-entation of nuclear particles is influenced by theadded amount of ethidiumbromide (EB), the structureof nuclear acids, and their previous damage like ir-radiation. For more detailed in vestigations we tri-ed to label radioactive bromine-82 atoms as a partof the ethidiumbromide molecule. Basing on prelimi-nary investigations we can conclude; RadioactiveBr-82 labelled EB shows the same behaviour as usualEB and can give fluorescence after intercalation.The maximum of radioactivity in a sugar-EB-82 gradi-ent system containing lyaed lymphocytes or V 79 fi-broblasts is similar to those of spectrometric mea-surements. As there are established equipments forradioactivity measurements in institutes with radio-biological investigations programs it can be moreavailable to work with radioactive markers of theinteresting substance. Labelling of EB with radio-active bromine-82 can help in further elucidationof interacting molecular mechanisms regard to quan-titative relations.

1 2 8

THE EFFECTS OP N30NATAL X-IRMDEATION ON REPRCJUCTIONOP FEMALE

M.LEMRCZYK, B.A.AUBRMCH, M.G.SJCWIKOWSKA, A.K.GAJEWSKIftational~In8titute of hygiene, 00-791 Warsaw, Poland

Previous studies concemiwg the e f f ec t s of neonatalirradiat ion on female reproduction, with cne exception/Nash and Ragin, 1976, Life Sc iences , 1 9, 183 / , weredone with one dose usual ly higher than~5.2 Gy / 2 0 rar;s/#

In t h i s paper the e f f ec t s of X-irradiat ion of newbornClW/pzh female mice, with doses ranging from 0.06 t o2.56 Gy are reported.

Females were irradiated at the f i r s t Cay cf l i f e vdthlead shielded head, kept with mothers t i l l the end of4th week of l i f e , than Batted with unirrartiated malesand allowed to Ireed for one year .

S igni f icant ly increased s t e r i l i t y i n comparison withthe control unirreoiated mice was observed only i n miceirradiated with dene 1.26 and 2*56 Qy. Mean number ofl i t J;ere epd to ta l reproductive capacity were s i gn i f i cant lyclecreacecLin groups irradiared O.OBBB frct< O.64 to 2.56 Gy.There was no s icnif icexit difference i n the oncet oficprcdu'etion, however the f e r t i l i t y span WHS s ign i f i cant lyshorter in mice irradiated 1.28 and 2.56 Gy.

The irradiat ion cf ncv/boin CSTS/pah female mice withO.OB, 0.16 and 0.32 Gy doses not decrease the furtherreproductive capacity. The threshold dose for t h i s s t ra inl i e s probabl3r over 0,32 Qjr»

129

INACTIVATION MEuUNISM IN CELLS IRRADIATES BYGAMMAS AND NEUTRONSM. LokajigekInstitute ot Physics, CSAV, Prague, CSSR

Dsb are regarded as main lesions responsiblefor cell inactivation. Practically any single dsbcan inactivate the cell unable to repair such adamage of its. Dsb can be repaired, however, bynormal diploid cells. A part of cells is capableto repair all dsb formed by ionizing radiation.Only dwb remaining when the cell passes to mitosisprevent it from further repopulation. Thus, cellsurvival is given not only by the d«b number for-med at an applied dose but also by the rate d«bare repaired with. The influence of these twodifferent factors on the final effect has beenstudied with the help of a mathematical model ofinactivation mechanism. Survival curves obtainedin different times after irradiation ot yeastcells Saccharomyxes cerevisiae by gamea photonsand fission neutrons have, been analyzed. It hasbeen derived that the difference in cell survivalof diploid cells is caused mainly by different re-pair rates. This rate in the case of ganaa radia-tion is much greater than for neutrons, while theaverage number of dsb formed in cells hit by oneparticle of the irradiation beam is practicallythe same in both the cases. The results obtainedseem to be in a good agreement with the distribu-tion of energy deposited by secondary charged par-ticles as well as with the fact that chromosomesare not distributed uniformly inside the wholenucleus.

130

RADIATION-INDUCED AMPLIFICATION OF VIRAL DNA SEQUENCES INTE-GRATED IN THE GENOME OF CHINESE HAMSTER EMBRYO CELLS.CHRISTINE LOCKE-HtlHLE and PETER HERRLICHKernforschungszentrum Karlsruhe, Institut flir Genetik,D-7500 Karlsruhe 1, FRG.

Gene amplifications have been detected in several organismsand cell cultures (review: Schimke, 1984, Cell 37, 705). Theamplification process can be triggered by a variety of chemicalor physical treatments, most of which are carcinogenic. Theobservation of amplified oncogenes in human tumors suggestsgene amplification to be involved in carcinogenesis (Cairns,1981, Nature 289, 353).In this report we compare the effect of 60-Cobalt y-rays, 241-Americium alpha particles and UV light on the amplificationof an indicator gene: SV40 sequences integrated in a mammaliangenome.SV40 transformed Chinese hamster embryo cells (Co631) containabout 10 viral copies per cell genome.An increase in copynumber is tested by the dispersed cell assay in combinationwith specific ONA hybridization (Lavi, 1981, Proc. Natl. Acad.Sci. USA 78, 6144).All types of radiation induce up to 30 fold amplification ofSV40 sequences without producing intact virus. The amplifica-tion depends on dose of irradiation and on the presence of theSV40 origin and A gene. Amplification increases with timeafter irradiation. Maximum effect after alpha particles or UVis observed at day 3, after y-rays at day 6 after exposure.The decline thereafter suggests loss of the amplified se-quences due to lack of selection.

131EFFECT OF CYCLOPHOSPHAMIDE ON HEMOPOIETIC ORGANS INRAT. THE MORPHOLOGICAL CHANGES.N. MACKOVA. J. SPLIOVADept. Gen. Biol. UPJS, CSSR

Effect of cyclophosphamide (CP) on the morpholo-gical pictures of bone marrow, spleen and thymus ofrats was studied. Animals were examined till days30 after intraperitoneal application of CP in thedoses 100 and 200 mg/kg body weight. The applicati-on of CP caused the relative intensive decrease inthe hematopoietic activity. Myelopoieais recoveredtill day 20 and erythropoiesis till day 30. Changesin thymus persisted for longer period of time andreparation of lymphopoiesis was incomplete even theday 30 after cyclophosphamide application.

132

RBE OP FAST NEUTRONS(6.2 MEV), ACUTE AND LATE EFFECTS

E. MAODON

Central Institute of Cancer Research, Berlin, ODR.

The relative biological effectiveness (RBE) wasdetermined with a variety of test-systems for biolo-gical characterization of the Soviet cyolotron U-120,accounting for such problems as: dependence of RBEon single dose level, variance of RBE values tordifferent normal tissues, dependence of the RBE onfractionation as well as problems of late damagesand potential genetic injuries.Acute effects were measured by the criteria:inhibition of semiconservatlve DNA synthesis,induction of DNA repair synthesis, loss of cloneforming ability, inhibition of cell proliferation,short-term tissue damages, and survival rates.Late effects were measured by the criteria:long-term tissue damages and survival rates,analysis of lung fibrosis by means of quantitativehlstological image interpretation and determinationof hydroxyproline content. Genetic injuries weredetermined by the dominant lethal factors in post-meiotic stages of spermatogenesis. The experimentshave shown that the RBE values varied in dependenceon dose level, biological system, and time intervalbetween radiation exposure and manifestation in therange of 1.5 - 5.5. The RBE for genetic injurieswas found in the range of 2.5 - 5.5. For the lateradiation damages in skin, no significantly higherRBE values compared with acute injuries wereestablished.

133

MODIFICATION OP RADIATION EFFECTS, PHARMACOKINETICS,AND NEUROTOXICITY OF ISO-METRONIDAZOIEAND METRONIDAZOLE

E. MAODON, E. SCHRODER

Central Institute of Cancer Research, Berlin, 6DR.

Among the group of nitrolraidazoles, Misonidazoieand Metronidazole have been shown to selectivelysensitize hypoxic cells in vitro and in animaltumours. Because of the neurotoxlc side effects manyefforts are being undertaken in the search for newcompounds with equal radiosensitizing qualities butbeing less toxic. Comparative experiments have shownthat 4-nitroimidazole (Iso-Metronidazole) has simi-lar radiosensitizing ability in vitro and in localcontrol of mammary adenocarcinoma in C3H-miee thanMetronidazole. By the lower octanol/water partitioncoefficient of iso-Metronidazole (0.26) in relationto Metronidazole (O.96) investigations were carriedout for the distribution of both substances indifferent normal and tumour tissue.Generally, it could be established that concentra-tion in brain was much lower than in the othernormal organs and in the tumour.Pharmacoklnetic investigations on AUC yielded, overa longer period of time, a tumour/brain ratio of1.47 with iso-Metronidazole against 0.95 with Metro-nidazole. Using the grasping reflex it could bedemonstrated that the neurotoxicity of Iso-Metroni-dazole was much lower than that of Metronidazole.Because of the higher solubility, the greatertumour/brain ratio and a lower neurotoxicity iso-Metronidazole appears more appropriate than Metro-nidazole for clinical testing.

134

SURVIVAL AND DISEASE INCIDENCE IN MALE BALB/c AND C57BL MICEAFTER SINGLE, FRACTIONATED GAMMA OR d(5O)-Be NEUTRON EXPOSUREJ.R. MAISINRadiobiology Department, C.E.N./S.C.K., B-2400 MOL, Belgium

The relative biological effectiveness (RBE) of 50 MeV cy-clotron produced neutrons (0.02 to 3 Gy) compared to cobalt-60gamma rays (0.25 to 60 Gy) was determined with respect tolife shortening and causes of death after whole body singleand repeated exposure (10 daily fractions or 8 fractions givenat 3 h interval).Male mice of the C57BL and BALB/c strain at an age of 12 weekswere used to investigate the influence of differences in spon-taneous incidence of leukemias and cancers. More than 10.000control and irradiated mice were used.Many of the results have been published. Other studies arestill in progress. We shall therefore summarize only the mostimportant aspects and report newer data obtained on C57BL mice.In agreement with the observations in BALB/c mice our prelimi-nary results show that the total incidence of malignant tumorstends to be higher after fractionated gamma exposure than aftera single exposure, mainly as a result of a greater incidenceof thymic lymphoma, non thymic lyraphoma and all carcinomas andsarcomas.Single neutron irradiation results in apparently a linear lifeshortening in C57BL mice. The reduction in survival is mainlya result of an earlier occurrence of nonstochastic lung andpossible kidney lesions and liver tumors after 1.75 Gy and thy-moraa after 3 Gy. After fractionated or single neutron exposure,the total incidence of malignant tumors is about the same.

135DIAGNOSTIC RADIATION AND ADULT LEUKEMIA. THE RESULTSOF CASE - CONTROL STUDY IN POLAND

T. MAJLE, A.K. GAJEWSKI. M. KRZYZANOWSKI, 11.6. SLO-

WIKOWSKA, 2 . ftflzwinNational Institute of Hygiene, Warsaw, Poland

There is still considerable interest concerningthe relationship between low doses of radiation,such as from diagnostic exposures, and the risk ofleukemia* In this paper the r esults of case - cont-rol study in Poland are repeated. The interviews we-re collected from 958 adults with leukemia and thesame number of controls matched by sex and age* Onthe base of informations obtained during the inter-view all records of diagnostic exposure were collec-ted. The dose of radiation was expressed as a bonemarrow dose.

The estimated relative risk conected with bone--marrow dose above 0*2 radai did not differ statis-tically from 1.0* This result was consistent fordoses calculated on the base of data from the inter-view and for data from the nedical records, as wellas for the particular types of leukemia and for bothsexes*

136

TRITIUM IN ORGANIC COMPOUNDS OF BRAIN OF RATSEXPOSED TO TRITIATED WATER OR TRITIATED FOODDURING THREE SUCCESIVE GENERATIONS

Z.MAJOR

Central Laboratory for Radiological Protection,Warsaw, Poland

Wistar strain rats were chronically given tritlatedwater or tritiated food before and during pregnancyand thereafter continuously through two generationsuntil the delivery of F3 generation. The anim«lswere exposed to tritiated water or tritiated roodat activity of 37,0 kBq/ml /HTO group/ or 48,1JcBq/g /T-food group/. The third group was given un-contaminated food and water and was held as a con-trol* The incorporation of organically bound tri-tium /OBT/ into brain and its organic compounds we-re studied in adult rats /F females; Ft+F2, in Ju-veniles /F1+F9/ and in term fetuses /P./. Specificactivities ofOBT In brain of adult anlmals of F.and F» generations, lifetime exposed to HTO orT-fooO, were signiflcantly higher in comparisonwith F females exposed during mature life* Similarresults, except for proteins, were found for lipidfractions of brain» In this study has been evalua-ted the radiatlon dose rates absorbed in braintissue of two generations of rats and contributionof OBT and organic fractions to the dose rates. Thecontribution of OBT to the total radiatlon dose ra-tes reached about 10 per cent In brain tissue ofboth exposure groups. The contribution of llpids tothe dose rates from OBT was higher than proteins.

137

THE EFFECT OF PERORAL ANTIBIOTICS AND CHOLESTYRAMINON THE INTESTINAL EPITHELIUM REPAIR AFTER LOCALIRRADIATION IN RATSL. Handel and F. Moravek

Lab. Gnotobiology, lust. Miorobiology, Czech. Ac.Sci.v Prague, and Faculty of Medicine, CharlesUniv., Hradec Kralove*, Czechoslovakia [

It has been recently stated that in germfree •animals the radiation-damaged intestinal mucosa is ;better repaired due to the absence of intestinal ;microflora and microbially deconjugated bile acids. ;

An attempt was made to simulate these advantageous Iconditions in conventional adult male rats.

Experimental animals were divided into 4 groups:A - obtained in pelleted food «5 % of cholestyramin(bile binding resin; Questran^ Mead Johnson);B - neomycin, 1.5 mg and bacitracin, 80 U / ml ofdrinking water;C - obtained both cholestyramin and antibiotics;D - control group.

After the first 10 days of this treatment, ex-teriorized 3ejunal loops were irradiated (12 Gy,X - rays).Another animals were irradiated abdomi-nally with 8 or 12 Gy (gamma rays).

The average survival time after 12 Gy was 4.8,4.6 and 4.4 days in groups A, B, and D, but 6.8days in group C (P< 0.05). In irradiated intestinalloops as well as after abdominal 8 Gy irradiationa better repair of injured intestinal epitheliumwas found under histological examination on the !postirradiation days 8 and 12 in rats obtaining iboth cholestyramin and antibiotics when compared !with other groups. '

138

REPLICATIVE AND REPARATIVE DNA SYNTHESIS IK PERI-PHERAL LEUKOCYTES FROM GAMMA IRRADIATED RATSTS. MARINOVA. V. TENCHOVA, T. PANTEVInstitute ot Roentgenology and Radiobiology,Sofia,Bulgaria

Possibilities to exercise control over repairprocesses by means of radiomodifiers are an impor-tant current problem in radiobiology.Postradiation DNA synthesis in peripheral leuko-

cytes was studied in rats exposed to a 2-Gy or 6.8-Gy subsequent to pretreatment with adeturone (300mg/kg b.wt.)«Changes in DNA synthesis were estima-ted from rates of 3H-thymidine incorporation into,the DNA molecule.The kinetics of DNA synthesis were observed at 30min, 1, 3fan& 7 days postradiation.Depression ofincorporation was found to be maximum on day I.Thiswas also the sampling time showing a distinct pro-tective effect exerted by adeturone.In order to define changes in reparative DNA syn-

thesis, total synthesis was depressed with oxyurea(10-3 M).Protected animals exposed to 6.8 Gy showedappreciable stimulation of reparative DNA synthesisat 30 min postradiation.The portion of drug protec-tion affecting total synthesis (replicative-repara-tive) was accounted for predominantly by recoveryprocesses occurring at early times after irradia-tion.From the evidence obtained,the mechanism of ac-

tion of adeturone appeared to be related to repara-tive DNA synthesis.

139CIIROMATIN DEGRADATION I N IRRADIATED TIIYMUS-ATTEMPTSTO SEPARATE THE DAMAGED TIIYMOCYTE POPULATIONj.MATYASOVA , }.:.SKALKAInstitute of BiophysicSjCzechosloval; Acad.of Sci.,Drno, £SSR

Irradiation and action of several other noxiousfactors in vivo lead to intennitotic deatli of a num-ber of thywocytes, which is accompanied by nucleoly-tic degradation of cliroiiiatin to nucleosomes andtheir oligowors. In spite of isiauy comparative expe-riments performed both with cells and i&olated nuc-lei, no conclusions can be drawn as yet on tlie rea-son for tiie exceptional sensitivity of the lynpiioidcells, on the nature of the processes leading tocellular damage, and on the character of tiie nucle-ase involved in chromatin degradation. The tiiymuscontains cellular populations, differing in tiie pro-liferation capacity in the degree of achieved diffe-rentiation and also in the sensitivity to irradia-tion and other factors. We now attempted to elabora-te methods allowing separation of the damaged thymo-cyte population. A suspension of thyuiocytes, prepa-red from mice irradiated in vivo, was fractionatedby centrifugation on Lymphoprep-Verografin densitygradient. The fraction of rapidly sedimentiny cellscontained almost all dying cells and was tiie onlyfraction in which degradation of chromatin to nucle-osomes was ppoved. Another successful approach usedfor fractionating the irradiated thymocyte suspensionwas the filtration through cotton-wool layer in alow ionic strength solution. The present experimentsare aimed at comparing various properties of the un-damaged and damaged cellular populations separatedby both methods.

140

ANTAGONISM BETWEEN X-RAYS AND CADMIUM IN EMBRYONIC MOUSEDEVELOPMENT

C. Michel, R. Babini and Hedi Fritz-NiggliInstitute of Radiation Biology, University of Zurich,Zurich, Switzerland

The teratogenic effects of heavy metals can be modifiedby several chemicals and environmental factors. In this study,NMRI-mice were treated on day 7 and/or 8 of gestation withvarying doses of CdCl (0.5-2 mg/kg) and 200 kV >:-rays (0.5and 1.0 Gy). Lethal and gross malformative as well as cellulareffects like mitotic activity and cell death in the early eyeprimordium were evaluated 5 or 10 days after treatment.The prenatal lethality was not significantly affected by eitherexposure regimen compared to control. However, cadmium aloneinduced a variety of grossly detectable malformations. Therate of exencephaly induced by cadmium alone was drasticallydecreased when different sequential treatments with X-rays andcadmium were performed. Sceletal variations and malformationsalso occured at lower frequencies in combined treated groupscompared to cadmium alone. Intraperitoneal application wasmore effective in inducing exencephaly than the intraveniousroute and the antagonistic action between the two agents wasmore pronounced when the heavy metal was applied i.p. It ispostulated that this antagonism is due to the radiation-inducedsynthesis of metallothionein, a cadmium binding protein of lowmolecular weight.The histological analysis on day 13 of gestation showed asignificant increase of mitotic activity and less cell deathfollowing CdCl administration compared to control. There is,so far no evidence for antagonistic effects at the cellularlevel in the combined treated groups.

141THE RESPONSE OF MAMMALIAN CELLS TO 24-KEV NEUTRONS: THERELEVANCE TO RADIATION PROTECTION AND NEUTRON CAPTURE THERAPYA.J. MILL

Berkeley Nuclear Laboratories, CEGB, BERKELEY, Glos. UK.

There is currently considerable interest in the biologicaleffectivenss of intermediate-energy neutrons. Firstly, inradiological protection^since a large proportion of theneutron dose received by personnel around nuclear reactorsstems from this energy region; and secondly for boron neutroncapture therapy, since intermediate-energy neutrons provide apenetrating thermal-neutron flux profile without an accompany-ing high proton-recoil dose. AERE-Harwell, England, haverecently developed a relatively pure and intense beam of24-keV neutrons by filtering reactor neutrons with an iron,aluminium and sulphur filter. Plateau phase cultures of HeLacells were irradiated in this beam with doses from 0.3 Gy to5 Gy and scored for loss of reproductive ability. Preliminarydata indicate a relative biological effectiveness of ^ 3 com-pared with gamma rays.

142

CHROMOSOMAL ANOMALIES IN BONE-MARROW CELLS OF RATSEXPOSED TO HELIUM NUCLEIM. MILEVA. M. BULANOVA, I. GEORGIEVA, B. IVANOVInstitute of Roentgenology and Radiobiology,Sofia,Bulgaria

Experimental evidence is presented on dose-res-ponse relationships for chromosome aberrations inbone-marrow cells by exposing rats to helium nu-clei.Adult Wistar rats weighing 180-200 g were gi-ven acute doses of 0.5*1•0,2.0, or 4.0 Gy heliumnuclei with energy 4.0 GeV/nuclon at 0.1 Gy/secfrom a synchrophasotron accelerator of heavy nucleiRBE vaues were derived from regression coefficientsat equally effective doses for helium nuclei rela-tive to gamma quanta ('37cs,dose rate 1.95 A/kg).Anomaly types most frequently encountered were chromosome,followed by chromatid,fragments.Amounts ofaberrant cells increased linearly with dose: Y =0.42 + (14+0.11)D.Total breakage data were a fairfit to a linear-quadratic equation: Y=(11+0.26)D +(3.2+0,04)1)2.Values for RBE were equal to"~or some-wha t""a bove unity .

Prom the results obtained,it may be inferredthat:(a)Rat bone-marrow cells are highly sensitive to

accelerated helium nuclei.(b)The majority of chromosome aberrations are attri

butable to single-track events(Y=11D + 3.2D2).(c)Low-LET corpuscular and electromagnetic radia-

tions produce comparable cytogenetic effects.

143

ATTEMPT TO ASSESS EXTENT AND OUTCOME OF RADIATIONDAMAGE TO RATS USING LEUCOCYTE NUCLEIC ACID LEVELSM. MINKOVA. T. PANTEV, V. TENCHOVAInstitute of Roentgenology and Radiobiology, Sofia,BulgariaAn attempt was made to define dose-response for

amounts of nucleic acids(NA) in leukocytes and,onthis basis,obtain an estimate of the extent and. out-come of radiation damage.Male V/istar rats were usedthroughout.Dose-response relationships were exa-mined within the range 0.1-6 Gy at 3 days postradia-tion.The pattern of changes with time was observedup to day 30 after exposure to 0.5» 2, 4, or 8 Gy.Our findings showed the method used to be highly

sensitive,with decline in NA dose-dependent overthe range 0.1-6 Gy.Time-course study of the rela-tionships indicated: (a) maximum drop at 24 and 72hours and clear quantitative distinctions betweennonlethal (0.5 Gy),sublethal (2-4 Gy),and lethal(8 Gy = LD75/30) dose levels,especially at 24 hours;(b) appearance of an abortive peak by day 14 andreturn to normal values by day 30 ox nonlethal andsublethal doses only.With regard to the rat,it is concluded that 24-

hour drop in NA to 50% is typical for the nonlethal,to 40-20% for the sublethal,and to less than 20%for the lethal dose range.Absence of an abortivepe,ak by day 14 is presumably a sign of poor progno-sis.

144

EFFECT OP ROENTGENIZATION ON RAT LIVER NUCLEIAND MITOCHONDRIA AFTER HEPATECTOMYP. MIRKHAMIDOVA. S.K. KHALIKOV, L.SH. RABINOYICHAgricultural Institute, Tashkent, USSR.

Injury of hepatocyte nuclei and mitochondriais of important role in pathogenesis of roentgenirradiation disease. The activity of polyenzyma-tic systems and ultramicroscopical structure ofrat liver nuclei and mitochondria under diffe-rent doses of total roentgenization (50 - 1500r)in 20 hours after hepatectomy were studied. Ani-mals were killed in 30-60 minutes after roentgenirradiation. Subcellular organelles were isola-ted by differential ultracentrifugation.All do&es of roentgenization caused a decrease

in cytochrome-£-oxidase and NAD'H-cytochrome-j:-reductase activity of mitochondria and in cytc~-chrome-Cj-oxidase activity of nuclei. The decrea-se in enzymatic activity was shown to correlatewith elevation of dose-rate radiation intensity.

Moreover, we revealed the decrease in quantityof nuclear membranes pore complexes under 800rirradiation, that is connected with alterationsin transport systems. The transport of markedprotein from nuclei has been found to be 2 timeslower under roentgenizaticn. The decrease inquantity of mitochondrial cristas was observedalso. Comparison of obtained alterations showed,that injury of mitochondria appeared earlier,than that of nuclei.

Thus, suppression of rat liver polyensymaticsystems activity and alterations of mitochond-rial and nuclear membranes structure are deve-loping during 30-60 minutes after total roentgenirradiation in case of proliferative activity.

145

EFFECT OF IONIZING RADIATION ON DNA-SYNTHESIZEfG

CELLS OF BLOOD

E.MlgtfROV/. J.GXBOR, K*KROPXC"OVA*, D.PADO

Department of General Biology, Faculty of Science,P*J*3af£rik University, KoSioe, SSSR*

Incorporation of H-thymidine into blood of mice,rats and sheep after short-term labelling in vitro(without additional stimulation) was studied* Undersuch conditions the precursor uptake indicates thefrequency of DNA-syntheslzing cells, whioh repre-sent - at least part of them - circulating haemo-poietio CFU* The animals were exposed to whole-bodyX-ray, gamma or gamma-neutron irradiation undervarious conditions* The results suggest that thecourse of changes in the DNA-syntheslzing cell fre-quency in various kinds of mammals and under variousconditions of irradiation is similar* The commonfeature of the changes lies in an Initial drop whiohis followed by an increase in the DNA-syntheslsingeell frequency in the blood at 7-14 days both aftersingle exposure and after the start of continuousexposure to irradiation.

146

h'ADIOGIOLOGY AND THE CONCEPT OF INDIVIDUALIZEDCANCErt THEKAPY

K.H. MERKLE

Central Institute for Cancer Research of the GDUAcademy of Sciences, Berlin, GDli.

After a first step of cancerogenesis the furtherdevelopment of the tumor is an individual process.At the end of this process the tumor is formed asan individual in the individual. The individualityof cancer exists on organ, tissue and cell leveland includes individual tumor-host-relationships.The growing understanding of the biological indivi-duality of human tumors has increasingly influencedour therapeutic thinking. A detailed analysis andconsequent therapeutic consideration of clinicaland biological individuality of human tumors mayoffer real chances for improvement of cancer thera-py. Considering the extend of our knowledge abouthuman tumor cell biology it seems to be necessaryto go far beyond world-wide accepted TNM classifi-cation and histological typing. The current know-ledge of cell kinetic and other parameters may giveimproved conditions for choosing optimal fractiona-tion schedules. New imaging techniques give thechance to follow up changes in tumor characteristicduring radiotherapy. Above all they allow a moreprecise definition of target volume, a deminuationof irradiated volume and thus a possible increasein total tumor dose. The concept of individualizedradiotherapy is a challenge to radiobiologists fordeveloping and introducing new techniques for usein clinical practice.Its necessary and possibleeven today to realize this concept in radiotherapythough with certain limitations. To overcome thelack of dates demanded will be the task of radiobi-ological basic research as well as of producers ofequipment.

147

COMPARISON OP CHEMICAL AND UV MUTAGENIC ACTIVITYQUANTITATIVE PHYSICAL CHARACTERIZATIONK» M(5POS. S. GXSPAR, GY. RONTO"

Institute of Biophysics, Semmelweis Medical Univ.Budapest, Hungary

For the quantitative characterization of the mu-tagenic effect of chemicals in our environment thephage inactivation due to the thymine dimer produ-ced by UV irradiation was used*The so called mutagenicity index or dimer equiva-lent dose is a physical quantity characterizingthe mutagenic activity of the chemical and causessuch an amount of inactivation as on the averageone thymine per phage* The process is applied as anin vitro screening test. The test system is verysimple: T7 phages and E. coli host cells. Its advan-tages} it is quantitative, it takes into considera-tion the kinetics of the chemical effectt it israpid and fully automated. A number of significantresults are presented (compared to other in vitrotests) and the apparatus developed for the measu-rement of the mutagenicity index as well.

148

INFLUENCE OF SINGLE TOTAL. BODY GAMMA RADIATION ON

CELLULARITY AND LIPIDS IN BONE MARROW OF RATS

A.MOLCANOVA, I.AHLERS


Kosice, CSSR

Data of the last years underlined the partici-

pation of bone marrow adipocytes in stimulation of

haemopoiesis. Number of papers has documented the

decrease in cellularity and changes in lipid com-

position of irradiated bone marrow. In our study

we have aimed at mutual relations between both of

these changes.

In femoral bone marrow there were followed the

cellularity (number of nucleated elements per mg

of bone marrow) and the concentration of triacyl-

glycerols (TG) and phospholipids (PL). These para-

meters were investigated 1,24,48,72 hs after irra-

diation of 14,4 Gy, lh,1,2,3,5,7 days after the

dose of 9,6 Gy and 1,2,3,5,7,14,21,28 days after

the dose of 7,2 Gy gamma rays. Generally, we have

found dependance of cellularity and PL decrease on

radiation dose used and on the time* of analysis

after exposition. The radiation increased the con-

centration of *G t with some time delay compa -

red with the ch& f another paramaters.

149THE POSTNATAL DEVELOPMENT OF THE ADRENAL GLANDAFTER IN UTERO AND IN PROGENESIS IRRADIATIONM. MOLDAVSKYMedical Institute, Samarkand, USSRAdrenal gland of 554 rabbits irradiated at diffe-

rent stages of prenatal development of rabbits bornfrom mothers irradiated 0.5-9 months prior to copu-lation of healthy male and rabbits born from healthyparents were subjected during 6 months of life tostudy changes in cortex and medulla which includedhistology, histochemistry, morphometry, polarizationand electron microscopy. In utero irradiation at6-7, 13-14 and 21-22 days caused the retardation ofadrenal size growth, the deterioration of age chan-ges of histochemic, ultrastructural and morphomet-ric characteristics and the hypofunction of adrenalcortex and medulla. Tissue displasiaa, some of whichmay be estimated as recapitulation, changes of gro-wth and zonal differentiation are discovered in theadrenal gland of rabbits after irradiation on 6-7orl3-14 days of prenatal life* Normalization ofchanges caused by prenatal irradiation don't takeplace during postnatal development. Alteration ofcorrelation between adrenal cortex and medulla, de-formation, discomplexation and decrease of growthof adrenal cortex zones, retardation of differentia-tion and hypofunction of zona glomerulosa, fascicula-ta, medulla are found in posterity of female rabbits,irradiated 0.5-6 months prior to copulation. Thepossibility of normalization of several signs wereevident by prolongation of interval between theirradiation and female rabbits copulation to 6-9months.

150

THE RBE OF 24 keV NEUTRONS FOR V79 AH 1 CELLSGR MORGAN and CJ ROBERTSEnvironmental and Medical Sciences Division, B.364,AERE Harwell, Didcot, Oxon, 0X11 ORA, United Kingdom.

Interes t in boron neutron capture therapy for inoperablebrain tumours has been stimulated by encouraging reports fromHatanaka in Japan. Boron has a large cross section forcapture of thermal neutrons but neutrons of such low energyare unable to penetrate beyond the surface t issue to reachdeep-rooted tumours. This drawback can be overcome by usingneutrons of higher energy, eg 24 keV, which are converted tothermal neutrons in the brain t i s sue . The effectiveness ofsuch an approach may be limited by the RBE of the neutronsemployed for scalp t i s sue . To establ ish the RBE of 24 keVneutrons, V79 ce l l s were grown to plateau-phase and irradiatedwith a f i l te red beam of neutrons from a reactor . The beamcontained 95% 24 keV neutrons and gave a dose rate of 0.18Gy h~ ' . Preliminary evidence from cytogenetic and survivalanalyses suggested that the dose response was l inear up to4.8 Gy. The degree of damage per unit dose was similar tothat found af ter i r rad ia t ion with neutrons of 2.) MeV.Further studies are in progress to es tabl ish the effect ofdoping the ce l l s with Boron.

151

H3-CORTISOL-BINOING MACR0MOL3CULES IN TH3 DEVELO-PING CHICKEN HMBRYOS TISSU3SL.A.MURTAZAEYA. D.Kb.KHAMIDOV, V.D.MAKARKINBiochemistry Institute, AS UzSSR, Tashkent, USSR

The macromolecules binding iP-cortisol withhigh affinity have been found in the chicken em-bryos lung and liver cytozol. The macromoleculeshave restrict number of the binding sites and aresaturated when hormone concentration ±e low, about10 M. The analysis of the specific binding chartsin oketchard coordinates showed the presence of one

ft. —1type binding sites with the same Kaaa about 10 ^1in the macromolecules found. The highest H -corti-sol binding (on the 1 mg of the studied tissue pro-tein) was seen between the 13th and 16th days ofambryo development. Later the binding decrease wasseen till the end of the first day after the hat-ohing out, 5-day chicken showed a slight increase.

The additive tests of pH and thermolability,providing the optomal binding, proved that the re-vealed macromolecules are identical with the glu-oocorticoids found in other mammalian and chickenembryos tissues.

152PROSPECTS ON REMOVABILITY OF RADIO-ALKALINE EARTHESBY CRYPTANDSWHiHELM H. MULLEBNuoiearbiologie D-8042 Neuherberg FRG

Removal of radioactive alkaline earthes (RAE) ofSr, B« and Ra is possible by cryptand 222 (1). *tdepends almost on the presence of these radionucli-des (RN) in the extracellular space (ECS). The ECSmay be completely exhausted from RAE as it has beenshown in the case of Ba-133 (2), where the effectof removal reached 74 % five minutes after the in-corporation of the RN and 25 % sixty minutes afterincorporation. These effects were achieved by meansof a dose of 167 /UM (222)/kg i.p. in rats. A doseof 200 /uM(222)/kg achieved in the case of Sr-85incorporations after 10 minutes a treatment effectof only 37*5 % and 60 minutes afterwards an effectof 10.3%, though the ECS retentions correspond withvalues of about 70 % reap. 27 % of the applied RN.This decreased effect is caused by the 1.5 unitslower stability constant of the Sr-(222) cryptate,which is still less in the cases of incorporations(Sr+Ra), requires elevated (222)-doses, exceeding theactual threshold of the acute Doaia letalis media ofthis cryptand.

(1) W.H. MOller et al.i Nat. wiss.r (1970)57, 246;(1974)61, 455* (1977)64, 96.

(2) W.H. MQller; TEMA 5 (1984) Aberdeen, Scotland.Contribut. No. 2223 of Contract Bio-D-365-81-D ofCommission of EC.

153

DOSIMETRIC CONDITIONS FOR SYSTEMIC AND LOCAL INDUCTION OFOSTEOSARCOMAS BV BONE-SEEKING RADIONUCLIDESW. A. MULLER, U. LIN2NER, E. H. SCHAFFERAbteilung fiir Pathologie der GSFD-8042 Neuherberg, F.R. Germanyin association with EURATOM

Experiments performed with i.p. injection of short-livedalpha- and beta-emitting bone-seekers in mice showed inci-dences of osteosarcomas in dependence on skeletal dose andalso to a high degree on the distribution of dose with time(dose rate, fractionation and protraction). In all thesecases it was, however, not possible to deduce definite re-lations between local doses and anatomic site of the bonetumours. It could merely be stated that the axis-skeletondeveloped more than 60* of all observed tumours in case ofalpha-emitters and $0% for beta-emitters though the meanskeletal doses were always higher in long bones than those inthe vertebral column (Health Physics 35, 33-55, 1978).

A French research group (Setn. HfipT. Paris 58, 1684-1689,1982) developed recently a method in order to induce localosteosarcomas by i.m. injections along the tibia shaft with aradiocolloid of 144Ce (beta-emitter, 285 d half-life). Thequestion arose whether in this case also short-lived radio-nuclides could be used. First distribution studies in ourlaboratory indicated that the beta-emitte." ^?Lu (5,7 jhalf-life) could be successful: when this isotope was appliedin colloidal form, more than 95< of the activity stayed atthe injection site and less than IX reached the liver (butca. 5% of the activity was found in the liver with thel44ce experiments). The short-lived alpha-emitter 22?Thwas also considered in this experimental series and localdoses were determined.

All in all, it seems that for the induction of a localosteosarcoma more than the ten-fold local skeletal dose isnecessary compared with the conditions obtained after sys-temic application (i.p. injection) of bone-seeking radio-nuclides.

154

CHROMOSOMAL DAMAGE AFTER HEAVY ION EXPOSURE

W. Muller, HXS. Miltenburger, TH DarmstadtG. Kraft, GSI Darmstadt, BRD

Chromosomal aberrations induced by heavy charged particlesexhibit a different time dependence and a different distribu-tion of the various types of chromosomal damage compared toX-ray induced damage. In experiments at the UNILAC, exponen-tially growing V79 Chinese Hamster cells are exposed to theparticle beam and mitotic cells are prepared for chromosomescoring after a 4 hour period of colcemid treatment. The timeinterval between irradiation and chromosome preparation wasvaried between 0 and 45 hours. As reported earlier 2

, m thefirst 4 hours after irradiation a high number of chromosomaldisintegrations is observed in which a whole chromosome or asignificant part of it is scattered into small pieces. The highrate of chromosomal disintegrations is also accompanied by ahigh incidence rate of single break events (breaks, fragmentsand deletions) compared to the incidence of the more complexaberration figures like exchanges, ring and dicentrics. Thisdistribution, in which the single break events dominate thedistribution pattern, is also observed for longer timeintervalls after exposure and is in a strong contrast to theX-ray experiments. For X-rays, single break events andmultiple break events are observed with comparable incidence.This finding can at least be partially understood by thedifferences in the energy deposition between X-rays andparticles.

1 W. Muller et al. GSI Scientific Report 1982, p. 1872 W. Muller Dissertation TH Darmstadt 1985

155

KINETICS OF MICRONUCLEUS FORMATION IN PREIMPLANTATION MOUSEEMBRYOS

MULLER, W.-U.; STREFFER, C.

Inst. f. Med. Strahlenpysik und Strahlenbiologie, Essen, FRG

Micronuclei are either acentric chromosome fragments or -probably less frequently - whole chromosomes which are foundin the cytoplasm after mitosis. They are a sensitive markerfor cytogenetic effects after exposure to mutagens. Threeproblems will be dealt with in the following: 1. Is there arelation between the number of micronuclei and the time,which has elapsed between irradiation and the firstpost-irradiation mitosis? 2. Is the formation of micronucleirestricted to mitosis or can they be generated also duringinterphase? 3. Are micronuclei removed during interphase by,for example, enzymatic degradation? In particular, solutionof problems 2 and 3 requests a synchronous cell population.Therefore, preimplantation mouse embryos of the 1- to 8-cellstage were used, because their natural synchronism rendersany additional manipulations unnecessary. Results andconclusions: 1. Those embryos dividing early afterirradiation show a higher number of micronuclei than thoseembryos which develop more slowly. It is assumed that moretime for repair is available for the latter group. 2. Thereare no indications that micronuclei are formed duringinterphase after doses of 1 or 2 Gy X-rays. 3. There areindications that at least under certain conditions some ofthe micronuclei get lost during interphase. However,additional micronuclei are formed during the second and thethird post-irradiation mitosis.

156

RETENTION OF Ce IN RATS WITH DIFFERENT SEVERITYOF EMPHYSEMA

J. NAMENYI, A. GACHALYI, L.P. VARGA

"Frederic Joliot-Curie" National Research Institutefor Radiobiology and Radiohygiene, Budapest, Hungary

Emphysema is a prominent lung disease in themajority of human population and this chronicobstructive lung disease is mair.ly associated withthe inhalation of different types of airbornpollutants and cigarette smoking,. Because thediseased lung might be more sensitive to othernon-radioactive and radioactive pollutants exper-iments were initiated to compare the retention andelimination pattern of inhaled 1 Ce in healthyrats and animals suffering from a pre-existing lungdisease /pulmonary emphysema/ with different sever-ity. Emphysema was induced by inhalation of 5 #papain solution. Animals were exposed by inhalationto l^CeClj 1, 6 and 9 month thereafter. In theearly stage of disease, enhanced elimination of144<;e was stated. In the six months* group whenmainly mild emphysema has developed, no changesin retention pattern were observed. Animals withserious bronchial and peripheral disorders /9months* group/ exhibited increased retention ofl**Ce both in the trachebbronchial and alveolarregion of lung.

157

EVALUATION OF LUNG DEFENSE MECHANISM IK RATS WITHEMPHYSEMA AFTER l^Ce INHALATION

J. NAMFNYI, A. GACHALYI, L.P. VAHGA

"Frederic Joliot-Curie" National Research Institutefor Radiobiology and Radiohygiene,Budapest,Hungary

In chronic obstructive lung diseases caused byair pollution and smoking, the tracheobronchial andalveolar clearance play a crucial role in thedevelopment of these diseases. The defense mecha-nisms also play an important role in the protectionof diseased lung from secondary infection of radio-active and non-radioactive pollutants.In animals with different severity of papain-

induced emphysema the retention of inhaled i*^Cewas discussed in previous paper. In the same groupsof rats clearance function of the lung was evalu-ated by 5lcr labelled particles of 5 urn. Particleswere introduced into the lung one week beforel^Ce exposure and the elimination of those wasfollowed for 60 days. Six mo after papain inhalati-on, no changes in clearance activity were observedbefore l^Ce exposure. Radionuclide treatment dec-reased the mucociliary escalator only in some rats.Investigations of rats with serious emphysema re-vealed highly increased defense activity beforel^Ce exposure but this values were significantlylowered by inhaled Ce.Results presented here clearly show that defense

mechanisms in diseased lung is impaired by inhaledradionuclide and this impairment might be a co-fac-tor in the progression of obstructive lungdiseases.

158

CHANGES OF IJEVELS OF CERTAIN PROSTANOIDS IN THEBLOOD PLASMA. OF WHOLE-BODY IRRADIATED RATS

L. NAVRA*TIL. J. POSPfglL

Institute of Biophysics and Nuclear MedicineFaculty of General Medicine Charles University

Prague, C*S3R

Prostaglandins are ever active substanceswith a participation in a number of metabolicprocesses. Almost all the cells are able tosynthesize prostaglandins in responses to diffe-rent stimuli. Thus, in body liquids, prostaglan-din levels also exert variations during differentpathophysiological processes.

In our work, we followed changes of thelevels of PGF2a, 6-keto PGFia and thromboxan B9in the blood plasma of whole-body irradiated d

male rats, exposed to a subethal dose, dependingon time after irradiation and on the radiationdose.

The results indicate remarkable changesin the metabolism of prostanoids after theionizing radiation action.

159

META30LI3M AMD BIOLOGICAL ACTI/ITY IN THE COMBINED

APPLICATION OP AMBiiICIIUM-241 AND EXT3HNAL IONIZING

RADIATION

H. Nechev, P.Salovski, V.Shopova

Higher Medical Institute, Pleven, Bulgaria

i-Ietabolism and biological activity of Americiura-

24I introduced intratracheally in the form of nitrate

with an activity of 148 k3q/kg and external radiation

with an activity of 1,2 and 4 Cry were studied. The

distribution of the nuclide is of hepatoosteotropic

type. Radiation with 4 Gy decreases the contents of

the radioisotope in the lungs due to hyperemia in the

organ. In the liver, external radiation accelerates

the kinetics of the radionuclide. Non-demonstrative

changes in the classical haeraatological and biochemi-

cal blood patterns require more sensitive tests for

the estimation of the biological effect. The dyna -

mics of the lymphocytic nursleolar index has informa-

tive value for alpha-emitting radioisotopes. Cyto -

chrome P-450, aainopyrine N-demethylase and aniline

hydroxylase activities are inhibited earlier and are

specially marked in combination with 4 Gy. Results

cprrelate with ultrastructure changes in the liver

160

OSCILLATION IN STEM CELL PROLIFERATION AFTER 1.5AND 2.6 GY TOTAL BODY IRRADIATION

• .NSC'AS. V. ZNOJIL

Dept. of Pathophysiology, Faculty of Medicine,Charles University, 128 00 Prague, Czechoslovakia

The proliferation rate of haenatopoietic stemcells (CFU-s) was examined by the JH-thymidine sui-cide technioue in total body irradiated mice. Mar-ked oscillations, compatible with synchronous CFU-s proliferation, were recorded after the dose of1.5 Gy. After a dose of 2.6 Gy, the proliferationrate of CFU-s was constantly high several daysefter irradiation, suggesting an asynchronous in-tensive proliferation. Nevertheless, the prolife-ration also switched into that of synchronous wa-ves, on days 6-7 after irradiation when the CFU-spopulation regenerated only up to 6-10 % of thenormal. The findings show that following irradiat-ion the CFU-s proliferation rate is relativelylittle related to the CFU-s numbers. Furthermore,they describe a new phenomenon - the proliferationof CFU-s in synchronous waves.

161

RADIATION CARCINOGEKESISK. NEUMEISTERRadiologische Klinik und Poliklinik, Karl - Marx •Stadt, DDR

The problems of radiation carclnogeneeis arein discuasion, especially in the field of lowradiation doses. The paper demonstrates new inter-national results in this topic and reports *n .the author's clinical investigations of radiation-induced carcinoma and problems of medical expertopinions in these cases.

162EFFECT OF HYPOTHERMIA ON RADIOSENSITIZATIONA.H.W. NIASRichard Dimbleby Department of Cancer Research, St.Thomas's Hospital Medical School, London SE1 7EH

Mice are often used for the pre-clinical testingof radiotherapeutic strategies involving the radio-sensitization of hypoxic tumour cells. The usualworking hypothesis assumes that oxygen or some otherelectron-affinic substance will directly modify theradiation chemical response of such hypoxic cells.This is then assayed in terms of radiobiological en-hancement. Any change in the proportion of tumourcells which are hypoxic at the time of assay willalter the result, however. Such a change may be ex-pected to follow from a period of hypothermia duringwhich metabolism may be significantly reduced.

Mice have a poor thermoregulatory mechanism whenthey are inactive and hypothermia may easily occurunder experimental conditions. Thus the core tempera-ture of C3H mice falls to 31 C with anaesthesia andto 33 C with Misonidazole alonef after the 30 minutetime interval often used in radiosensitization expe-riments. Even lower temperatures occur after longertime intervals.

When mammary tumours are treated with single do-ses of radiation, the radiosensitizing effect of ny-perbaric oxygen is increased from an enhancement ra-tio of 1.2 to 1.7 if the mice are anaesthetized.When the associated hypothermia is prevented by war-ming the mice, this radiosensitization is reduced*

If radiosensitizing agents are being tested usingmice, hypothermia may contribute to hypoxic cell ra-diosensitization by an effect which is additional tothe radiation chemical mechanism under trial. Suchhypothermia is not found in clinical trials.

163

WEAK POINTS OF DOSE ASSESSMENT MODELS DUE TO RELEASE

FROM COAL POWER PLANTS.

T. NIEWIADOMSKI* M. JASINSKA, P. WASIOLEK

Institute of Nuclear Physics, Krakow, POLAND

In order to estimate dose equivalents due to releases from non nuclear

industry and power plants one ought to know several parameters.

The values of most of these parameters are hitherto based on experience of

radiation protection in nuclear industry. Thus they deal with radionudidss in

fairly known chemical and physical form. This approach may be assumed now

as a very crude one as far » assessment of the effects of release of natural radio-

nuclides in fly-ash matrix is concerned. This was understood by Jacobi who

adopted some of the parameters mentioned above to this particular purpose

basing on rational premises. His approach was used in thelast UNSCEAR Report

for assessment of collective doses.

The radionuclides released by the non nuclear industry need not necessarily

move in the body and be eliminated from particular organs according to the

models developed for radionuclides encountered in nuclear industry. Therefore

it seems to be necessary to approach more closely to the non nuclear releases

i. e. to investigate more thoroughly the physical and chemical processes in

different type boilers, to apply the environmental transfer models with the

use of local dispersion conditions, and to develop* the more adequate metabolic

and associated dosimetric models.

164

TIIE EPPECT OP SMALL D0S3S OP IRRADIATION ONLYMPHOCYTE RECEPTORS OP CHICKEN EMBRYOS,NISHANBAEV K.N.. SHPOLJANSKY Ju.V., ALLAJA-RCVA G.I., RUSTAMOVA R.Z.

Institute of biochemistry of the Academy orSciences of Uzbek SSR, Tashkent, USSR.

Ueveloping chicken embryos,irradiated beforeiiicubation with Co gamma-rays in the dose of0,029 Gr have been studed.Surface ioraunoglobuline(Ig) and receptors for

Fc-part of IgG on lymphocytes of bursa Pabriciichicken embryos were detected. Individual lym-phocytes, bearing Pc-receptors to Ig on 10 dayof incubation, of irradiated embryos were obser-ved by means of protein A,labeled with PITC,whereas the intact ones have done this on 11day. The surface Ig were distributed on lympho-cytes of irradiated embryos on 11 day of incuba-tion, whereas in intact ones it was seen on 13day,by immunoelectrone microscopy*Our results demonstrate that small doses of

irradiation accelerate the differentiation ofprecursors of immunocompetent cells in develo-ping chicken embryos.

165MECHANISMS OF RADIOSTIMULATION OF PLANTSNORALI NORBAYEV. ZAFAR NORBAYEVTermez State Pedagogical Inatitute after M.T.Aibek,Termez, USSRThe paper investigates the mechanisms of radiosti-

mulation of various plants organisms under the in-fluence of ionizing radiation. The results of measu-rements of electrophysical, physiological and biolo-gical parameters are compared at low doses of irrad-iation. At stimulating doses of irradiation the si-ze of electroconductivity gravity decreases in twen-ty four hours after the irradiation at the stimula-ting-plants. The analogical results were obtainedwhile studying the electrokinetical potentials. Theelectro-capacity of stimulating doses increases whi-le absorbing the ions of potassium and sodium incomparison with the unirradiated plants organisms.The investigations of watersoluble substances underthe influence of ionizing irradiation show that atlow doses the increase at some degree is observed.At stimulating doses of irradiation ofmaize plantsthe content of root isolation decreases for severaltimes. The measurements of green masses at such sco-pes of doses show the opposite process. The reducti-on of isolation of watersoluble substances throughthe root system is possible to use the express met-hod for characterizing the radiostimulation and ra-dios tability of plants. The suggested method is baa-ed on the redister of phase character of root isola-tion of sprouts at irradiation of various doses. Itis supposed that mechanisms of radiostimulation ofplants organisms is linked with the acumulation ofsome organic watersoluble substances but for thereduction of isolation through the root system.

166

ACCURACY REQUIRED IN CLINICAL DOSIHETRY

J.IIoyotnyInstitute of Radiation Dosimetry, Prague, CSGR

The cure rate and complication rate for differe-nt types of human ca:vjer were analysed by a nodelon the base of published data. The cure rates aswell as complication rates increased linearly whenplotted on a probit scale against dose in logarithm.The coefficient of variation, the ratio of one sta-ndard deviation to the dose of 5O'/i cure or complica-tion , was taken as an indicator. The cure rate wit-hout complications has been calculated, using deri-ved model, with data obatined from analysis of pu-blished response curves. The cure rates without com-plications were affected by the values of coefficie-nt of variation for cure and complications and bythe values for 50/u cure or complication dose. It wasconcluded, on the base of theoretically derived cur-ves for different values of coefficient o^ variationand different values of 50',..'. dose for cure and compli-cations and fiom clinically derived curves,that thetotal uncertainty of dose estimation would be betterthan + l',l to effect cure rate without complicationsnegligibly. In some cases (for example for supraglo-tic Ca) must be total uncertainty even better than+ 5/<j. The accuracy of dose estimation in radiothera-py was emphasized.

167

RESULTS OF INDIVIDUAL DOSIMETRY IN POLANDB.NOWAK, J.JANKOWSKI

Institute of Occupational Medicine, tddz, Poland

!n Poland measurements of individual dosesreceived by workers exposed to X-rays are carried outcentrally by Institute of occupational Medicine in todz.In 1984 19 000 persons employed in health service /81%/,industry l\1%f and research institutions /!%/ were moni-tored by film dosimeters. In last 10 years about 99%of all monitored population received annual dosesbelow 5 mSv I.e. 0.1 of annual limit. Doses higherthan annual limit occur seldom - only several casesa year. They are due to short-time exposure and notto the sum of systematically received high doses.

168MICRONUCLEI INDUCTION AFTER HEAVY ION IRRADIATION INA RAT RHABDOMYOSARCOMA IN VITRO AND IN VIVO USING AMONOCLONAL ANTIBODY TO BRDURD AND CELL SORTINGM. NtJSSE and S.B. CURTIS

G e s e l l s c h a f t fur S t r a h l e n - und Umweltforschung,F r a n k f u r t , FRG and Lawrence Berkeley Labora to ry ,Berke ley , Ca, USA.

Micronuclei found in interphase cel ls after irradiationrepresent mainly acentric chromosome or chrctnatid fragmentswhich are lost from the gencme of the ce l l during mitosis.Measuring the fraction of micronucleated ce l l s in a prolifera-ting cel l population the response of a tetraploid ra t rhabdo-myosarcoma cel l system to irradiation with X-rays and heavycharged-particles was studied. Asynchronous cel ls were i r radi -ated and the fraction of micronucleated cel ls measured whena l l ce l l s had divided. This fraction increased linearly withdose between D = 0 - 3 Gy for X-rays and D = 0 - 1 Gy for neonand silicon particles in the extended Bragg peak region. PBE-values were calculated for the various ions studied, theyagreed with RBE-values measured in the same ce l l system withother endpoints (survival in vivo and in v i t ro , tumor growthdelay). At low doses (D 1 Gy), irradiation with heavy ionsinduced more micronuclei per cel l compared to irradiation withX-rays, a consequence of the different spatial distribution ofdose in the ce l l nucleus. For comparison, micronuclei inductionafter irradiation was also studied in solid tumors using amonoclonal antibody to BrdUrd to detect cycling tumor cel lswhich were continuously labelled during S-phase with BrdUrd.The fraction of micro-nucleated cel ls was measured in dissocia-ted tumor cel ls sorted in a flow cytometer according to t e t ra -ploid DNA content and high BrdUrd content. The RBE-value forpeak neon irradiation agreed with data from in v i t ro experi-ments.

1-69

MUTATION FORMATION AND MAMMALIAN CELL INACTIVATIONBY HEAVY CHARGED PARTICLES

G.M.OBATUROV

Research Institute of Medical Radiology, Obninsk,USSR.

Biophysical model of mutation formation andmammalian cell inactivation is proposed. Themodel is based on the supposition that double andsingle strand breaks (DSB and SSB) of DNA causemutation formation. Mutations are formed as a re-sult of interaction of chromosome loci containingDSB (chromosomal exchange aberration - I-st typeof mutations), spontaneous transition of DSB tounrepaired lesions (terminal deletions) or mis-repair of DSB (2-nd type of mutations), and mis-repair of SSB (3-rd type of mutations). On thebasis of this supposition equations were deducedfor the yield of three types of mutations formammalian cells exposed to heavy charged particlesdepending on dose and LET. The equations take intoaccount track structure, specific energy Z dis-tribution in cells, cellular biological para-meters (DNA mass, nucleus volume etc. ).Radiosensitivity and inactivation section values

depending on LET were calculated for 5 types ofmammalian cells. Calculated data successfully cor-respond to experimental ones. As follows from thecalculations no more than 17 % of DSB participatein aberration formation, evidently those presentin DNA repeated sequences.

170

THE DOSIMETRI OP THE IONIZING RADIATION BYDENSITO-GEOMETRICAL PARAMETERS OP LYMPHOCITES

E.E. Ohanjanian, A.A. Ohanjanian

Sector of Radiobiology, the Ministry of Healthof Armenian SSR, 'fcrevan, USSR

The caryometrical analyse of lymphocites in peri-feric blood of rats was undertaken on the authomatictelevision analysator of microobjects in 3 and 6 ho-urs after general single X-ray radiation with dosesof I,75gr, 3,5gr and 5,25gr. It was shown, that themeanings of principal densito-geometrical parametersof nucleus (area, perimeter of the cut of nucleus,pseudooptical volume and area of surface of nucleus,coefficient of the form and voluminous coefficientof the form of nucleus) statistically reliably in-creased proportionally to the time and dose of radi-ation. The increase of parameters studied took placeamong big and small lymphocites mainly. The raise ofionizind radiation dose caused the significant in-crease of the ratio of big lymphocites quantity tosmall ones. The algorhytm of the early diagnostic ofradiation sickness was elaborated by using of themathematical methods of regression analyse and thetheory of image recognizing.

171PRONOUNCED DNA FRAGMENTATION FOLLOWING TREATMENT WITH BLEO-MYCIN AND WITH HIGH DOSES OF GAMMA IRRADIATION. A MICRO-ELECTROPHORETIC STUDY OF SINGLE MAMMALIAN CELLS

0. OSTLING and K.J. JOHANSONThe Gustaf Werner Institute, Uppsala, SWEDEN

Chinese hamster varian cells grown in_ vitro were treated withbleomycin or irradiated with high doses of 60Co-gamma rays(200 and 400 Gy) in separate experiments. DNA strand breakswere analyzed by using our newly introduced micro-electropho-retic technique to analyze single cells (0. Ostling and K.J.Johanson, 1984, Biochem. Biophys. Res. Commun. 123, 291-298).Bleomycin seems to act in a selective manner so that in somecells the DNA is heavily degraded while in others there isonly moderate damage or no measurable damage. This was thecase for cells growing exponentially as well as in confluentcells. To achieve the same magnitude of DNA fragmentation asin the most severely damaged cells after treatment with bleo-mycin the cells had to be irradiated with more than 200 Gy.This dose will introduce about 8 000 double-strand breaks percell. The molecular weight of DNA will then be in the range of10^-10° dalton, and free migration of DNA fragments will occurin electrophoresis.

172PRENATAL DEATH, CONGENITAL MALFORMATIONS AND CHROMOSOMALABERRATIONS AFTER NEUTRON- AND X-IRRADIATION OF MOUSE EMBRYOS1 HOUR AFTER CONCEPTION.S. PAMPFER, C. STREFFERInstitut flir Med. Strahlenphysik und Strahlenbiologie,UniversitStskiinikum Essen, D-4300 Essen 1, F.R.G.

Besides the well approved observation that irradiationduring the first days of gestation enhances the embryonaldeath, the occurrence of congenital malformations in survivorswas not constantly observed in previous experiments. Mouseembryos of the Heiligenberger strain were irradiated in vivo1 hour after conception either with neutrons (D+Be, averageenergy 7 MeV, dose between 12 and 75 cGy) or with X-rays(240 kV, 15 mA, 100 R/min, dose between 25 and 200 cGy). At19 days after conception, the following observations wereobserved: 1) the number of implanting embryos diminishessignificantly after irradiation and this loss is proportionalto dose, 2) the presence of deciduomata gives evidence to asecond reduction of the litters shortly after implantation,3) fetuses with exteriorized gut or exencephalia were foundwith a significantly higher incidence than in the controls,4) the development of the skeleton is almost unaffected byirradiation and the range of variety, abnormity and anomalyremains narrow, 5) the frequence of chromosomal aberrationsin metaphases of fibroblasts doubles in the fetuses withexteriorized gut and consits mainly in chromatide and chromo-some breaks. These data confirm that irradiation during thepreimplantation period may have also other consequences andnot only prenatal death.

173

EFFECTS 07 ABBTTOOKE OH MIBERAL AND PROTEIN META-BOLISM Of THE MAXILLOBEHTAL SYSTEM OP IRRADIATEDRATST. PAJfTEV. M. KHRISTOVAInstitute of Roentgenology and Radiobiology,Sofia,Bulgaria

Teeth and Jaw bones were examined for changesin soae parameters of mineral metabolism (calciumand phosphorus contents,mineralization coeffici-ent) and in protein synthesis (as indicated by™C-glycine incorporation rate) after exposingrats to 3-Gy gamma quanta in the presence of ade-turone.Alterations in the maxillodental systemwere compared with those occurring in skeletalbones (hip bone) under the same experimental con-ditions. .Radiation exposures were to 3-Gy '-"Cs gamma

rajs delivered at 2.2 cGy/sec from an IGUR-1 sour-ce. Drug pretreatment was by single I.P. injectionwith 300 mg/lcg adeturone given *5 min prior to ir-radiation. Sampling tises were day 7 and day 21postradiation.As indicated by our findings,adeturone-pretrea-

ted irradiated rats displayed a reduction in radiation Image to the calcified tissues investigated,as wall as less disproportion between mineral andprotein metabolism.

174

SELECTIVE RADIOPROTECTION AMD RADIOPOIENTATIONOF NORMAL AND MALIGNANT TISSUES OP MICE

T.PANTEV, J.MIRCHEVAInstitute of Roentgenology & Radiobiology; Insti-tute of Pharmacology, Sofia, Bulgaria

Investigations relating to modification of ra-diation effects in radiotherapy of malignant neopla-sms may be grouped into two general approaches:(a)Reduction of normal-tissue damage by drugs(radiopro-tectants or other agents(and (bj Enhancement of ra-diation damage _to tumor cells(radiosensitizer8;radio-potentiators;• «-<-

The paper analyst* a possible approach to sele-ctive radiomodification using substances possessingmarked protective properties for normal cells andexercising radiopotentiating action of malignant ti-ssues.

An example is shown in the properties of a Bul-garian radioprotector, Adeturone. Using this compou-nd under condition of combined radio- and chemothe-rapy of mice bearing Lewis lung carcinoma(i»m*) hasresulted in substantial difference in degree of da-mage between normal and malignant tissues* It wasestabilised that Adeturone in the most of schedulesused potentiated radio- and chemotherapy and thiseffect vas accompanied by concominant decrease inradiation damage in haemopoietic organs*

The node of action of Adeturone is thought tobe related to differences in SNA-aynthesis inhibi -tion time between normal and malignant tissue*

175

MOLECULAR MECHANISMS OP STIMULATING EFFECT OF

X-RAYS LOW DOSES ON ISOLATED MAMMALIAN CELLS.

I.M.PARKHOMENKO, Yu.B.KUDRJASHOV, Yu.Yu.CHIRKOV,B.A.RAEV

Moscow State University, Moscow, USSR

The action of Z-raye in doses O.O5-O.3O Gy on thecultured Chinese hamster cells was studied. Our ex-periments show a stimulation of initial adhesion tosubstrate of cultured cells. A maximum effect ofapproximately 140% (compared to the control) wasobtained with a dose of 0.15 Gy. Using fluorescentprobe 1,8-ANS we have shown some changes of cellmembrane properties, induced by low-doses ionizingradiation — diminishing of binding constant andquantum yield of 1,8-ANS fluorescence, and increaseof the number of binding sites for 1,8-ANS on thecell membrane as wall as the probability of energytransfer from protein tryptophanila to 1,8-ANS• Itwas appeared also a drastio affect of stimulatingdosea of X-rays radiation on the intraoellular le-vel of oAM?» It was shown that low-doses irradiati-on affects also the processes of ^-adrenergic ac-tivation of adenylate cyclase. These data show thatchanges induced In outer cell membrane by X-rayslow doses seem to cause Its main biological effect.

176

INFLUENCE OF PLUTONIUM 238 ON THE SENSITIVEENDOSTEAL LAYER IN MICEO.Pafizek, H.Mohelek*, V.HynCica and E.HartloviInstitute of Hygiene and EpidemiologyPrague, CSSR

Ultrastructure changes in the inner-surfacelayer of mouse femur metaphysis were studied ina group of 110-daya-old animals 48 hours afterplutonium incorporation. Solution of the radio-nuclide was injected locally into the preselectedbone area* Two groups of mice 110 and 350 daysold served as controls. Consistently with the li-terature data the bone structure changes as ob-served on electron micrographs were characterizedby the presence of pathologically altered orga-nelles affecting the shape of the cell and causingautolyeis, leading subsequently to denudation ofthe endosteum and it's direct contact with thecells of the marrow compartment. The "self-burial"of pathological osteocytes and their precociousdestruction close to the endosteal bone surfacewere clearly accountable for the limited formationof the bone lamellae in the matrix* None of thechanges observed was vadiation-specific for allof them could be found both in experimental andin control mice. However, the frequency at whichthese changes occurcd in plutonium-exposed animalswas significantly greater than in control mice.

177

CONFORMATION CHANGES OF BLOOD PLASMA PROTEIN MACBO-MOLECULES OF RATS AFTER THE COMBINED ACTION OF ^SrOR x " C e AND THE PHOSPHORORQANIC PESTICIDE PHOSALON2. PASKALEV. I. PEJANKOV. E. HADJIDEKOVAInstitut of Roentgenology and Radiobiology, Sofia,Bulgaria

There are partial studies of the conformation ofdifferent biological macromolecules (nuclein acids,proteins, etc.) in solution or isolated from orga-nisms treated with physical or chemical factors.Considerably restricted are investigations of bloodplasma protein macromolecules of mammals after comb-ined action of minimal effective doses and concent-rations of internal radiation and non-ionizing che-mical factors*

Experiments are carried out on rats "Vistar"treated with,combination of *Sr (per os, activity370 kBq) or J'*4Ce (i.p., 133.2 kBq) and phosalon(1/60 of LD.A/-SA)* Conformation alterations of ratblood plasma protein macromolecules are determinedfrom their dielectric constant frequency dispersion.

It ia settled that radiation causes prolongationof the macromolecules, phosalon provokes packing oftheir globular conformation. The combination phosa-lon — radionuclide increases conformation changesof plasma macromolecules in comparison the self-independent effect of the two factors and the deg-ree of these changes depends of time after thecombined application of these factors.

178

RADIATION DOSE-RESPONSE OF SOME GLUCONEOGENIC

AND ADAPTIVE ENZYME ACTIVITIES OF RAT LIVER

E. PAULJKOVA. M. TOROPILA. E. AHLERSOVA


KoSice, CSSR

The effect of accumulated doses of 3.83, 7.66,

11.49, 15.32 and 19.15 Gy of continuous gamma

irradiation during 7 days on gluconeogenic and

adaptive enzyme activities of rat liver have been

studied at 24 and 48 hours after each dose. Li-

near dose-response with a high correlation (r>

-0.98) was found between the activity of gluco-

se-6-phosphatase and the increasing radiation dose

at 24 hour. Similar but non-linear decrease was

seen in activities of tyrosine-, aspartate-, and

alanlne-transaminases. Increased fructose-1,6-

bi8phosphatase and tryptophan pyrrolase activi-

ties were found at both intervals with the simi-

lar course, the values being higher at 48 hour.

Accumulation of liver glycogen was seen in each

of the followed doses and in both intervals. In-

creased concentration of serum glucose was found

only 24 hours after irradiation.

179

HYPOXIC CELLS EJ TUMOURS - IS THE CRITICALPOPULATION FOR RADIOTHERAPY?IRINA I.PELEVINA, NATELLA A.GULVERDASHVILI,GBORGY G.AFANASIEVInetitut of Chemical Physics, Academy of Sciencesof the USSR

Numerous experimental data show that hypoxic cellsare responsible for the radioresistance of tumours.But there are new data that hypoxia was not alwaysdetermine the resistance of tumours to irradiation*Our polarographic investigations of the degree ofoxygenation in tumours of different types and diffe-rent sizes showed that:a-the variations in the deg-ree of oxygenation were large; b-pO_ level decreasedwith the growth of tumours and witn the distancefrom the periphery of tumours* The correlation bet-ween the degree of radlosensitlzation by metronida-zole (the hypoxic cells radlosensitizer) and thedegree of tumours oxygenation was not observed*Tumours reaotion to radiation is probably determinedby factors other then hypoxLa. Using the cloning ofoells (NK/Ly lymphosarcome) in diffusion chambersfollowing the local irradiation of tumours it wasshown that the radiosensitivity of cells from theoentral zones of tumours, was significantly lowerthan for the oells from the peripheral zones. Whenthe cells were cloned not immediately but 24 h af-ter irradiation the survival was increased only forthe peripheral oells, but insignificantly for thecells from central zones* So the repair of poten-tially lethal damages (PLD) observed only in welloxygenated cell population* These effeots result inthe leveling of hypoxio and oxygenated Do* We pro-pose that there is no repaire of PLD in the cent-ral parts of tumours under the conditions of severehypoxia. If this is so than the radioresistance oftumours is not determined by the existence of hypo-xic cell population but by some other factors*

180

COMBINED EFFECT OP X-IRRADIATION AKD DIBROMO-DUICITOI ON HIPERTHRRMIC TREATED P388 TIMOR

L. PERLAKY. ANNA FONAGY, E.J. HIDVEGI

"FJC" Natl.Res.Inst. for Radiobiol. and Radiohyg.,Budapest, Hungary

P388 solid tumor was used in the experimentsobtained after i.m. transplantation of ascites tu-mor. This tumor /P388/sol./ produced metastasis withhigh frequency in spleen and liver. An other type ofsolid tumors /P388/sol.HT/ was constructed by treat-ment of ascites tumor at 43.5°C for 1 h before i.m.transplantation. The P388/soX.HT tumor grew on thesame rate as non hyperthermic treated one but theoccurrence of metastasis was 10# only in liver, andnone in spleen. Both type of solid tumors wereX-irradiated locally. Irradiation with 6 Gy on firstday after transplantation increased the survival by29$ in P388/sol. and by 77# in P388/sol.HT. Signif-icant difference in volume of tumors, however, wasnot observed. This may be explained by the occur-rence of metastasis in P388/sol. while no metastasiswas found in P388/sol.HT irrespectively to irradia-tion. Tumor bearing mice were treated with 250 mg/kgdibromo-dulcitol one hour before 6 Gy Z-irradiationand one day after tumor transplantation. Survivalredoubled in P388/sol.HT as compared to P388/sol.

Authors described previously that in P388ascites tumor specific heat shock proteins /molecu-lar weight: 30, 55» 70 kD/ appeared on hyperthermictreatment in vitro /Perlaky et al., 1984, Byperther-mic Oncology, Vol. 1, 37-40, Taylor and Francis/.The synthetic rate of these proteins was studied insolid P388 tumor after combined modality treatments.

181

DOSIMETRIC SYSTEMS USED FOR ROUTINE IRRADIATIONS OPBIOLOGICAL MATERIALS

M.PeSek, Z.Prasil, M.R'erichova, V.Spev^cek, J.Simek

Institute for Research, Production and Applicationof Radioisotopes, 102 27 Praha, CSSR.

Irradiation of various biological materials becamerecently a more and more commonly used techniquea.Both large gamma sources and electron acceleratorsare used for radiation sterilizations, for the pre-paration of various bioactive materials etc. In theInstitute for Research, Production and Applicationof Radioisotopes three large b0Co gamma sources areused also for such radiation-biological applicati-ons* Absorbed doses are determined by various met-hods that are described in detail. Doses and doserates in thin layers are determined using the cellu-lose-triacetate foils, and for fast determinationsof exposure rates the semiconductor gauges provedto be the most useful. It is advantageous to combi-ne these methods with various computational proce-dures. If necessary, other dosimetric systems canalso be exploited. However, the results obtainedwith the methods described abo?e are sufficientlyprecise and constitute a good basis for the deter-mination of optimum irradiation conditions of bio-logical materials*

182

CHRONIC,LOW LEVEL TRITIUM CONTAMINATION EFFECTS

ON 125IUdR INCORPORATION IN DNA

ILEANA PETCU,T.BIRSAN,?LORICA TRIPAPUS,N.MOCANU

Institute of Physics and Nuclear Engineering,Bucharest, Romania

Chronic,long term (90 days) tritium contamina-tion effects are considered. The exposures wererealized by HIO ingestion as "ad libitum" admi-nistered drinking water to male Wistar rats inthe specific activities range O,37kBq/ml water--111 kBq/ml water.As a cell functional state sensitive parameter

especially for proliferative cells,the 125-IUdRuptake in small intestine and testis IiNA waschosen.Some observable effects concerning 125-IUdR

uptake as well as DNA extractibility were noti-ced even for the low contamination domain ofthe investigated range.The individual response variability appears

to be correlated with the amplitude of 125-IUdRuptake in DNA, suggesting an induced perturba-tion strongly dependent on individual physiolo-gical properties.After interruption of tritium exposures, fur-

ther experiments of the same kind reveal an ef-fect in the opposite direction in respect tothe previous one .The experimental data seem to indicate a radi-

ation-induced cell homeostasis alteration over-all effect. Further experiments should clarifyif this is due to cell membrane damage, enzyma-tic systems alterations or damage at the DNAlevel.

183

CONSEQUENCES OP LIFETIME TRITIUM EXPOSURE FORPOSTNATAL DEVELOPMENT OF RATS

Z.PIETRZAK-FLIS. I.RADWAN

Central Laboratory for Radiological Protection,Warsaw, Poland

Rats were chronically exposed to constant acti-vity of tritium in drinking water or to organicallybound tritium in food from conception to the 71-stday of life. The activities of tritium In drinkingwater were 185 and 370 kBq/ml and in food 144.3kBq/g. In all studied groups continuous exposureaffected growth of rats; in groups exposed to HTOthe effect was transient. A significant reductionin a relative weight of teetie was observed in agroup exposed to HTO at 370 kBq/ml,while spermproduction was affected in all groups.Ingest!onof trltiated food caused higher reduction In spermcount than HTO. Reduction in the oooyte number inthe ovaries of females exposed to tritlated foodwas higher than in ovaries of females exposed toHTO. The dependence of the survival of small oocy-tes on the dose rate and the total accumulateddose had an exponential character. Lifetime exposu-re affected development of motor performance; adelay in development of startle response and righ-ting reflex In all exposed groups was observed.The study of locomotor activity of males and fema-les lndloated significant hypoactlvlty at 370 kBo/mlwhile in females exposed to organloally bound tri-tium significant hyperactlvlty was noted. i

The present studies indicate that the biological jeffects of tritium depend not only on radiation !doses but also on the form of administered tritium. I

184

LO'J HOd., lUlJiaiKG RADIATIOH Oil PYItlDOilAL .iiZYLriSCOITION? IU HAT SItAIIJ

A.Pikulev, I.Khripchenko, V.LavrovaByelorussian State University, Linsk, USSK

It was sliov/n earlier that pyridoxal enzymesactivity depends on adrenal eland hormones level inirradiated animals. To understand the mechanism oflow dose ionizing radiation the experinents werecarried out on intact white rats with 120-160 gmass, on adrenalectornized animals v/hich were admini-stered catecholamines or glucocorticoids and on therats injected (i.p. or i.e.) with adrenaline, nora-drenoline, isadrina, phontolar:dne and propranolol.The study was conducted up oo the 30-th dc.y afterthe general X-ray radiation (0.4 Gr). -The contentof different forms of B^ vitairdne was deterr:iined insubcellular fractions o? rat brain.

It was established that the level of pyridoxaland pyridoxairlnphoophates in rat brain was radistr-ibuted between the subcellular fractions. We haveshown that pyridoxal coenzymes content depends onthe initial state of the hypophysis-adrenal system.The discoordination in pyridoxal enf-yiiie system dueto radiation may be connected with the change inthe level of Bg vitarnine phosphorylation fornswhich are their coenzymes. This proves the signifi-cant role of non-specific component in the actionof low dose ionizing radiation on animals.

185ADRENERGIC REGULATION OF ASPARTATE AIvIIHOTRANSl

ISOZYHES ACTIVITY WIDER IOV/ D0S3S 0? X-RAYSA.Pikulev. Li.Sholukh

Byelorussian State University, Minsk, USSR

The initial and trigger mechanisms of radion action on the hormonal control of cell metalam have been up to the present not elucidated,this connection, the study of adrenergic regulaof aspartate aminotransferase (AsAT) - the leadenzyme of nitrogen metabolism - is of perticulaiterest. The experiments were carried out on the .ver of white rats, with adrenaline, noradrenaline,isoproterenol as v/ell as adrenoblockers, proprano-*lol and phentolamine, adminestered i.p. 20 min be-fore the radiation (0.4 Gr). The isozymes were sep-arated by electrophoresis. It was shown that the ra-diation decreases the stimulating action of catecho-1amines on cytoplasmic isozyme of AsAT. The activityof AsAT in mitochondria (m-AsAT) increases under thesame conditions. The efflux of m-AsAT into cytoplasmincreases in a rat liver under the radiation follow-ing the adrenaline administration. In the irradiatedanimals the jtf-adrenoblocker propranolol completelyeliminates the activity rise of c-AsAT due to isad-rine in liver and partially - in a cardiac muscle.In the normal animals the isadrine stimulating acti-on was not blocked by propranolol in the cardiacmuscle and was partially blocked in the liver.

The change in the adrenergic regulation of AsATisozymes activity during the irradiation of ratspoints to the relatively high radiosensitivity ofsympatic system adrenergic chain and to the partici-pation of adrenoceptors in the mechanisms of indi-rect radiation action on AsAT isozymes.

186

RADIATION EFFECTS IN GEL5: LHUi-TErOPERATURE ESRSTUDIES ON REACTIONS OF COPPER-METALLdPROTEINSWITH WATER RADIOLY5IS PR'.JOUCIS

ANDRZEJ PLONKA and DIANA METODIEWA

I n s t i t u t e of Appl ied Radiat ion Chemistry, Lodz,Poland

The general func t ion of protein-bound copper

cons is ts i n e lec t ron t rans fe r to oxygen and i s f u l -

f i l l e d through different specific reactions which

so far were followed mainly in dilute aqueous solu-

tions. Dilute aqueous solutions are not adequate

models of biological systems in which there is main-

ly the bound water. 8ecause of that we have used

dextran gels in which bound water predominates. Em-

bedding of superoxide dismutase or ceruloplasmin

into dextran gels resulted in marked changes of re-

act ivi ty towards the primary products of water ra-

diolysis. Beside H0_ radical dismutation, observed

for dilute aqueous solutions, the reactions of su-

peroxide dismutase with electrons and of ceruloplas-

min with hydroxyl radicals were followed by the ESR

technique at low temperature.

187THE RADIOMODIFYING EFFECT OF GAMMAPHOS (WR-2721) ONIATE DAMAGE IN LOCALLY IRRADIATED RAT BRAIN

E.D.Plotnikova, M.Kh.Levitman, V.V.Shaposhnikova,YufV. Koshevoy and L.KJi. EidusInstitute of Biological Physics of USSR Acad.Sci.,Pushchino, Moscow Region, USSR

The ability of a radioprotector - ganmaphos tomodify the development of late (up to 18 months)focal injuries in the.rat brain after local whole -brain irradiation with 25 Gy was investigated bymeans of a microangiographical and morphologicalmethods. Gammaphos was injected intraperitoneally(350 mg/Kg)three minutes prior to X-irradiation(3 Gy/min). The number and the average size of ves-sels was scored automatically with the scanning setup/lAK (a television analyzer of biological objects)produced in the USSR. There was no obvious damageduring 12 months after irradiation. After 12 month75% of unprotected animals demonstrated gross vas-cular abnormalities and 50% - necrosis of braintissue; under gammaphos treatment these figuresdecreased up to 15% in both cases. Simultaneouslythe number of vessels decreased to 74% and theiraverage size increased to 140% of the control values.A significant radioprotective effect of gammaphosby these criteria was also obvious. The number andaverage size of vessels were 96% and 104% respecti-vely. The sudden late onset of brain necrosis afterirradiation with 25 Gy and the presence of radia-tion protection against it unlike the situationafter irradiation with 40 and 60 Gy indicate thatin this case the lesions were primarily vascularand necrosis by origin was secondary.

188

THE POSSIBILITIES OF BIOLOGICAL OBJECT IRRADIATIONAT CZECHOSLOVAK NEUTRON SOURCESPODZIMEK. F.. et al.J.E.PurkynS Medical Institute for Research and Post-graduate Study, Hradec Kra'love1

The basic dosimetric characteristics of radiationfields from:- horizontal channel of nuclear reactor WWR-S inftez

- isochronic cyclotron U-12O H in fteJdesigned for radiobiological experiment* are presen-ted.An irradiation channel was formed by reconstructi-

on of nuclear reactor thermal column, passagingthrough biological shielding to the edge of activezone vessel* Its dosimetric characteristic (kermarates, homogeneity of beam, relative representati-on of neutron and gamma dose) and technical parame-ters (channel diameter 1 m) are suitable for largerbiological object irradiation. For reactor averagepower 10 kW neutron kerma rate is cca 0.1 Qy.minwith relative representation of gammas kerma 10 to15 % and 35 to 45 % in free space geometry for 10cm and 100 cm distances from shielding filters,respectively.

Fast neutron partial irradiation of biologicalobjects is realized in cyclotron beam based on yBe(d.n) TJ reaction (energy of deuteron is 17 MeV,thick target).Special shielding coilimators enabledifferent beam size formation - 3*8 and 16 cm ofbeam diameters. At 50 cm distance (in beam axes)from Be-target the neutron kerma rate is 0.25 Gy.•min with gammas kerma relative representationlower than 3.5 %•The detailed results of dosimetric values measu-

rement and dosimetric method used are discussed.

189

KINETICS OF REPAIR AND MISREPAIR INMAMMALIAN TUMOUR CELLSW.POHLIT AND M*KRBMERGesellschaft fiir Strahlen- und Umweltforschung mbHPaul-Ehrlich-Strasse 2O, D 6OOO Frankfurt/Main

Repair of potentially lethal lesions was measuredunder three different physiological conditions:(a) in hypertonic medium (reduced repair),(b) in isotonic nutrient medium and(c) in conditioned medium (reduced misrepair).Kinetics of repair was determined by measuring cellsurvival and production of micronuclei in individualsingle cells.For quantitative analysis a cybernetic model wasused (Pohlit, Heyder, 1981, Radiat.Res. 87, 613),which takes into account the production oF irre-pairable and of repairable lesions, both beingdistributed in the individual cells according to aPoissonian distribution. Such a distribution wasfound experimentally to be present in cells irradi-ated with sparsely ionizing particles such as 30 MeVelectrons, whereas the distribution was "overdistri-buted" after irradiation with 14 MeV neutrons.Repair of potentially lethal lesions was calculatedin discrete steps during which misrepair occurswith a certain probability dependent on the numberof lesions present in individual cells. Agreementbetween calculation and experiment was found fora constant repair velocity and misrepair being pro-portional to the square of the number of lesionsin individual cells.It can be concluded that the main source of mis-repair is wrong rejoining of double strand breaksin the DNA.

190

IK VITRO RADIOSSNSITIVITY OF MURIK3 AND HUMANPROGENITORS OP HEM0P0I2TIC COLONIES IN PLASMACLOT DIFFUSION CHAMBERS (PCDC)Z. FOJDADepartment of Radiobiology WIHiE, Warsaw, Poland

Plasma clot diffusion chamber culture systemwas used to evaluate radiosensitivity of marineanf human hemopoietic ce l l s . Diffusion chamberswere f i l led with ce l l suspension in medium consi-sted of MEM Dulbecco enriched with PCS and humanAB citrated plasma (0.1 ml per ohamber), X-lrra-diated with 50,75,100,125 and 130 oGya and implan-ted intraperitoneally into phenylhydreeine-pre-treated and Z-irradiated mice. Radiation survivalcurves for murine CPU-E, BFU-E, CFU-G-3 and CPU-G-8, human fetal l iver and adult bone marrow ery-thro- and granulopeietie ce l l s were determined.D for aforementioned hemopoietic ce l l s were ca l -oSlated as follows}mouse;

Colony Forming Unit-Erythroid (CFU-E)j 35.9 eGysBurst Forming Unit-Erythroid (BFU-E)t 109.7 cGyaColony Fozning Unit-Graauloid-3 day (CFU-G-3)i

53*8 cGysColony Forming Unit-Granuloid-6 day (CFT7-G-6):

142.4 oGyahuman fetal livers

oommitted erythropoietio oel l j 52.9 oGys•ommitted granulopoietlo ce l l : 46.3 oGys

human adult bone marrowtoommitted erythropoietio oe l l : 91*9 oGys0ommitted granulopoietio ce l l : 106.3 cGys

191RBE-DETERMINATION OF ACUTE IN VIVO-EFFECTS FROM VERYLOW DOSE WHOLE-BODY EXPOSURE WITH DIFFERENT RADIATIONQUALITIES BY THREE IN VITRO ASSAYS

W. PORSCHEN, H. Miihlensiepen, J. Marx, C. Lindberg,J. Booz, L.E. Feinendegen

Institute of Medicine, Nuclear Research Center,P.O.B. 1913, D-5170 Jiilich, Germany, Federal Republicof

The incorporation of i.v. injected 125-Iodo-deoxy-uridine (125-IUdR) into DNA of mice is reduced bywhole body exposure to ionizing radiation. The effectis time- and dose-dependent and has its maximum atabout 4 hours after irradiation. More sensitive inthe low dose range is the incorporation of 125-IUdRinto bone marrow cells by in vitro labelling 4 hoursafter whole-body exposure. Irradiation of mice in-creases also the thymidine concentration in the mouseblood serum. The elevation of the level of thymidineabove its physiological equilibrium concentration inserum even at doses of 0,01 Gy is also dose- and timedependent and concordant with the reduction of traceruptake into cellular DNA of bone marrow cells. In thelow dose range the effects are related to a time- butnot dose-dependent inhibition of the cellularthymidine kinase. The present paper compares theeffects ofêxposure of mice to gamma-rays and to fastneutrons (E = 6 MeV) on (a) TdR concentration in theblood serum, (b) the inhibition of 125-IUdR uptakeinto bone marrow cells, and (c) on the enzyme activityof the cellular thymidine kinase.

After fast neutron irradiation the RBE amounts toone in the low dose range (D - 0.1 Gy) and increasesto 1.5 - 2 in the higher dose range.

192

THE EFFECT OF WHOLE-BODY IRRADIATION ON THE OCCU-RRENCE OF CHEMICALLY INDUCED TUMORS OF INBRED MI-CE WITH DIFFERENT ACTIVABILITIES OF THE AHH-SYS-TEMJ. POSPfSlL, J. VLXSKOVi, P.POUC'KOVA, J.POLfVKOVA'

Institute of Biophysics and Nuclear Medicine,Prague, SSSR.

On four atrains of inbred mice, which werechosen according to the genetically conditionedactinability of the arylhydrocarbon-hydroxylasesystem, an effect was checked of the repeatedwhole-body exposure to Co T*-rays on the rateof occurrence and time sf origination methylcho-lanthrene induced tumors. The repeated whole-bodyirradiation of mice neither increased the rateof the tumor occurrence nor affected the time ofthe origination of methylcholanthrene inducedtumors. On the basis of these results we considerthe genetically conditioned metabolism of precar-cinogen and not an InterTention of radiation intoimmunologie processes of the organism to bea prevalent mechanism.

193

ENHANCEMENT OF POSTIRRADIATION HEMOPOIETIC RECOVERYIN MICE BY INDOMETHACIN TREATMENTM. POSPlSlL. 3. NETfKOVA, A. KDZUBlKInstitute of Biophysics, Czechoslovak Academy ofSciences, Brno, Czechoslovakia

The effect of the nonsteroid anti-inflammatorydrug indomethacin, a potent prostaglandin synthesisinhibitor, on the recovery of hemopoiesis in sub-lethally irradiated mice was investigated. Male(CBA x C57BL/10)Fi hybrid mice irradiated with sin-gle wholebody sublethal doses of gamma-radiation(""Co) were used. Indomethacin (Confortid, DumexA/S, fyfbenhaven) was injected aubcutaneously atdo8es of 0.1 mg per mouse two hours after irradia-tion and successively at daily intervals over 5 or10 post irradiation days. A five-day period of indo-methacin treatment was found to increase the endo-genous spleen colony formation, radioiron incorpo-ration into the spleen, as well as cell prolifera-tion in the spleen as registered by ^Î-iododeoxy-uridine uptake in the organ. Lymphocyte and granu-locyte counts in peripheral blood were increased inmice given indomethacin up to the 10th day afterirradiation. The results of the experiments pre-sented are in agreement with the observations ofSklobovskaya et al. (1984, Stud, biophys., 102, 41)and can be explained by the inhibitory effect ofindomethecin on the prostaglandin synthesis underthe assumption that prostaglandins exert antipro-liferative regulatory influence on hemopoietic cellpopulations (e.g. Gentile et al., 1983, Blood, 62,1100).

194

COMPARATIVE SPIR-LABEL STUDY OF TBITIATED WATER-BETAIRRADIATED A5D ARTIFICIALLY AGED ALBUMINSE.A.PREOTEASA, NICOLETA GRECV, V.V.GRECU, A.ENULESCV,M.MOCANUCentral Institute of Physics, IFIN-18, BiophysicsGroup, R-769OO Bucharest, Magurele, Romania

The conformational changes produced in vitro inalbumin by beta irradiation in tritiated water(HTO)solution and by ageing have been studied vitb spinlibels. Bovine serum albumin (BSA) fraction V vasincubated at U6mg/ml in phosphate buffer (pH 6.8)with HTO at 0-5°C for 37 days and cumulated a doseof 26Gy/al solution. Rabbit serum albumin (RSA) wasin vitro aged by storage in buffer at 37°C for 18months (method by D.Onica). Both BSA and RSA werelabeled with Tempo-maleimide (MSL). TO monitor onlyconformational changes due to HTO irradiation, theeffect of global MSL-BSA tumbling in ESR spectra waseliminated by adding sucrose in excess. The evalua-tion of 2A&Z hyperfine splitting was improved by lo-cally fitting each spectrum's extrema with gaussians;the observed differences passed Student's test. InHTO-beta irradiated BSA, 2A£Z surprisingly increasedwith 0.85*0.29 G, in contrast to a 1.91- 0.U5 G de-crease observed in aged RSA, as well as to effectsreported so far for various modifying treatments(except polymeryzation). Both in irradiated and inaged albumin a single free SH group per moleculeremained MSL-acceasible. While in aged albumin theenvironment of the MSL-binding Cya3k SH group isknown to become more open by intramolecular S-S in-terchange catalyzed by this free, position-conservingSH, the more hindered MSL motion in HTO-incubated BSAsuggests that the beta irradiation accompanied byformation of water radicals and peroxides might ca-talyze another kind of S-S interchange, possibly as-sociated with a free SH's shift to some Cys residuein a more restrictive environment and/or with cross-linking of BSA molecules into polymers..

195

jfiAEICMCDIFIERS AND OPTICAL CHOICE OF FEACTIONATICNREGIMES

K.Prokes' .M.Lokajic 'ek

Oncological Laboratory,Charles Uriv.Prap:ue,c'SSRInstitute of Physics^SAVjPrague^SSR

Frsctionstion treatment courses commonly usedin radiotherapy ere based on the assumption thatnormal tissues recover -in intervals between dosefractions more rapidly than malignant tissues.However,the choice of an actual irradiation schemefor a given tumour starts practically till now fromempirical experience.Some attempts were done todetermine the cumulative effect for different frec-tionations with the help of mathematical models.Ellis concept of the so celled nominel standarddose is commonly known and made use of still in themost rsdiotherapeutical depertcients.Unfortunately,its applicability is strongly limited by some a-priori assumptions which cannot be justified in anyway.A more general concept has been proposed whichbrings the cumulative effect into a close relationto inactivation characteristics of individual cellsand alows a more realistic separation of the roleof proliferation end inactivatdon processes.Somerules concerning the optimization of fractionationschedules in individual cases and being based onthe differences of survival curves of tumour andnormal cells can be derived.An additional way howto enlarge the effect of radiomodifiers in radio-therapy courses by a change of fractionation she-mes has been shown.

196

THE F.ODIFYING ROLE OP OXYGEN IN THE PROCESS OPRADIATION-INDUCED DSB FORMATION

1 . PfilDAL

Radiotherap. dept., University Hospital, OlomoucCzechoslovakia

The shapes .of experimental sedimentation pro-files obtained for cells Saccharomyces cerevisiae211 B irradiated by different doses in anoxic con-ditions and published recently (Frankenberg-Schwa-Cer et al., Int.J.Radiat.Biol. 6., 261) deviate sig-nificantly from the common ones. They can not bereasonably,with tne help of an usual approach,in-terpreted. A more general approach has been proposedand a new model analysis of all the given data ob-tained under aerobic and anoxic conditions has beerperformed* The following conclusions can be drawn:1* There is not a homogeneous distribution of DSBalong all DKA molecules, but at least two fractionswith different radiosensitivities exist in any cell.2, The frequencies of DSB in diverse fractions areinfluenced by oxygen in a different way. The twoDHA fractions seem to correspond to euchromatin andheterochromatin. Thus, the radioBensitivity splitof cell DNA visualized by changing oxygen contentmight provide an effective tool for studying thechanges of chromatin structure and DNA organizationdue to such relevant processes as malignant trans-formation, differentiation, aging and methabolicregulation in eukaryotic cells.

197

POSTIRRADIATIOK RECOVER! OP EOSINOPHILIC GRANULOCYTESYSTEM IM MICE MUTANT AT STEEL LOCOS.

M.S.RATAJCZAK & W.WIKTOR-JEDRZEJCZAK.

Department of Immunology, Postgraduate Medical CenterCKP VAM, 00-909 Warsaw, Poland.

Mutant* at Steel locus posess microenviromentally•ediated defects of henopoiesis associated vitb unusualradiosensitivity (lb*2 Gy). Recently, ve hare found thatin addition to anemia and nast cell deficiency they suf-fer from severe defect of eosinophils. Together, this

pronpted us to study the effect of Steel locus on post-irradiation recovery of absolute eosinophil count in theperipheral blood. It was found that in normal nice thiscount exhibits essentially different pattern of recoverycoapared to the counts of other blood cells and returnstonoraal not earlier than 40 days postirradiation (1 Gy)while in Sl/Sl adce such recovery is delayed to around60 days postirradiation. For comparison reticulocyte,neutropbil and platelet counts returned to normal valuesbetween 10-20 days postirradiation in control mice andbetween 20 and 30 days in Steel mice. This may suggestthat different cells are responsible for production ofeosinophils than those responsible for supplying erytro-cytes, neutrophils and platelets and that their functionis severely affected by defects produced by mutationsat Steel locus.

198

CERTAIN PATTERNS OF DNA DOUBLE-STRAND 3REAKS INMEMBRANE ATTACHED SUPERSTRUCTURE UNITS CAUSE CELLINACTIVATION

K. REGEL

Central Institute of Nuclear Research,13051 Dresden, PF 19, DDR

The discovery of the arrangement of the chromoso-mal DNA in membrane attached superstructure units(MASGUs) seems to be the key for the understandingof the action of ionizing radiations on mammaliancells.Concerning spar9&ly ionizing radiation the follo-wing hypothesis is proved successfully in thispaper: The appearance of k^2 double-strand breaks(DSBs) in any MASSU of a Gj cell, respectively, ineach MASSU of any sister-MASSU pair in a late Scell leads to their inactivation. DSB patternscharacterized by less DSBs will be repaired by therecombination with the homologous MA3UU (Ci cell},respectively, by the interference of the recombina-tion repair of DSBs, sister chromatid exchange, andDNA degradation (S cells). The dependence of theform and steepness of the dose survival curves onthe cell cycle stage can be explained by thisradiation action mechanism, if changes of thecompactness and of the replication condition of theMASGUs and the division state of the attachmentpoint(s) of the sister-MASSUs are taken intoaccount.besides the radiation action model interprets theobserved changes of the dose survival curves ofasynchronous cells in dependence on the stoppingpower of the radiation as well as on the dose rateand the fractionation.

199

SCANNING ELECTRON MICROSCOPY OF THE IRRADIATED MOUSEBLADDER UROTHELIUMJ.B.REITAN and K.FEREN

National Institute of Radiation Hygiene and NorskHydros Institute for Cancer Research/ Oslo, Norway

Hairless mice were irradiated with 0, 10 and 20 Gyto the bladders. 1 year afterwards the urothelium wasinvestigated with scanning electron microscopy (SEM)and cell kinetic methods.

Significant changes were only seen in the 20 Gyirradiated bladders.The normal polyploid cell popu-lation had changed ta a diploid state with no in-crease in proliferation parameters. SEM showed markedsurface alterations varying from area to area withinand between the bladders.The cover cells had mostlyretained their polygonal shape,but the cells had lostmost of their normal surface features.Even in wellstretched specimens were areas with a cobblestone orfuzzy appearance bulging into the bladder lumen andexhibiting a wide variance of surface structures.Manyof the cells showed numerous blebs and large globularprotrusions lacking surface structures and bulginginto the lumen.

The irradiation must have interfered with the nor-mal cover cell differentiation and building up ofpolyploidy.Featureless cover cells have been attri-buted to effect of urine but has mainly been foundin irradiated urothelium and in urocarcinogenesis.(Newman t Hicks,1981,SEM 1981/111,1. Hodges,1973,SEM1973/111,589) The cobblestone and fuzzy appearancesuggests focal hyperplasia which has not been parale-lled in kinetic parameters. Antonakopoulos (1982,B JCancer 46,403) found focal hyperplasia and cancer inIrradiated rat urothelium. Thus the presented SEMChanges are probably preneoplastic in nature and notonly late nonstochastic effects as a result of com-pensatory proliferation.

200

RELATIONSHIP BETWEEN LIPOLYSIS AND LIP0FUSCI1T-

LIKE PIGMENTS FORMATION IN ADIPOSE TISSUE AFTER

WHOLE-BODY GAMMA IRRADIATION OP RATS

?•?. Re.jholcova, J, '.'/ilhelm

Faculty of Medicine, Charles University,

Prague, CSSR

The lipolysis (determined as a glycerol release

by chemiluminiacent assay) was studied in relation

to oxidetive deterioration of lipida that was ex-

pressed as a concentration of lipofuscin-like pig-

ments(LFP). The LFP were determined fluorimetrica-

lly in the epididymal fat of rats irradiated by the

LD(-0 dose of Co. The samples for the estimation

of basal and noradrenaline stimulated lipolysis

as well as for the LFP concentration were taken

after 6 h, and on the 3rd, 7th, 13th, 20th, and

23th post-irradiation days. The values of the lipo-

lysis and LFP in the irradiated rats were close to

controls until the 13th day but then both values

started to grow simultaneously. Suchjan increase in

the LFP might be due to more intensive lipolysis

in which the fatty acids come to a eloaer contact

with oxygen that leads to their oxidative damage

and subsequent LFP formation.

201

GASTROINTESTINAL RADIATION INJURY OF SUPRALETHALSINGLE GAMMA-IRRADIATED DOGS: A MORPHOLOGIC OBSER-VATIONM. RESL. M. DOSTJLPurkyni Medical Research Institute, Hradec Kralovtf,Csechoelovakia

The morphologic change* of digestive tract insix whole-body irradiated doga with the doses of 30,50 or 200 Gy were described* The source: 12,321 TBq60 Co, the doae rate 1,1 Gy.s-1 in the place of bodycentre (tr»» apace). The tissue samplea during au-topay after ante finem killing were removed. Thatis J2 and 96 hours after 30 Gy, 61 and 62 hours af-ter 50 Gy, 13 end 22 hours after 200 Gy. The typicalintestine syndrome of acute radiation sickness waaobeerved following lower doses, especially after 30Gy. Microscopic changes were characterised by col-laps of villi with a local necroaea of thier tips,by congestion, focal heaorrhagiea and destructionof lymphoid tissue. The dilatation of crypt s glandswith flattened or monstrous single and multinuclea-ted cells WAS found. These elements locally reachup to tips of villi and can be interpreted as a re-sult of an injured repair-capacity in irradiatedintestine. The absence of typical granulocyticcells reaction following 30 Oy may be explained bya longer survival-time aufficient for the destruc-tion of leucocytes during progressive bone marrowcell a depression. No perforation of intestinalwall was found.

202

EFFECTS OF LOW DOSES OF GAMMA IRRADIATION ON THE EXTRACELLULAROXYGEN CONSUMPTION OF WI38 LUNG FIBROBLASTS

B. Reubel, F. SteinhauslerAbteilung fur Biophysik, Universitat Salzburg, 6'sterreich

Quantitative oxygen consumption of WI38 embryonic lung fi-broblasts was measured by an experimental set-up of a chemicalmicrosensor and polarographic oxygen electrodes. Cell suspen-sions of WI38 cells varying in its concentration from 0.06 -1.13 x 10" cells/ml were irradiated with a Co-60-source and do-ses from 1mGy - 8.5 Gy (dose rate: 6.5-7 Gy/hr).The oxygen consumption of WI38 cells after irradiation showedtwo different mean types of reaction: decrease and increase ascompared to the values of the control group. The occurrence ofeach of these effects is correlated with the dose and/or thecell concentration-Independent of the above cell concentration the cells decele-rated their respiration rate after irradiation with doses of1ntGy - 350 mGy. This effect points to a possible slow down ofthe cell metabolism after irradiation with low doses.An acceleration of the oxygen consumption can be found afterirradiation with doses from Q-35 - 8.5 Gy at cells in. concen-trations of 0.16 - 0.7*1 x 10° cells/ml; thereby increasing cellconcentrations can be irradiated with increasing doses in orderto produce the same effect. The metabolic rate of WI38 cellsseems to be accelerated by the consumption of energy for in-duced repair.

203

Na-succinatc. as a protective compound against

lipid peroxidation and acut 60-Go-gamma irradiation

&. Ronai, L. Tretter* L. Keszaros* Gy. Benko,I. Horvath ;"F.J.C." NatLRes.Inst. for Rsdiobiol . and Radiohyg.Budapest, HUN.II. lost, of Biochem. Semmelweis Univ. Med. L>ch.

Budapest, HUN.

Messaros et.al. have observed, that a respiratorysubstrate, succinate inhibits NADPH-dependent (ADP-Pe stimulated) lipid peroxidation of liver mito-chomdria. It was found, that this effect of succi-mattdecreased after 12h whole-body 60-Co-gamma-irradiation depending on the dose of irradiation.I» the present experiments the inhibitory effect

oX succinateon lipid peroxidation was investigatedlm liver mitochondria, prepared from irradiatedrats with 9,0Gy. Lipid peroxidation was assesed bythe measurement of malondialdehyde (liDA) applyingthe thiobarbituric assay.9»0Gy 60-Co-gamma-irradiation results in increasedMDA comcentrations in liver mitochondria, duringthe first four days after irradiation, but theinhibitory effect of succinatewas significantlyAiaimiahed. The rate of lipid peroxidation remainedmehamged 7 and 10 days after irradiation.?h«»e observations indicate that the inhibition oflipid peroxidation by suecinate may play an impor-tamt role im the defense against irradiation.

204

USE OF MICROWAVES FOR MODIFICATION OF RADIATIONDAMAGE IN MICED. ROTKOVSKA. A. VACEK, A. BARTONlCKOVAInstitute of Biophysics, Czech. Acad. Sci., Brno,Czechoslovakia

Combined irradiation of mice (CBA x C57Bl)Fiwith gamma rays and microwaves (2450 MHz, CW, 100mW/cm2) decreases the lethal effects of gamma rays.Increased resistance of mice to ionizing radiationwas observed at their treatment with microwaves30 min after gamma irradiation and also after ashort-term treatment of the mice with microwaves14 days prior to gamma irradiation. The microwavesraised the proliferation capacity of the hemopoi-etic stem cells (CFU8) and also* their seeding rate(f-factor). These changes in heraopoietic stem cellsirradiated with microwaves in situ had a favourableeffect on the couree of recovery of the radiationdamage of the hemopoiesis devastated by ionizingradiation and reduced its lethal effects. The samemodification of CFU8 occurred after microwave irra-diation of a bone marrow suspension. Evidence wassupplied for the participation of beta adrenergicreceptors in the mechanism of increased prolifera-tion and CFU8 seeding rate after microwave irradia-tion. The therapeutic efficiency of the bone marrowin the treatment of radiation disease in mice washigher when it was microwave-irradiated than uponapplication of the same amount of bone marrow fremintact animals.

205

TEMPERATURE KINETICS OF THE REPLICATIVE AND UN-SCHEDULED DNA SYNTHESIS: ESTIMATION OF Q l 0 AND E a c t

E. ROTREKLOVA. L. BENES


Studies of the dependence of DNA synthesis ontemperature give some insight into the physico--chemical mechanism of Intracellular DNA synthesis.They allow to determine the Q10 value and the acti-vation energy (Eact). The Q10 value gives the ratioof the rate of DNA synthesis at a given temperatureto the rate at a temperature by 10° lower. HereEact expresses the energy (kO) demanded for molethymidine incorporation into DNA. The relativerates of replicative and unscheduled DNA syntheseswere determined over a temperature range of 2° to42 °C in LS/BL, LAs and LC3 cells. The rates weredetermined by measuring the amount of 3H-dTh in-corporated into DNA during 60 ain incubation ofcells at a given temperature. Acid-resistant 3H--acflvity incorporated into DNA at 2 °C was evalu-ated as evidence of DNA turnover, not non-specificadsorption of 3H-dTh. The relative rates of RDS andUDS were expressed as functions of temperature, andfrom these data the values of Q10 and Eact neces-sary for incorporation of one mole of dTh into DNAduring RDS and UDS were calculated. The values ofQ10 and Eact are comparable to those reported forHeLa, V-79, L5/78Y and the epithelial cells. Theexperimentally determined values of Q1O and Eactfor UDS in the lines tested did not vary. UDS com-pared to RDS, is evaluated as a process with lesserdemands on energy*

206

S CHANGES AFTER 60Co IRRADIATON

•>. Rozsival , J« Obenberger2, J,

1 - Department of Ophthalmology, Charles University

Hradec Kralove"

2 - Institute of experimental medicine, Prague,Czechoslovakia.

The authors refer about changes in the transportmechanisms of the lens, its weight, water and dryresidue contents after ° Co irradiation. Adultrabbit of grey chinchila strain were used in theexperiments. One single dose of 10 or 20 Gy wasreached at 50 cm distance from the source after 3or 6 minutes. The weight of the lens markedlyincreased after a dose of 20 Gy in the 12th weekafter irradiation and reached maximum 16 weeks whenlens opacity began to appear. The increased watercontent is responsible for the increased lensweight. A decrease in dry residue content occuredalready before the development of visible lensopacity. The lens ability to accumulate activelyrubidium was disturbed from the 8th week afterirradiation, about 8 weeks sooner than the increaseof weight and water content in lens became manifest.

207

MUTAGENIC EFFECT ON MOUSE SOMATIC CELLS FROMSINGLE OR COMBINED EXPOSURE TO RADIATION ANDCXCLOPHOSPHAMIDEI. RUPOVA, D. BENOVAInstitute of Roentgenology and Radiobiology,Sofia, Bulgaria

The mutagenic effect produced on bone marrowcells by single administration of 20 mg/kg b. wt.to mice was studied at the following post-treat-ment times: 6t 12, 24, 36, 48, and 60 hours. Thetime of peak aberration yields was found to be12-24 hours (10.9% and 9»t% aberrant cells, res-pectively).

The response to a single 3-Gy gamma-ray expo-sure was examined 6, 12, and 24 hours later. Da-mage to genetic structures was maximum at 12hours postradiation (81.9% aberrant cells).

Combined treatments with both agents took intoaccount the times when effectiveness was observedto be highest after single exposures to cyclophos-phamide and radiation. The combined treatments,given simultaneously or 12 hours apart, resultedin aggravation of genetic lesions, as indicatedby aberration yields per cell of 312.9% and 263%,respectively.

208

LONGTERM EFFECU OF OCCUPATIONAL EXPOSURES TOIONIZING RADIATIONM.RUZPICInstitute of Hygiene and Radiological Health MedicalSchool, Sarajevo

The object of the study wos to establish wether the-re wos any positive correlation between the cumula -tive doses of Ionizing radiation of occuptionallyexposed workers and the rate of binuclear lymphocy-tes 1n their blood samples.A survey of cumulative doses of 1335 workers in Bos-nia and Hercegovina exposed to ionizing radiationbetween one and twentyone years wos made on the ba-sis of the documentation of the Institute's laborato-ry for filmdosimetry. The range of cumulative doseswos from 0,27 mSv up to 59,01 mSv. 85% of workes hadcumulative doses below 10 ntSv.

In the course of 1984 the blood samples of 531 ofoccupationally exposed persons were taken and analy-sed for binuclear lymphocytes In native samples.The percentages of subjects with chromosome aberati-ons 1n groups divided by cumulative doses In mSv,ranged between 11,1 to 45,4 percent.The averages of rates of binuciears per 10.000lymphocytes ranged between 0,2 and 0,65.No positive correlation between the cumulative doseand the rate of binuclear lymphocytes wos found.

209

SURVIVAL OF D. RADIOPROTEOLYTICUS AND E. COLI Hfr HFOLLOWING HYDROGEN PEROXIDE APPLICATION

L. RYZNAR. V. DRA~glL

Institute of Biophysics, Czechoslovak Academyof Sciences,

Brno, CSSR

Increased attention has recently been paid toa study of the mechanisms of the effect of hydrogenperoxide on cells. The fact that under certain condi-tions hydrogen peroxide concentration in the cell mayincrease indicates the necessity of studying this me-chanism. This work compares the effect of hydrogenperoxide on the highly radioresistant bacterium Deino-coccus (Micrococcus) radioproteolyticus and on the ra-diosensitive bacterium E. coli Hfr H. While underthe effect of ionizing radiation D. radioproteolyticusexhibits a 6-8 times higher Do value than E. coliHfr H, the difference in sensitivity is much lowerwhen both microorganisms are treated with hydrogenperoxide. A comparison of the spatial distribution ofradicals arising on irradiation of cells with ionizingradiation and the distribution of OH radicals derivedfrom hydrogen peroxide indicates that the damagecaused by H2O2 includes considerably less of thosetypes arising from multiple effects of radicals onthe same DNA site, i.e. relatively more poorly repa-rable damage. The conclusion is drawn that the smallerdifference in sensitivity to H202 between the twomicroorganisms is caused by increased reparabilityof DNA changes in E. coli Hfr H rather than by de-creased reparability of DNA damage in D. radioproteo-lyticus .

210

'RADIOBIOLOGICAL PROPERTIES OF THE QUATERNARY STRUCTUREOF CELLULAR DNA1

S.A. Sabovljev, A.M. George and W.A. Cramp,MRC, Radiobiology Unit, Hammersmith Hospital.G. Harris, Kennedy Institute of Rheumatology, Hammersmith.M. Hedges and S. Hornsey, MRC, Cyclotron Unit, HammersmithHospital.

On challenge with 2M NaCI the nuclei of human lymphocytesyield aggregated DNA. The buoyancy of the DNA nuclearmaterial in 5-20% sucrose is greater when immediately isolatedfrom irradiated cells than when isolated from unirradiatedcells. The buoyancy returns to unirradiated levels if cellsare allowed time at 37°C in nutrient conditions. An o.e.r. forthe initial effect - increase in buoyancy - is between 2 and 3.Return to unirradiated buoyancy levels is complete at low dosesafter 60 min at 37°C. DNA material from cells derived frompatients who have exhibited hypersensitivity to radiotherapyexhibits greater increase in buoyancy and slower repaircharacteristics than DNA material from the average normal sub-ject. Misonidazole at 4mM in anoxic conditions increases theeffect of radiation induced buoyancy by a factor of three.Both chemical modifiers also reduced the rate of repair.Neutrons are more effective than X-rays in producing buoyancychanges by a factor of 3-4 and repair is much slower. Thesechanges observed in the property of the DNA material fromlymphocytes suggest that alteration in the configuration ofsuch material by the loss and re-establishment of relativelyweak bonds are closely related to the well known changesobserved in classical cell survival experiments with cells inculture. Where the proliferation of human lymphocytes hasbeen observed by concanavalin A stimulation oer, RBE andchemical sensitisation has been of the same order as themeasured buoyancy changes.

211

SUBCELLULAR DISTRIBUTION OP PH]-FLUOMETHUROK

Iff RATS ORGANS.

SAGATOVA G.A., MIRAKHMEDOV A.K.

Institute of biochemistry, of Academy of Science

of Uzbek SSR,Tashkent,USSR.

The use of labelled pesticides allow to re-

veal their predominant localization and sequen-

ce of biochemical distribution of PH]-fluome-

thuron in the organs of rats were studied.Maxi-

mal label is registrated within 40-80 min.after

administration of isotope.lt was established,

that the largest content of labelled fluomethu-

ron was present in the liver and the smallest

one-in the brain.Subcellular distribution of

fHJ-fluomethuron in these organs indicated that

pesticide was predominantly localized in micro-

somal fraction.Distribution of pesticide in

intracellular structures,its metabolism and de-

toxication depends on its effect on membrane

permeability.The degree of penetration of pes-

ticide depends on lipid and protein environment

of the cell.

212

SPECIFICITY OF THE LUNG DAMAGE AFTER COMBINED APPLI-

CATION OF FORMALDEHYDE AND EXTERNAL IONIZING RADIATION

P.Salovski, H.Nechev, V Shopova, Ts.Shopova

Higher Medical Institute, Pleven, Bulgaria

Changes in the lungs of rate poisoned through in-

halation of formaldehyde in the course of 8 days, 4

hours daily, at a concentration of 70 mg/m were stu-

died. Immediately after treatment, the animals were

given a single ionizing radiation of .4 Gy. Increased

activity of the following enzymes is found: lactate

dehydrogenase (LDH), alkaline and acid phosphataee

and the contents of common protein in the bronchoal-

veolar lavage liquid in the groups treated separate-

ly with formaldehyde and combination with 4 Gy. The

activity of LDH and glucose 6-phosphate dehydrogenase

in lung homogenate is also increased. The content of

malonic dialdehyde and SH-groups and the activity of

superoxiddismutase show an increased lipid peroxida-"-

tion after the 5 day. Towards the 30 day the con-

tents of oxyproline in serum and homogenate are in-

creased. Formaldehyde and the combination with 4 Gy

cause a swelling, an alveoler collapse and lymphoid

infiltrations. There is evidence of a potentiation of

the biological effect.

213DOES BSO AFFECT CELL RADIOSENSITIVITY ONLY BYREDUCING GSH CONTENT?

0. Sapora, J. C. M. Bremneř, V. Capuano, B. R.Guerra, A» Maggi and G. Simoně. - Istituto Superioredi Sanita', ENEA, aňď Consiglio Nazionale delleRicerche/ Roma and Bologna, Italy.

V79 cells treated with 1(T3 M BSO for 18 hrs.exhibit increase in radiosensitivity with regard toboth lethal effect of radiation (ER 1.3) andradiation induced mutability (ER 1.4). Thecorrelation between survival and mutation frequencyis linear, as in control conditions, but moremutants are produced for any given survival level.The effect on cell survival corifirms that obtainedby Mitchell et al. (1983, Radiat. Res. J96, 422) onthe same cells, while that on GSH level issignificantly lower. Perhaps this is due to thedifferences in culture media. - The data suggestthat the effects on radiosensitivity may not bestrictly related to cellular GSH level, confirmingprevious observations, on E.coli and CHO cells,showing that BSO treatments not affecting GSH levelcould modify radiosensitivity of either parentallines or of some radiosensitive mutant. - Recentobservations on E. coli show that the GSH content ofcells grown in synthetic medium containingcasaminoacids is 'about 5 times lower than that ofcells grown in the same medium with only essentialamino acids. Moreover, while in the formercondition BSO is practically not affecting GSHlevel, in the latter it does. - It appears thatmetabolic alterations produced by BSO may affectradiosensitivity independently of GSH level.

214

THE INFLUENCE OF OXYGEN ON THE INDUCTION OF RADIATION DAMAGEIN DNA IN MAMMALIAN CELLS AFTER SENSITIZATION WITH DEM AND 8S0G.P. VAN PER SCHANS, 0. VOS*. W.S.D. ROOS-VERHEIJ and P.H.M.LOHMANTNO Medical Bio logical Laboratory, R i j s w i j k , Netherlands,

'Department of Cel lb ic iogy and Genetics, Erasmus Univers i ty ,Rotterdam, Netherlands.

Treatment o f mammalian ce l l s w i th BSO (buthionine sulphox-imine) and DEM (d ie thy l maleate) resu l ts in a reduction of thei n t r a c e l l u l a r GSH (g lutath ione) and NPSH (non protein-boundSH) leve ls . The e f f ec t o f deplet ion of GSH and NPSH on radio-s e n s i t i v i t y was studied i n re la t i on to the concentration o foxygen during i r r a d i a t i o n . Single- and double-strand DNAbreaks {ssb and dsb) and c e l l k i l l i n g were used as c r i t e r i afo r rad ia t ion damage. Furthermore, repai r o f ssb and dsb wasfollowed in the f i r s t 30 and 120 min a f t e r rad ia t i on . Inaerobic condi t ion BSO and DEM treatment gave a small s e n s i t i -zation (10-20%) fo r the 3 types o f rad ia t ion damage (ssb, dsband ce l l k i l l i n g ) . Also under st rongly hypoxic condit ions(0.01 |iM oxygen i n medium) the sens i t i z ing e f f e c t of bothcompounds on the induct ion of ssb and dsb was smal l . Atsomewhat higher concentrations of oxygen (0.5-10 yM) however,the sens i t i za t ion on the induct ion of ssb and dsb was muchstronger (up to about 100%). This suggests tha t SH-compoundsin the c e l l p ro tect mainly against 0-type damage e i the r bychemical recons t i tu t ion of radica ls on DNA or by preventionof f i x a t i o n by oxygen of ion izat ions on DNA. In general,BSO and DEM treatment d id not s i g n i f i c a n t l y a f f ec t therepair o f ssb and dsb.

215METABOLISM OF VITAMIN B AND RADIATION EFFECTW. SCHMIDT, K. WULFF, U. GRIMM, A. KEINKEGreifswald, GDR

Radiation induced: efficiency of active agents ofthe vitamin B complex on the one hand and co-enzymfunction of the intermediary metabolism with repairon the other hand justify the statement, that in thecourse of the acute radiation disease much importantshould be attributed to the vitamin B balance fromthe diagnostic, pathophysiologic and therapeuticpoint of view. The repair supporting effect in thesemi- and sublethal dosage range proved by us wereported on the Annual Meetings of the European So-ciety for Radiation Biology 1968 in Interlaken and1969 in Ulm. From the pethophysiological point ofview these investigations find their continuationfor many years by means of modern enzymatic methodsin animal experiments and clinics. On the base ofthe established TPP effect impairment of the vita-min B, supply could not be found. In contrast tothis it comes to significant deviations concerningboth FAD and TLT effects that point to a B» and Bgdeficiency.. The results are suggestive of radiationcaused disturbances of vitamin B 2 metabolism andtumour caused disturbances of vitamin Bg metabolism*The investigation results show at once, that bothdisturbance*! can be successfully influenced' by aprophylactic vit&min B complex treatment*

216

RADIOCHROMIC DETECTORS AS DOSIMETER AND MODEL SYSTEMFOR BIOLOGICAL HIGH LET RADIATION EXPERIMENTSE.SCHNEIDER, J.KIEFER, K.J.WEBER

Strahlenzentrum der Justus-Liebig-Universitat,Giessen, FRG

A nylon-base dye film (FWT-60, Far West TechnologyGoleta, USA) was exposed to protons a-particles, Ne-,Fe-, Kr-, Xe- and U-ions of different energies. Theresponse was measured as changes in optical densityin the maximum of the absorption at 600 run. In a widerange (2-3 decades) the optical density depends line-arely on the particle fluence; with high fluences thesystem is saturated. The energy transfer and the trackstructure of the particles are essentially responsiblefor the reaction of the system: the optical densityincreases with increasing linear energy transfer. Across section for a certain effect level is calculatedfrom the response characteristic. This cross sectiondepends linearly on Z*2/3Z for particles from protonsto uranium ions, indicating that the system reacts asa single hit detector. The inhibition of ribosomalRNA synthesis in yeast cells which was earlier mea-sured over a wide range of accelerated particlesexhibits the same dependency on Z*2/82 as the dye film.The inactivation cross section also linearly dependson Z*a/32.

217

STUDY OF itfR-2721 HI EATS ,/ITH DIPFJSEHJNT TYPES OFBXPERlMiNTAL ULCERgjSCHJJBITZBR, GyjBiiKKOF.J.-Curie National Research Institute for Radio-biology and Radiohygiene

Among radioprotective compounds developedduring the past 15 years, the most perspectiveproduct is the WH-2721 derived from the"classic"radioprotective molecule of cysteamine'.

Since the duodenal ulcer'induced by cyfcteamineis one of the characteristic types of experimentalulcer, we have found interesting to study whatchanges occur in animals on the effect of WR-2721".According to our experience,the radioprotectivedose of WR-2721 produced no ulcerativ lesions inthe stomach of the rat 24 hours after intramuscu-lar or intraperitoneal administration.

Further we have investigated the effect ofWR-2721 on experimental ulcer of different patho-genesis /Shay-ulcer, reserpin-ulcer/.It has been found that the given drug - in contrastto other radioprotective compounds - has a dosedepending inhibiting effect both on the Shay- andreserpine-ulcer, but has a dose depending duodenalulcerogen effect'.

218INTERPRETATION OF CELL SURVIVAL CURVES WITH MICRO-DOSIMETRYA. SEDLAKInstitute of Hygiene and Epidemiology, Prague,CSSR

Analysis of cell survival curves can be clearerin those cases where along with the microdosimetricconcept also application of the LET concept isjustified* In the straight - line approximation isthen possible to express explicitly the distribu-tion function of specific energy and by includingof further biophysical aspects the courses of dose- effect curves can be deduced. The results of theanalysis are verified by means of experimental sur-vival curves.

219

THE ROLE OF LIPIOS IN BONE MARROW AND THYMUS OF

IRRADIATED RATS

A. SEDLA'KOVA'. 3. TIMKO

Department of General Biology, Faculty of Sciences,

P.O. SafaVik University, KoSice, CSSR

Changes in lipid synthesis from U- C-glucose,

H20 and 1,2- C-acetate in bone marrow and thymus

of rats irradiated with a single dose rate of 14.4

Gy and 6.0 Gy of X-rays and of rats irradiated con-

tinuously with a daily dose rate of 0.6 Gy for 120

days and with a daily dose rate of 0.1 Gy of gamma

rays for 150 days was investigated. The stimulation

of lipid synthesis accompanied by a triacylglycerol

(TG) accumulation was found in all studied models.

In bone marrow of rats irradiated with a single

doee rate of 0.6 Gy the tendency to repair occured

before the 28th day and in the thymus the recove-

ring occured on day 7 after irradiation. The lipid

synthesis and TG concentration in both tissues of

rats irradiated continuously with a daily dose ra-

te of 0.6 Gy were increased during the whole time

and for a daily dose rate of 0.1 Gy changes were

smaller

220

POSTIRRADIATION DIP IN STEM CELL NUMBERS IN MICEPRETREATED WITH CYCLOPHOSPHAMIDE

L. gEFC, M. KRS"EKt E. NEC~AS

Dept. of Pathophysiology, Faculty of General Me-dicine, Charles University, 128 00 Prague 2,Czechoslovakia

Stem cell numbers continue to decrease in the-haematopoietic tissue for 24 hours after acute whc-le body irradiation. This phenomenon, termed thepostirradiation dip, was observed after differentdoses of irradiation by several authors. The stemcell numbers fall to about 50 % of those foundimmediately after irradiation. The C57B1/1O fema-le mice had been given 200 mg per kg b.w. ofggyclo-phospharaide 3 or 7 days before irradiation ( Co;?. Oy). The postirradiation dip W8S then examineduntil 30 hrs after irradiation. The results sho-wed that while in the mice given cyclophosphamide3 days prior to irradiation the postirradiationdip was abrogated ( 2 - 3 fold increasein stem cell numbers), the postirradiation dip wassignificantly enhanced in the mice injected withcyclophosphamide 7 days prior to irradiation (7 -10 fold decrease in stem cell numbers). This workconfirms and extends the observations publishedpreviously (Blackett N.M., Botnick L.E., 1981,Blood Cells, 7, 417) and shows that the effect ofirradiation on the haematopoietic tissue can besignificantly modified by the same treatment ap-Dlied at different times before irradiation.

2 21

THE D0SE-R33P0NSE RELATIONSHIPS IN DIFFERENTCONDITIONS OP RADON DAUGHTER EXPOSURE

J . § E V C : E.KUNZ. L.TOMA*§EK, JiHORA*C"EK, A.SEDLA'K

Institute of Hygiene and Epidemiology, Prague,National Health Institute, Karlovy Vary, CSSR

The analysis of results of the Czechoslovakstudy after on the average thirty years' observa-tion in a group of uranium miners has shown thatthe dose-response relationship and the attribute-able lung cancer risk per WLM appears sensitiveto age at the first exposure, to total accumulatedexposure, to the length of exposure and other typesof time distribution of exposure: the risk wassignificantly higher in older age at first exposureand decreased at high exposures as a consequenceof a simultaneous inhibitory effect of radiation;the highest risk per WIM was in cohorts where atthe same total accumulated exposure the yearlyexposure was higher in the first years and laterdecreased, and in cohorts with the length of expo-sure of more than 10 years. Significant inhibitionof the attributable lung cancer rate in the highercumulative exposure category concerned mainly thesmall cell undifferentiated tomours. The data ofthe epidemlological study were compared with threebiological models permitting prediction forvarious conditions of exposure to radon daughterproducts*

222

LUNG CANCER RISK AT LOW LEVEL OP RADIATION EXPOSURE

J.SEVC, V.PLAC"EK, A.§MfD. L.STROMP

Institute of Hygiene and Epidemiology, Prague,Health Institute of Uranium Industry, Prfbram,

The attributable lung cancer rate in differentepidemioLjîcal studies is variable with total ac-cumulated exposure to radon daughters, but thereappears to be a decrease in risk per unit exposureat high exposures. None of the foreign studies, sofar, has produced data which show a statisticallysignificant excess of lung cancer in the cumulativeexposure category lower than 60 WLM. In four epide-miological studies in CSSR, six groups of minersare followed up at different levels of inhalationexposure. In three studies there has been recentlyproved a statistically significant excess of lungcancer in the cumulative exposure category lowerthan 50 WLM. The attributable annual lung cancerrisk per WLM in the lowest cumulative exposure ca-tegories is significantly higher than the meanattributable risk in the whole study groups}theseobservations are not at variance with the idea ofa considerable decrease or lack of a simultaneousinhibitory effect of radiation at low radiationexposure* The attributable lung cancer risk signi-ficantly increased also with age at irradiation,with the length of observation period and in rela-tion to the time course of exposure accumulation.The results of the epidemiological studies haveshown that at low radiation exposure and/or expo-sure at environmental levels of radon daughters,the attributable lung cancer risk is not decreasedand a certain increase in the attributable riskper WLM, owing to the decrease in the cumulativeexposure, can be expected.

223

RADON DAUGHTER CANCER IN MANJ.§EVC. L.TOMAÊK, V.PLACEK, E.KUNZ, A . S l i f oInstitute of Hygiene and Epidemiology, Prague, CsSRHealth Institute of Uranium Industry, Prfbram, CSSR

The results of a thirty years' observation fol-lowing the mean accumulated exposure of 300 WIM ina group of Czechoslovak uranium miners showed,similarly as in the U.S. and Canadian groups, thatonly the death rate due to lung cancer was signi-ficantly higher, while the death rate due to othermalignant tumours and most of the other causes ofdeath did not differ significantly from that ex-pected. The average time from the onset of exposu-re to the time of death from lung cancer was 19,0- 7,0 years* The first statistically significantexcess of lung cancer in persons entering exposureafter 30 years of age was found as early as in thesixth year after the onset of exposure; the high-est attributable lung cancer rate was in the 22ndyear, and in the 30th year the excess of lungcancer was no longer significant. The mean attri-butable annual lung cancer risk, per WliC in thetotal group was 20 x 10"b year"1 HJT*1* the levelof the attributable risk and the linear dose-effectrelationship were significantly influenced by ageat the onset of risk, the height of accumulatedexposure and the way of accumulation of exposure.A brief summary is given of methodological appro-aches of the Czechoslovak epidemiological studies,and the results are compared with the data ofstudies carried out abroad.

224

LONGTERM SURVIVAL OP CLONOGENIC SURVIVORS FROM RADIATIONEXPERIMENTS

*C. B. SEYMOUR and *°C. MOTHERSILL

*Saint Luke's HoBpital, Rathgar, Dublin 6, Ireland.°fhysics Department, D.I.T., Kevin Street, Dublin 8, Ireland.

While studying the growth and plating efficiency of serialpassages of clonogenic survivors of radiation in both estab-lished (CHO-Kl) and primary (human and sheep thyroid) cells,the authors have noted that the progeny of irradiated cellshave a considerably reduced longterm survival when comparedwith similarly passaged but unirradiated controls. The effectwhich we have termed 'late lethal damage1 (LLD) has beenvaguely eluded to in the radiobiological literature of thesixties but has not been the subject of detailed study. Itis now, however, of critical importance in relation to theunderstanding of quantitative data for in vitro transformationstudies and probably explains the 'bell shaped' dose responsecurve observed both by Hall (personal communication) and theseauthors. The results of experiments and computer modellingto determine the extent and relevance of the phenomenon willbe presented.

225

THIOL PEROXYL RADICALS AND RADIATION INDUCED ENZYME INACTIVATICN

G. SIMONE, J.C.M. BREMNER, M. TAMBA

Institute F.R.A.E. - C.N.R., Bologna, ITALY

B.R. GUERRA and M. QUINTILIANI

Institute T.B.M. - C.N.R., Rome, ITALY

In connection with the role of intracellular thiols in deter

ncining the response of living cells to ionizing radiation, data

will be presented on the formation and chemical reactivity of

thiol peroxyl radicals. Evidence has been produced that various,

but not all, thyil radicals (RS-) react with oxygen at almost

diffusion controlled rate constants, sometimes inducing short

chain reactions. The reaction of RS- radicals with oxygen has

been indirectly demonstrated for cysteine and glutathione in

pulse radiolysis experiments by following the decrease of the

amount of RSSR with increasing oxygen concentration

RS- + RS~ s RSSR~ (1)

RS- + 0 - RSO- (2)

The possibility that reaction (2) can be directly demonstra

ted will be reported for glutathione at pH 5.5.

The intracellular concentration of thiols being in the order of

millimolar, it seems likely that sizable amounts of the respe-

ctive peroxyl radicals are produced in irradiated cells. Their

role in radiation sensitivity should be carefully considered be

cause of the evidence produced, by the present and other au-

thors, that thiol peroxyl radicals inactivate enzymes and bio-

logically active DNA irradiated in solutions. Studies on enzy-

me inactivation carried out by the present authors include YADH,

lysozyme and trypsin.

226

Disorders of repair of DIJA damage induced bygamma-radiation and radiomimetics.

Sinelshchikova T.A.,Lvova G.N., Shonija N.N.General Genetics Institute of Academy of Scien-ces of USSR, Moscow

Repair activity after gamma-irradiation andtreatment with the radiomimetic agent-4-nitroqu-noline-1-oxide (4-NQO) has investigated by twomethods: 1) alkaline elution of cells lysed onthe membrane filter; 2) vaccinia virus reactiva-tion and induced tautagenesis of virus in lympho-cytes and fibroblasts derived from the skin by-opsy. Disorders in the resynthesis of single-strand DNA breaks, reduction of virus reactiva-tion and enhanced mutagenesis of virus were ob-served in lymphocytes of patients with homocys-tenurea after gamma-irradiation. These peculi-arities were maintained during 16 passages incultivated fibroblasts. The inhibition of the re-covery of the DNA damage induced by 4-NQO wasdemonstrated in cultivated lymphocytes. Hostcell reactivation of virus was decreased and thelevel of induced mutagenesis was enhanced.

227

A CONSIDERATION OP THE HOLE OF VASCULARITY IN RES-PONSE OF TUMORS TO RADIOSENSITIZERSSIRACKA. E.. REVfcSZ, L.Cancer Research Institute, Bratislava, fiSSRDepartment of Tumor Biology, Karolinska Institute,Stockholm, Sweden

Despite encouraging results with radioaensitizersin experimental system clinical studies have notprovided convincing evidence for effective use ofthis modality in cancer treatment* The discrepancymay be related to a) limited drug dose due to neu-rotoxic side effects, b) negligeable amount of hy-poxic cells and their rapid reoxygenation^ c) in-adequate radiation and/or drug dose fractionation,d) tumor-to-tumor variability of oxygenation.Morphometric analysis of the tissue composition

in uterine cervix cancer used as a model for deter-mination of the vascularity has shown intra- andinter-tumoral variations in vascular density. Cal-culations simulating the sensitizing effect suggestthat an indiscriminate use of radiosensitizers maybe not be profitable. On the assumption that hypo-xic cell sensitizers improve the survival rate sele-ctively in cases with poorly vascularized tumors,categorization of tumors permitting selection ofappropriate cases for combined treatment is urgent-ly needed. Additional methodological work is sug-gested with the purpose of refining existing tech-niques and eventually developing a routine procedu-re for a better characterization of the tumor vaacu-larity.

228

STUDIES OF FIRMLY BOUND DNA-PROTEIN COMPLEXES INIRRADIATED MAMMALIAN CELLS

N.P.Sirota & A.I.Gaziev

Institute of Biophysics, Academy of Science of theU.S.S.R. SU-142292, Pushchino, Moscow Region, USSR

Nuclear protein matrix (NM) takes part in rep-

lication, transcription and compactization of euca-

ryotic chromosomes. DNA-protein complexes (DPC) of

NM and bulk DNA from Ehrlich ascites cells (EAC)

were determined after UV-irradiation (254 nm) and

/-irradiation (60Co). EAC were labelled with 3H-thy-

midine and "^S-methyonine. DPC were obtained by

chromatography on Sepharose 2B CL and HAP columns.

DPC were stable in the presence of 8 M urea and

0.1% SDS. The proteins released after DNA hydrolya-

is were separated by polyacrylamid gel electrophore-

sis. Additional DPC did not form in EAC irradiated

with low and moderate doses, but they were obta? d

after the irradiation of cells with super-lethe

doses. UV-irradiation doses which inhibit DNA s

thesis by 30-50% give rise to DPC of NM, but not of

the bulk DNA. Post-irradiated incubation of EAC

does not decrease the number of DPC number in NM.

229

POTENTIATION OF RADIATION DAMAGE TO DNA AND CHROMA-TIN IN THE PRESENCE OF 1,1O-PHENANTHROLINE - COPPERCOMPLEX

M.SKALKA, M.CEDKOVA


The irradiation of chromatin in aqueous solutionas well as the action of hydrogen peroxide on chro-matin cause a random cleavage of ONA without anyregard to the nucleosomal arrangement of chromatin.On the other hand, some agents, like phenanthroline/bleomycin a.o., are able to bind preferentially tothe spacer ONA segments; under suitable conditions(i.e. in the presence of SH-compounds and oxygen orperoxide) they generate free radicals in the imme-diate proximity-to the DNA chain and cleave chroma-tin to nucleosomal particlea ( DNA spacer-specificaction). Our further experiments showed that theeffect of irradiation on DNA or chromatin is poten-tiated in the presence of phenanthroline, and thecleavage in chromatin is conveyed to the spacer seg-ments. Phenanthroline probably makes use of the wa-ter radiolysis products for the generation of fur-ther free radicals in the proximity to the spacerDNA. To our knowledge, such possibility of potentio-tion of radiation damage by the presence of a radi-cal-producing system has not been considered yet.We focus our present experiments on the question ofwhether a similar potentiation could be achievedalso>by the presence of bleomycin, a potent cancert-static drug, which is also known to damage DNA bygenerating free radicals.

230

COMPARISON OF RADIOPROTECTIVITY OF SOME SUBSTANCESIN CHICKENSI.SKARDOVA, K.FRIED. B

Department ef Internal Diseases I,, Department ofPath*logical Morphology, KoSice, CSSR

Chang*« in th« aain indices ef efficiency,the clinical, heaatological and pathemorphologicalpicture were examined ia fattening chicks at 48days of age. The birds were dirided into 5 groupsper 20 birds including the controls. They were lo-cated in special cages in groups of 10 birds.Fodder and water were given ad iibitua* 60 chickenswere exposed of irradiation from a Co sourcea total of 15 days at 1.9 Gy per day. Two groupsreceived radioprotective substances prior to irra-diation /10 % Cardilan and Roboran H/ for 10 days.Examinations were Bade after various cumulated do-ses from 1.9 Gy to 28.6 Gy at 13.tine intervals.After 10 days of application of radioprotectivesubstances woight of the birds increased. After thecumulated dosis of 13.3 to 26.7 Gy the lowest liveweight and feed consumption was observed in thegroup receiving no radieprotectiv* substances. Theabsolute lethal dosis in this group was 26.7 Gy; inboth groups with radioprotection this value was28.7 Gy. Loss of lyaphoid cells and Multiplicationof reticuloendothelial fibres were found in thespleen. In the bone aarrew complete loss of haeao*poetic eleaents was observed. The results indicatedat haeaorrhagic diathesis characterized by pancyto-penic phthisis.

231THE PROTECTIVE EFFECT OF MELANINS AGAINST THE UV-INDUCED DEGRADATION OF METALLO-PORPHYRINS

J.S&AWINSKI*. L. CIESLA and D. SiAWINSKA

institute of Physics Higher Education School, CracowDepartment of Physics Agricultural Academy, Poznaii,PRL

High doses of the UV-B radiation absorbed by solu-tions of metallo-porphyrins(MP) cause their degrada-tion. Aerated aqueous solutions of biologically impo-rtant MP: cytochrome c, hemoglobin and chlorophyll ain concentrations 0.01-1 mM were irradiated with theUV-radiation flux of 1O19 quanta/s.dni3 (E=5.5 eV)withand without 0.01-0.001^ of melanin in a flow system.The rate of MP degradation was measured by the:1/ changes of the characteristic absorption (Soret,o(,ft)and fluorescence (682 nm for Chi a) maxima employedas the intrinsic probes of UP, 2/ the value of theabsorbed UV-radiation dose vs the rate and degrada-tion degree of MP, 3/ intensity of the UV-inducedchemiluminescence resulting from secondary peroxyra-dicals, and A/' use of standard radical scavengers.

It was found that the degradation of MP is mainlydue(>80£) to peroxyradical reactions with a minorinvolvement of (02)2 1Ag1Ag dimols. The presence oflow concentrations of melanins diminishes the rate ofMP degradation by the factor of 5-15. The protectiveeffect ia equal or higher than that of the most potentradical scavengers and antioxidants. Resonance energyand energy of higher occupied and lower vacant molecu-lar orbitals of a model subunit of melanin (dimer ofindoloquinone) correlate with the protective proper-ties of melanins against deleterious effects of UV-radiation.

232

OCCURENCE OF ALKALI-LABILE SITES IN PULSE LABELLEDDNA OF E. col i AFTER THE ACTION OF DNA DAMAGINGCHEMICALS

Vt SlezaYikova and M. Sedliakova

Cancer Research Ins t i tu te , Slovak Academy of Scien-ces, Bratislava, CSSR.

As we have recently shown (Slez^rikova V. andSedliakova M. , 1982, FEBS L e t t . , 148. 251) DNApulse labelled after UV irradiat ion contains alka-l i - l a b i l e s i tes. Now we have t r ied to learn whetherchemical agents damaging DNA molecules or interrup-ting DNA replication w i l l also i n i t i a t e productionof a lka l i - l ab i l e sites in the newly synthesizedDNA. Therefore we have tested three types of suchagents, namely: N-methyl-N-nitrosourea, acting asalkylating agent, nal idixic acid, inhibit ing DNAreplication through the inhibit ion of DNA gyraseand mitomycin C, producing DNA cross-links. In ourconditions the most frequent production of a l k a l i -- lab i le sites was observed af ter the N-methyl-N--nitrosourea treatment and a less frequent produc-tion after the mitomycin C treatment. No a l k a l i -- l ab i le sites were observed af ter the nal idixicacid treatment. Our results seem to indicate thatthe damage to DNA molecules rather than the in ter -ruption of DNA replication is involved in the pro-duction of a l k a l i - l a b i l e s i tes .

233

FEEDING BEHAVIOUR IN X IRRADIATED RATSB. gMAJDA. I. 5ATELIW&. I. AHLERSDepartment of General Biology, Faculty of Science,5afa>ik University, KoSice, CSSRThe effects of ionising radiation on the regulationof food intake in rat was studied. The distributionof food intake during the day, the meal size andmeal frequency of male Wistar rats housed indivi-dually in a room with arteficial light regimen LD12:12 were recorded continually by an automaticequipment. After a one-week control period 3 expe-rimental groups were created (n*8) : 1/animals ir-radiated with a whole-body exposition of 2.39 Gyx-rays, 2/ irradiated with a dose of 5.73 Gy and3/ shame irradiated animals. Both doses caused anabrupt decrease in total food intake during thefirst 3 days after irradiation, folloved by a gra-dual return to control level. This effect was morepronounced at the higher dose with return to normallevel on the 9th day. The daily rhythm of food in-take was only slighly modified : a transient dis-turbtion of the rhythm was observed only during the3d day after irradiation. It was found, that up to80 % of the food intake decrease fell on the lightperiod, due to a decrease of meal size and mealfrequency, whereas in the dark period the meal sizewas even increased and the meal frequency onlyslightly deoreased. It seems, that the radiationeffects food intake regulation differently duringthe light and dark periods.

234

RADIATION-INDUCED CHANGES OF TOLUIDINE BLUE

UPTAKE AND GLYCEROL LYSIS TIME IN ERYTHROCYTES

M. SOLLE

Natl. Board of Atomic Safety and Radiation Pro-fection, Inst. of Medicine, Berlin, GDR.

Measuring of toluidine blue (TB) uptake (Green-

wait, 1978, Brit.D.Haematol., 39,545) and of the

time required for 50 £ hemolysis-GLT -(Gottfried,

1974,3.Lab.Clin.Hed.,83,323) were used to analyse

blood samples of X-irradiated rats (2, 4 and 6Gy)

for erythrocyte abnormalities.

TB uptake decreases on day 1 to 3 and increases

between..day 10 and 30 after irradiation.

The values of GLT_O show similar but less marked

changes.

The period of increased T3 uptake and GLT Qparallels the time of elevated reticulocyte

numbers.

235

MORPHOLOGICAL DETECTION OF SURFACE CHARGES OFX-IRRADIATED FIBROBLASTS

Z.SOMOSY, Tamara KUBASOVA, G.J. KO" TELES

"Frederic Joliot-Curie" National Research Institutefor Radio-biology and Radiohygiene, H-1775. Budapest/POB.101. Hungary

The extension of sites, density and topology of nega-tive surface charges of primary human embryo fibro-blasts were investigated by electronmicroscopic exam-ination of plasma membranes for the amount and dis-tribution of cationized ferritin /CF/ bound to it/Somosy et al.,1984, Cell Biol.Int.Reps. £,407-413/.CF bindings on the apical and lateral surfaces werescattered in small groups. On the basal regions onlycell-to-cell junctions were labelled. Following x-ir-radiation with 2,5 Gy the area covered by CF and thenumber of ferritin particles per unit area of bindingsites decreased /Koteles et al.,1983,Biological Ef-fects of Low-Level Radiation,IAEA,Vienna,pp.115-128/.By semLquantitative evaluation it was found recentlythat the effect developed rapidly and it proved to bereversible. The degree of negative charge density perum2 reached a minimum of 41 per cent of control in 10minutes, then returned to the control level after anhour. The coverage of apical membrane of unirradiatedcells was 42 per cent, upon irradiation it decreasedto 24 per cent in 10 minutes, then returned and evenexceeded slightly the control in an hour. Radiationtreatment did not influence the polarity of surfacenegative charges, though reduced its extent. Similartendency of alterations was induced by 0,25 Gy, too.

236

DEPTH-DOSE STUDIES IN RELATIVISTIC CHARGED PARTICLEBEAMS WITH PASSIVE DETECTORg.SPURNYInstitute of Radiation Dosimetry,CzechoslovakAcademy of Sciences,Prague,CSSR

Some passive detectors can be also very usefulto specify dosimetric charakteristics in relativis-tic charged particle beams used for radiobiologicalapplications.We studied possibilities to use forsuch purposes:-thermoluminescent detectors(TLD)jlike LiF,and Cze-choslovak alumophosphate glassesjand

-solid state nuclear track detectors(SSNTD),if se-condary charged particles created inside detectorsby primary radiation are registrated;polymers likepolycarbonates,polyesters,and cellulose derivati-ves ware used.

First,we established responses of such passivedetectors to protons,helium,and carbon nuclei ofenergies about 4GeV per amu.lt was proved,that res-ponses are sufficient to cover tissue dose rangesfrom 0,1mGy to several "lO Gy.

Detectors studied were used to study some impor-tant dosimetric characteristics of mentioned parti-cle s beams,like:-dose profiles in particle beams as a function ofaccelerating parameters(focusation,etc.);-depth doses in small-animal phantom represented bya set of polymethylmethacrylate cylinders*

Re silts obtained are analyzed and compared with in-dependent ionization chambers measurements and withtheoretical calculations.Reasonable agreement ofour TLD data was shown.As far as SSNTD s are con-cerned, they would permit also LET spectrometry ofsecondary charged particles.

237

RESPONSE 07 AIR-JIHED ZOHXZAXXOH GHAMBKRS IN HIUT-RON-GAMMA BEAMSF.SPtJRHY.I.VOTOCKOVAInstitute of Radiation Dosimetry,CzechoslovakAcademy of Sciences,Prague,CSSR

Properties of air-filled ionization chambers withwalls made from tissue-equivalent plastic (A15G)oraluminium (both 1,42cnPin volume)resp.,for theirusing in neutron-gamma beam dosimetry were studied.We established theirs relative responses to photonswith energies below 100keV,it was found out thataluminium chambers can overestimate gamma dose up toa factor of about 5.Their relative responses werealso studied for neutrons of energies between 0,57and 15MeV.For chamber with tissue-equivalent wall itwas proved that its response approaches to the sameof fully homogeneous chamber rather rapidly withIncreasing neutron energy.An analytical expressionwas calculated to fit observed energetical dependen-ce in full energy range.For aluminium-walled chamber,obtained experimental data are in all cases muchhigher for air-filled if compare to argon-filledchamber.A comparison with theoretically calculatedkerznas in different materials is also presented.Possible influence of humidity on the response ofair-filled ionization chamber is also analyzed.lt isshown that such influence is not excessive,increaseswhen energy decreases.Some applications of air--filled chambers are proposed.

238 .

ABSORBED DOSE RECEIVED BY CHIIDREN SUBJECTED TO X-RAY EXAMINA-TIONS

M. A.STflNISZEWSKA, J.JANKOWSKE

Institute of Occupational Medicine, &5di, Poland

From literature is known that the risk-connected with theexposure to ionizing radiation is evidently higher for childrenand teen-agers than for adults. The purpose of this study isan analyze of risk to children resulted from performing of ba-sic diagnostic X-ray examinations. Up to now the absorbed dosesto especially radiosensitive organs were computed for child atgiven age as the effect of exposure to X-ray in conditions re -presenting for the following examinations:1 - urography AP-pro jection ,2 - cystography AP-projection ,3 - chest radiography PA-projection ,4 - skull and frontal sinuses fluorography JA and left-late-ral projections .According to data collected by our Institute specified above

examinations amount about 50% of total number of X-ray examina-tions of children which are yearly performed in Poland, The ab-sorbed organ doses have been theoretically computed; MonteCarlo method of stimulation has been used for this purpose.A child was represented by suitable mathematical phantan. Thecomputations were performed for 1,5,10 and 15 years old subjectsand adult man. The average exposure conditions which were com-plied with the particular examination for the child fran givenage group were elaborated on the basis of data collected by ourInstitute earlier. The obtained results of computations arecomparable with the adequate literature data.

239

ABSORBED DOSE RECEIVED BY PATIENTS SUBJECTED TO RADIOISOTO-PIC IN VIVO PROCEDURES

M.A.STANISZEWSKA, J.JANK0W5KI

Institute of Occupational Medicine, i/Sd£, Poland

Diagnostic radioisotope in vivo examinations have beenperformed in Poland for about 20 years. According to the re-sults of analyze carried cut by our Institute the annual fre-quency of these examinations in about 2 per 1000 inhabitants.

Up to now the values of absorbed doses to especially radio-sensitive organs were determined, as well as the values ofthe effective dose equivalents for patients subjected to exa-mination of particular types. The values of absorbed doseswere computed on the basis of literature data concerning tobiodistriiwtion of particular radiopharmaceutics. A specialremark was payed to the thyroid procedures performed afteradministration of ^J-sodiun iodide, because these examina-tions anount over 55% of total number of radioisotope in vivoexaninations carried out in Poland in 1981. If the value ofeffective dose equivalent ( per unit of administered activity)is treated as an indicator of patient risk in analyzed proce-dure - the most riskfull to patient are radioisotope in vivoexaninations performed after administration of following can-pounds labelled 131J:1 - sodium iodide,2 - macroagreggates of albumine,3 - Bengal rose,4 - human serum albumine,5 - hippurate.

240

ENHANCED RADIATION DAMAGE TO ICDODEOXURIDINE--LABELLED CELLS AFTER IRRADIATION WITH Cs-GMWA-OR SOFT X-RAYS.S. SUNDELL-BERGMftN, K.J. JOHANSON AND S. RICHTER

Department of Radioecology, The Swedish Universityof Agricultural Sciences, Box 7031, S-750 07Uppsala, Sweden.

I incorporated into DNA as iododeoxy-uridine(IUdR) has been shown to be extremelyradiotoxic to cells. This high radiotoxicity hasbeen attributed to the highly localized energydeposition by Auger electrons-released in an

I-decay. Replacement of I with stable iodinefollowed by irradiation with external photons ofappropriate energies stimulates the release ofAuger-electrons and an enhanced radiobiologicaleffect is achieved. The induction and repair of DNAstrand breaks in CHO-cells after irradiation with

Cs-gamma- or soft X-rays have been investigated.The number of DNA strand breaks was determined usingthe DNA unrninding technique with double-labelling.In cells labelled with IUdR more DNA strand breakswere induced and these breaks were also lessefficient repaired. The damaging effects were morepronounced after irradiation with soft X-rays. Inaddition cell survival of CHOcells after labellingwith lUdR and irradiation with Cs-gamma- or softX-rays were studied. The survival of iUdR-labelledcells was much less than of control cells after bothirradiations.

241

EFFECT OF CYCLOPHOSPHAMIDE ON HEMOPOIETIC ORGANSIN RAT. CHANGES IN DNA AND BASIC PROTEINS.J.SeLIOVA\ N.MACXOVA*, M.HVIZDOSOVA, E.MlgtfROVA

Department of General Biology, Faculty of Science,P. J. §af»rik Unirereity, Ko5i.ce, CSSR

Effect of cyclophoBphamide /CP/ on the weightand cellularity, DNA and basic protein content innuclei of bone narrow, thyBUB and spleen of ratswas studied. Animals were examined 6, 12 and 24hours and 3, 5, 10, 20 and 30 days after intraperi-toneal application of CP in the doses 100 and 200mg/kg of body weight. From the 5th day after appli-cation marked decrease in weight and cellularityof all organs was obserred. Amounts of DNA and ba-sic proteins in nuclei ot bone marrow and spleenwere higher as compared to controls and their in-crease occured prior to reparation of cellularityand organ weight, that was initiated within 5 and10 days after CF application. Changes in thymuspersisted for longer period of time and reparationwas incomplete eren at the day 30 after CP appli-cation. In accordance with these data no increasein DNA and basic protein amounts in thymus nucleiwas obserred.

242

A RADIOMODIFYING EFFECT OF HYPOXIA AND HYPOXICPROTECTORS FOLLOWING FAST NEUTRON IRRADIATIONA. Sverdlov, G.KalmikovasN,Nikanorova, S.TimoshenkoLeningrad Nuclear Physics Institute.Gatchina. USSR

The efficiency of anoxia and of combination of5-MOT with sulphur containing protectors was stu-died in the experiments on neutron-irradiated new-born and adult mice. The mean energy of fast neut-rons was 0*85 MeV.Anoxia increased the survival ofnewborn mice with DRF a 1,66 and the one of spleenhaemopoietic stem cells with DRF = 1.8, DRF underJ-irradiation 200 KeV was 2,49 and 2,94 respective-ly. Four chemical combinations of 5-MOI were used:1)with WR-2721 and Cystamine 2)with AET and Cysta-mine 3)with WR-2721 and AET 4)with Cystamine andCystaphos* All of four combinations increased thesurvival of adult mice irradiated with 2,0 -2,75Gyat 40-90% as compared to control ones. Anoxia andcombinations of protectors decreased the damage ofthe intestinal mucosa membrane and accelerated therecovery processes in the intestinal. Our experi-ments convince of the effectiveness of hypoxia andhypoxic protectors under neutron irradiation.

243EARLY REPARATION OF HEMOPOIESIS AFTER LOCAL 20 GIOAJUIA IRRADIATION IN RATSV. SVOBODAFurkynt Medical Research Institute, Hradec Kralove*,CSSR

The change* of CFUs number* in unirradiated andirradiated bone narrow (EM) areas and in peripheralblood were studied after single gamaa irradiationof 50% active BM in caudal part of body in whiterats. The cellularity and incorporation of 59 Feinte BM were also investigated.

In irradiated area was achieved the praeirradia-tion level of BH cellularity am early as the 8thday after the exposure. The incorporation of 59 Fewas normal at the day 5 following irradiation. Inlead layer shilding area were found the highestincreased incoithe tine of max]area.

The first early significant increase of CFUscounts ia peripheral blood of rat we succeeded toprove at 30 Minutes after the radiatioa and theelevation of CFUs continues within 12 hours. Thesechange are in time coincidence with gradual growthof CFUa in BM of shilding area with maximum 2 hoursand in damaged area 12 hours after irradiation.

These facts indicate that the early answer ofheaopoietic system after local daaage is reactionof one functional coapartaent. This answer reflectof count changes and state of function activityCFUs. Stea cells are produced and released froaundamaged part of BM and after aigration in peri-pheral blood are seeding in to damaged BM parts.

i. w •*•»«*) mu* wma v»w* w A V W M M M*AW » ( A Q M « B V

»rporation 59 Fe on the 3th day. atixiaal local BM daaage in irradiated

244

CFU-S SURVIVING UNDER THE LONG-TERM CONTAMINATION

V/ITH PLUTONIUM-239

VL.SVOBODA. A.SEDLXK, Z.KOTA^KOVX

Institute of Hygiene and EpidemiologytPrague,CSSR

Radiosensitivity, self-renewal and prolifera-

tive capacity were studied in murine pluripotent

hemopoietic stem cells <CFU-S) after i.v. injection

of 239Pu (194,199 and 14 kBqAg). The measurements

were carried out using CFU-S assay combined with ad-

ditional X-irradiation, double transplantation as-

say, labeling of proliferating cells with yIUdR,

'^Fe-uptake technique, quantitative cytology. The

CFU-S were more radiosensitive than controls and

their self-renewal capacity was impaired. Production

of differentiating progeny and ^Fe-uptake per

a single spleen colony were reduced. After injecti-

on of 14 kBq 3'Pu/kg investigated parameters were

significantly affected as well. Impaired functions

and increased radiosensitivity of the stem cells

can alter life expectancy of the contaminated orga-

nism especially under the risk of repeated exposure

to the toxic agents.

245

STUDY OP BIOLOGICAL EFFECTS OF MICROWAVE IRRADIA-TION ON RATS

L.D.SZAB6. G.THUR^CZY, G.KUBINYI, M.BOD*, andTTTREDHSRS ZKT'FJC'Natl.Res.Inst.for Radiobiology and Radio-hygiene, Budapest, Hungary

It is knovm that the effects of microwave irra-diations on biological systems can be divided intothermal and non-thermal effects. In our experimentswe used different dose rates (between 1 mWcm2 and5 mW/cm2) at 2450 + 50 MHz frequency.The irradia-tions were performed in free space. Our experiment-al objects were 180 g male F^ hybrid rats. We stup-ed the changes of several biopotentials (EEG,EKG,REG,impedance,etc.) before,during and after micro-wave irradiation and at the same time we observedchanges in the temperature with thermocouple(+ 0.02°C sensitivity).All of this signes were re-gistered on the tape. Data obtained were preproceiB-ed on the frequency analyzer and the analogue todigital conversion was made on a microcomputer.During 50 min irradiation at JmW/cm^ power densitywe could observe changes in the EKG,REG and impe-dance. The changes of the EEG were non-significant.All of the changes observed were transient because50 min after the irradiation changes disappeared.During and after irradiation the change of thetemperature was not measurable.Conclusions: The whole-body irradiation of rats at3mW/cm2 power density (2450+50 MHz,continuous wave)is a threshold level at which some of the biopoten-tials transiently changed. Phenomena observed wesuggest to be non-thermal effect.

246

INVERSE CR0S3-SENSITIVITY TO UV-C AND X OR GAMMARADIATIONS OP TWO STRAINS OP L5178Y MOUSELYMPHOMA: A TENTATIVE EXPLANATION

I. S2UMIEL. D. WLODEK, K.J. JOHANSON* E. BUDZICKA,E. NIEPOKOJCZYCKAInstitute of Nuclear Chemistry Technology,Warsaw, Poland and**The Swedish University ofAgricultural Sciences, Uppsala, Sweden

Two strains of L5178Y (LY) cells are inverselycross-sensitive to X and UV-C radiations (l£= 0.9and 0.5 Gy, Dov = 2.8 and 9.0 Jm"afor LY-R and LY-Scells, respectively). We examined the effect ofbenzamide on the cellular response to X (or gamma)and UV-C irradiation. Increased lethal effect andan apparent inhibition of repair were observedonly in the case of LY-S cells. A decrease in NADcontent was found, more pronounced in gamma-irra-diated LY-S than in LY-R cellsj after UV-C irradia-tion the decrease was.only seen in LY—S cells.Using alkaline DNA unwinding technique and araCwe found that UV-C irradiated LY-R cells do notincise DNA strands, in contrast with LY-D cells.We interprete these results as indicating thatactivities of UV-endonuclease and ligase are thekey factors defining sensitivities of LY-R andLY-S cells to X (or gamma) and UV-C radiations.The activity differences presumably depend onspecific features of chromatin architecture ofLY-R and LY-S cells.

247

C1IANG13S IN THE INTRINSIC FLUOJIESCIJNCiCOF LYWH0CYT3S AFTSll XMWJXATTor.

IS «TATARA,f K .TVAIlogKOVAttasearch Institute of Preventive Medicine,Dratislava,CSSR

Intrinsic fluorescence of rat's periphgrallyuphocytes 3€$ e r *-n vivo irz*adiation with Co;ar.ana and/or Cf neutron field has been studied.The emission spectra and the polarisation offcryptophan fluorescence of lymphocyte suspensionvore measured 48 hours aftor irradiation. Theexperimental animals wore exposed to farnriairradiation within the dose raAge of O.2f5 to k Gyat the dose rate of 0.5 Gy/min. Exposure to,-anmia-neutron field was in the dose ranê of 0.1uo 0.5 Gy at the dose rate of 0.5 mGy/min.Fluorescence intensity increased with increasingdose and was fitted by linear relationsliip withthe correlation cooficient of 0.954. Resultsobtainod in the case of neutron irradiationrovealod a steeper increase of fluorescence withRBii 3«3» Polarisation of fluorescence decreasedwith increasing doso at a similar RBI2 value. Itwas concluded that tho conformational chances oflymphocyte membrane proteins aro brought about bylow docos of both cemana. mid neutron irradiation aswo 11..

248

GROWTH AND DIFFERENTIATION DYNAMICS IN MOUSEEXOGENOUS SPLEEN COLONIESL. TKADLESEK, M. HOFER, 5, VIKLICKA, Z, KARPFELInstitute of Biophysics, Czechoalovak Acadaay ofSciences, Brno, CSSR.

Male (CBA x C52BL/10) F, nice ware whole-bodyirradiated with Co gamma raya (doae of 9 Gy).Five hours later they were given 1, v. a suspensionof isogenic bone narrow cells. The nuaber of injec-ted nucleated elements decreased according to theinterval between irradiation and the sacrifice ofmice: from 6 . 10° (three days) to S . 10* (sixdays). At the fixed day (3rd, 4th, 5th and 6th) thenice were killed and their aplaens divided into twoparts. One of then wae fixed in Helly solution andprocessed for serial paraffin aections and lightMicroscopic investigation. The other part was di-vided into 1 an slabs that were fixed for electronMicroscopy and enbedded into Spurr aediua. Sealthinsections, cut fro* then, were also used for lightMicroscopy. Colonies coaposed of Morphologicallyundifferentiated cells were found froa the third tothe fifth days after irradiation. Differentiationproceeded faster in granulocyte producing colonies!groups of aetaayelocytes ware found by the thirdday. On the other hand, still on the sixth dayerythropoietic colonies were composed Mainly ofyounger erythroblaatic cell series. Exceptionalbigger and More differentiated erythropoieticcolonies Might be of endogenous origin.

249

ENZYME TEST FOR EARLY PROGNOSTICATION HEAVINESS OFRADIATION DISEASE AT LAMBS

CODOROVB. TCKigheLgher Institute of Veterinary Medicine, StaraZagora, Bulgaria

It is supposed in view of an early prognostica-tion of Acute Radiation Disease (ARD) heaviness inthe first 15-24h after the irradiation in the bloodplasm of lambs the changes in cytoplasmic enzymesSorbitoldehydrogenase (SDH), Lactatdehydrogenase(LDH), Cholinesterase (ChE), GPT activity and i»o-enzyme of LDH to be studied. In the period 1-3day the activity of organelospecific enzymes GOT,Glutamatedehydrogenase (GDH) and Acide Phosphatase(AP) must be investigated.

When the activity of LDH, SDH, ChE and GPT isnot increased in the first 15-24h, it concerns toa simple form of ARD. When in that period the ac-tivity of these enzymes is increased 4-5 or moretime it concerns to heavy and superheavy form. Atheavy and superheavy form in that period the acti-vity of liver specific isoenzymic fraction LDH~ isincreased strongly. At the simple form the activityof GDH, AP and GOT does not change in blood plasm,while at heavy and superheavy forma their activityis increased strongly 24h after irradiation.

250

EFFECT 0 ? LOW DOSKS cFtf-KAYS OK GROWTH OP;.:AIZE AND SOYA-BEAKL.S XUAK TU. DAKG VAK HAKHInstitute of Biology, Hanoi, SRV.Effects of low doses of if-irradiation on maizeend soye-bean had been studied in conditions ofVietnam. We utilized some different varieties su-ch as maize VM1, IH2A, soya-bean DT70, DT74 to bestudying objects * The dry seeds of them were% -irradiated with doses 0-1200r for maize andO-25OOr for soya-bean. The results of comparativeexperiments showed that growth of maize wasstimulated by doses 6OO-8OOr. The yield of irra-diated plants of varieties VM1, TH2A enhanced 26^14& in comparison with control respectively. Thestimulatory doses of soya-bean are 800-1200r. Theyield of soya-bean DT70, DT74 increased 13#, 17£respectively. The mentioned results are meanvalue of harvests for many years and their repro-ducibility is certain.Besides of the yield, the quality of production

is proved as well. The total protein contents ofseeds which were given by irradiated plants ofmaize VIM, TH2A, soya-bean DT70, DT74 increased16%, 17&, 11i», 14fr respectively.We proposed a mechanism of radiostimulation

which connects with biosynthesis of growth subs-tance Indol-Acetic acid (XAA). The activities ofEnzymes such as Trlptophantransaminnase andTrlptophandehydrogennase which take part in IAAbiosynthesis reaction and IAA content increased235-, 11£, 17# in comparison with control respec-tively.

251EVALUATION OF EFFECTIVENESS OF STABLE IODINE PROPHY-LAXIS COMPARING DATA OF ANIMAL EXPERIMENTS AND OFCOMPUTER SIMULATIONS

"FJC" iatl. Res. Inst. for Rad. biol. and Rad. Hyg.Budapest, Hungary

As is known stable iodine compounds given immedi-ately (but at least within 2 hrs) before or afterthe accidental intake of radioiodine can considera-bly reduce the radiation burden to the thyroid gland.Our similar results have also been reported (Turai,1982, Izotoptechnika, 2£,218). In our experimentsoptimal blocking of thyroid of CFY rats with 25Ogav.b.w. could be reached with 0.5-1.0 mg KI admini-stered within 0.5 hr following the 131-1 intake. Ex-trapolating this amount of KI (potassium iodide) forthe reference man, it equals to 140-280 mg of KI*These values fit data obtained in volunteers (Ilyined.,Atomizdat, Moscow, 1972 and NCRP, Report 55»Wash.D.C.,1977).

Results of computer simulations, obtained in ourversion of Johnson s modified iodine kinetics model(Johnson, 1981, J. Radioanal. Chem. 1-2. 223), pro-ve our experimental findings according to the effec-tiveness of iodine prophylaxis depending on the ave-rage daily iodine intake and on sdheme of the stab-le iodine administration. Thus, the lower the dailyiodine intake, the smaller the protective effect oflarge doses of KI given* The effectiveness of iodi-ne prophylaxis decreases considerably with increaseof the interval between radioactive and stable iodi-ne intake, however, the further reduction of thyroidgland dose by means of elevation of iodine dosesapplied at the same intervals is rather small bothin animal experiments and computer modeling studies.

252MODIFICATION OF RADIATION EFFECT BY THE SPLEENEXTRACT OF THE TURTLE (TESTUDO HORSFIELDI)A.A. TURDIYEV. R.B. USMANOVInstitute of Zoology and Paraaitology, TashkentUSSR

In recant years the possibility to use varioushumoral factors for recovering from poetradiatiomchanges has bean given considerable attention byradiobiologists•

Plasma and extract of Central Asian turtle spleenhave been used to treat the radiation injury of he-matopoietic system of mammals. The efficiency ofblood plasma and spleen extract has been shown tobe rather high. The extract appeared to be effici-ent in low doses. Cell composition of bone marrowof mice treated by lethal doses of radiation hasbeen restored within 8 days following the extractinjection. The survival made up 71.2% to 4*2% incontrols*

Using g#l filtration the turtle spleen activefraction containing PSH (Protein Stimulant of Hemo-poiesis) haa been obtained* Its molecular mass was60-60 th. dalton. PS1 of this fraction has beenfurther purified by cation exchange chromatographyand two fractions have been obtained. PSH waa shownto be present in the second fraction, that warcharacterized by colony-forming activity.

253

HISTOLOGICAI EXAMINATION OF COMBINED EFFECTS OFDIBROMDULLCITE TREATMENT AND DIFFERENTLY FRACTION-ATED X-IRRADIATIONS IN TRANSPLANTED SOLID EHR-LICH CARCINOMA OF MICE

E.UNGER'

F.J.C. National Research Inst. for Radiobiologyand Radiohygiene, Budapest, Hungary

Histological damages were compared on paraffin--embedded, haematoxylin-eosin stained sectionsof transplanted solid Ehrlich carcinomas of CFLPmice in different intervals after completingtreatment with 4 x 250 mg per kg body weightdibromdulcite /USD/ alone or two different cours-es of fractionated X-irradiation /50 Gy totaldose in both cases/ combined with DBD treatmentas above, respectively. Compared with adriamycintreatment studied formerly, the damaging effectof DBD observed by histological techniques provedto be more expressed* Damage was much more obviousafter combined treatment than after the sole oneby DBD« The difference between the effects of thetwo differing courses of fractionated X-irradiationwas not unequivocal: higher X-ray fractions givenmore rarely seemed to produce greater effect on theground of some parameters than lower doses applic-ated more often while the latter seemed to be moreeffective on the ground of other criteria*

254

THE INFLUENCE OF THE IRRADIATION fiEGIME UPON THE INACTIVATIONOF MYGOTOXINS UNDER EXPEWUffiNTAL CONDITIONSM.URALOVA. N.PATZBLTOVX. F.HAVLJK

iiesearch Institute of Preventive MedicineBratialava, SSSB

The paper handles the problem of the inactivation of thetoxigenic strain Aspergillus flavus following the applicationof gamma radiation to wheat* The aaount of the applied doseand of the absorbed dose of ionising radiation upon the inhi-bition of mycelium growth and toxin production. Ike aflatoxinBi was determined by extracting in chloroform and developedon Silufol a within the chloroform a acetone system. The app-lied doaes of gamma radiation /3-3O kGy/ have shown that theabsorbed dose doea not inhibit aflatoxin production* By com-bining the action of ganaa radiation with the modification cfsome physical factors, however, an optimal inactivation wasreached. With the help of toxlcologico-genetical tests /theDominant-Lethal Nutations Test, the Three-Generations Test/the influence was traced of irradiated substrates upon thehealth of experimental animals* It follows from the resultsobtained that in long-term feeding with contaminated wheat ir-ratiated by gamma rays no positive mutagenic activity has beenrecorded which allows to presume that wheat of humidity ot25 % contaminated by a weakly toxigenic strain A.flavus irra-diated by a dose of 6 kCy, and wheat of a humidity of 13-15 %,contaminated by a strongly toxinogenie strain of A.flavus, ir-radiated by a dose of 6 kGy, are no genetic risk for whiterats.

255

DIFFERENCES IN RADIOPROTECTIVE EFFECTS OF HYPOXICHYPOXIA IN NORMAL TISSUES AND IN EXPERIMENTALTUMOURSA. Vacek. D. Rotkovek*. A. Bartonickov*, T. Taftev"Institute of Biophysics, Czech. Acad. Sci., Brnoand "Institute of Clinical and ExperiaentalOncology, Brno, Czechoslovakia

In experiment* on rats of Wistar strain ire stud-ied the radioprotective effectiveness of hypoxichypoxia (10 % O2) against radiation daaage of theintestine and heaatopoietic tissue and also that inthe radiation treatment of experiaental subcutaneoustumours induced by Walker carclnoaa cells. Irradia-tion of rats in 10 % 0 2 reduced the daaage of theintestine, as wall as that of heaatopoietic stsacells of the bone marrow. With the uaa of highdoses of ganna rays on located areas of the skinthe effect of "burn" was less narked in hypoxiaprotected rats as coaparsd with thoss irradiated inair. The regression of the experimental subcutaneoustumour treated locally with a eingle doss of 57.5 Gyof gaaaa rays showed no diffsrsncss if irradiationwas performed in 10 % O2 or in air. The reductionof the protective effect of 10 % O2 in the experi-aental tumour is related to the low values of pO2in the tumour which were not changed during hypoxia.The results indicate that 10 % O2 hypoxia can beused for protection of normal tissues during radio-therapy.

256

USE OF LABELLED IRON FOR DETERMINATION OF POSTIR-RAOIATIONAL INTENSITY OF ERYTHROPOIESIS ON THE BASEOF FERROKINETIC MEASUREMENTS3. VACHA. V. ZNOOIL, 3. HOLAInstitute of Biophysics, Czech»Acad.Sci.,Brno, CSSR

Incorporation of labelled iron (59Fe) into matu-ring erythrocytes (RBC) is the only method capableof measuring the intensity of erythropoiesis (EP)in vivo so far. The authors worked out a series ofpartial techniques to overcome interfering ferro-and cytokinetic factors burdening the method. Theyare: preparing 59Fe-labelled transferrin for smallplasma samples (Hola et al.,1979,Acta Haemat.,61,55); abolishing the influence of hemolysis on plas-ma Fe determination (Hol£ et al.,1975,Clin.Chim.Acta,6JL., 121); extracting the hema iron from thebone marrow (Vacha et al.,1978,Exp.Hematol. ,6_,718);correcting the radiactivity of RBC.and plasma cir-culating in EP organs (Vdcha et al.,1980,ActaHaemat.,6£, 165); distribution of erythropoiesis(V£cha et al,, 1982, Exp.Hematol. ,1C), 768) and of hemeand non-heme Fe fractions in EP system (Vacha et al.,1983,Exp.Hematol.,11,,714); a mathematical model ofinternal iron kinetics in an organism (Vacha et al.,1982,Acta Vet.Brno,51,3) and in individual EP re-gions (V3cha et al.7T984,Acta Vet.Brno,53,119).A procedure enabling us to measure EP intensity withthe exclusion of the majority of interfering factorswas worked out on the basis of the papers referredto. EPtr(A-E)C.D, where A is the radioactivity ofheme 59Fe in EP organs 6 h after the tracer admini-stration, E refers to the same in RBC.circulatingIn El= organs, C is the plasma Fe concentration,D «0/^f(t).g{6-t)dt, where f(t) is 59Fe plasmaclearance and g(6-t) represents the course of 59Feradioactivity leaving the organ.

257

SPECIES SPECIFIC FEATURES OF RECIPROCAL TRANSLOCA-TIONS INDUCED BY SPERMATOGONIAL IRRADIATION INMAMMALSA. VAGLEKOV. I. BAEVInstitute of Roentgenology and Radiobiology,Sofia,Bulgaria

The work described was based on data in the lite-rature and findings at this laboratory in mouse,ratSyrian hamster,and rabbit.Considered were the ra-tios of principal quadrivalents(rings:chains) observed in spermatocytes at diakinesis-metaphase of thefirst meiotic division.From this standpoint,the mammals studied thus far may be distributed into: agroup where the ratio is in favor of chain multiva-lents(guinea pig); a group where rings rather thanchains are more commonly prevalent(mouse,Syrian hamster); and a group,as yet the most numerous,whererings sharply predominate (rabbit,rat,Macaca rhesusand probably man).

Our results constituted a binding unit that per-mitted us to form a novel conception (rather a hy-pothesis) providing a reasonable explanation forthe occurrence (under varying irradiation condi-tions) of species differences in principal quadri-valent ratios.We believe these to be determined bya complex of factors,major importance being attri-buted in our hypothesis to the following: (a)numberand extent of chiasma terminalization; (b)species-specific radiosensitivity to breakage at certainpoints - in the vicinity of centromeres or in termi-nal areas; and (c) species-specific radiosensitivi-ty,competence,capacity,and effectiveness of sperma-togonial systems.

258

RBE OF 9 GeV/NUCLEON PROTON RADIATION

A. VAGLENOV. A. BAJRAKOVA (Bulgaria), E» FEDORENKOA. KABACHENKO (USSR)

Institute of Roentgenology and Radiobiology,Sofia(Bulgaria); and Health Ministry Institute of Bio-medical Problems,Moscow (USSR)

Dose-response relations for reciprocal translocations induced in mouse spermatogonia by exposureto protons with energy 9 GeV/nucleon were studied,comparisons being made with findings from mice gi-ven oOCo gamma irradiation at 1.44 Gy/min.

Increases in translocation yields with rise inproton dose were found to be less than those pro-duced by gamma irradiation.The translocation ratesobserved for gamma-ray and proton exposures,res-pectively, were as follows: with 0.5 Gy, 0.2 andO.5%« 1 Gy, ; and 1.3%* 2 Gy, 4.3 and 3.0%; and 4Gy, 6.5 and 4.5%.Within the dose range 0-4 Gy,a good fit to expe-

rimental data for gamma rays and protons,respecti-vely, were the linear models: Y =-0.255+(1?.7+2.3)10-5 D, and Y =-O.O375+(13.9±O.6)1O-5D, where Y istranslocation yield in % and D is radiation do¥ein cGy.Prom comparison of slopes of the regressionlines,an RBE coefficient of approximately 0.8 wasobtained for protons relative to gamma radiation.

259

GAMMA DOSE RATE EFFECT ON GENETIC DAMAGE IN MAM-MALS. ESTIMATION OF HUMAN RISK

A. VAGLENOV. A. KARADZHOVInstitute of Roentgenology and Radiobiology,Sofia,Bulgaria

Gamma dose response for translocation yields in-duced in spermatogonia was studied in mouse,rat,Syrian hamster,and rabbit exposed at the followingdose rates: 1.23, 0.25, 8x10~2, 7x10" and ixKT*Gy/min.The threshold dose rate below which genetic da-

mage remained unaffected was found to be species-specific. It may be expected that the level of mi-nimal, unrepairable genetic damage may likewiseprove to be species-specific.In this context,ourfindings did not rule out the possibility thatwith still lower dose rates genetic lesions in rathamster,and especially rabbit could be maintained,reduced,or even enhanced.It is suggested that,because of similarities in

genetic radiosensitivity between rat and man,thelevel of 3.4x10-4 translocations per cell per cGymay serve as a baseline for acute photon-exposureconditions.For chronic gamma-ray exposures,it is recommen-

ded to use a correlation coefficient equal to 0.5*This is based on the peak magnitude of geneticdamage found by us in the mammals investigated.

260

UNIVALENTS AND FRAGMENTS IN MAMMALIAN MEIOSISA. VAGLENOV. V. MANCHEVInstitute of Roentgenology and Radiobiology,Sofia,BulgariaOccurrence of univalents and fragments in diaki-

nesis-metaphase 1 spermatocytes was studied aftergamma-ray exposure givem at varying dose rates tomouse,rat,Syrian hamster,and rabbit.Frequencies of univalents,resulting from XI and

autosomal bivalent disjoining,and of fragmentsshowed no dependence upon dose and dose rate.Thus,rabbit and mouse were equal in fragment frequency,which was three times that for hamster and rat.Go-no somal univalents were more prevalent in mouse,Syrian hamster,and rabbit,the converse being truefor rat.Autosomal univalent frequency was the same,and about two and a half times higher,in mouse andrabbit.A similar situation ensued for gonosomal univalents,with rat significantly superior in frequency as compared to hamster.Therefore,species specificity was revealed in

occurrence of gonosomal and,to some extent,of au-tosomal univalents.lt is quite probable that thedifferences encountered in frequencies of autoso-mal univalents and,especially,of fragments are largely to be accounted for by variations in the te-chniques used.In a comparative aspect,the order ofthe mammalian species investigated thus far is asfollows:the primate representstive,Macaca rhesus,has the lowest frequency of univalents and frag-ments frequencies rise in rat followed by Syrianhamster,and are very high in mouse and rabbit.

261

MUTABILITY AND RADIOSENSITIVITY OF CULTUREDCHINESE HAMSTER OVARY CELLS EXPOSED TO LOW DOSERATE OF TRITIUM BETA RADIATION

L.P. VARGA, Sarolta GUNDY, J. NAMENYI andI. SZEGEDI

"Frederic Joliot-Curie" National ResearchInstitute for Radiobiology and Radiohygiene,Budapest, Hungary

The long term effect of tritium beta radiationwas studied on Chinese hamster ovary cells main-tained continuously for months in medium contai-ning tritium oxide (HTO) or tritiated thymidine(5HTdR) at concentration of 3»7 kBq-37 Bq/ml.During the incubation period the induced genemutations were determined for the hypoxanthine-guanine-phosphoribosyl transferase (HGPRT) locus,the chromosomal aberrations and sister chromatidexchanges were analysed by standard methods.Radiosensitivity of cells was expressed as afunction of inactivation rate after exposure toX-rays.According to the experimental data the chronic

tritium beta irradiation resulted in a biphasicresponse in mutations tested. After 1-2 months*exposure to tritium there appeared a more effec-tive reparation, while in. later time (3-6 months'exposure) there developed a hypermutability ofcells which was verified by treatment of cellswith a chemical mutagen, ethyl methane sulfonate(EMS). As regard the radiosensitivity, nodifference could be observed as compared withthe controls.

2 6 2

CHANGES INDUCED IN THE HEMATOPOIETIC AND LYMPHOIDSYSTEM OF IRRADIATED MICE BY THE DOUBLE-STRANDED

HradecVAVROVA* J.. PETYREK P.Purkyne Medical Research Institute,fiSSR

Syatenic (i.p.) single injection of ds RMA. anindueer of interferon, 17 hours before gamma irra-diation of mice, increases significantly the weightof the spleen, cellularity of the bone narrow, num-ber of leucocytes in the peripheral blood and num-ber of endogenous spleen colony forming cells. Thepeak of the increase is evident in 8 days after ir-radiation* Injection of ds RNA 10 minuts before orafter irradiation hae no effect. IgM and IgG anti-body production decrease markedly after irradiationand injection of ds RNA before irradiation.

263

PREFERENTIAL INITIATION OF UNSCHEDULED ONA SYNTHE-SIS ON THE DNA FRAGMENTS A8S0CIATED WITH NUCLEARMATRIXy. vELČoysKf. v.c. BEZLEPKIN*; VU.VU. MALINOVSKY*.A.I. GAZIEVÎnat. Biophya«( Czech. Aead. Sci., Brno, CSSR;4Inet. Biol. Phye., Acad. Sol. USSR, Puehchino.USSR

Distribution of unachadulad DNA aynthaaia (UDS)raaiatant to hydroxyuraa inducad by UV or / -irradia-tion waa obaarvad with raapact to tha coapartaenteof DNA in nuclaar aatrlx (NM) aa wall aa in totalnuclear DNA in tha Zajdela hepetoaa call». Duringtha firat ahortaat incubation intarvala 1.5 ain andS ain after irradiation tha ratea of UDS in thafraction of DNA tightly aaaociatad with nuclaar Ma-trix (aatrlx DNA) mru, raapectlvely, 44 tiaea and17 tlaaa thoaa in tha total nuclaar DNA for UV irra-diation. Aftar | raya thaaa rataa ara 6- and 3-fold,reapectively. During tha prolonged tiae of poetir-*radiation incubation (up to 30 Bin) tha rata of UOSraachaa tha tmám lával in both tha Matrix and thetotal nuelaar DNA. Aftar inhibition of poly(AOP--riboeylation) with nicotinaaida UDS la atiaulatedpradoainantly in tha Matrix DNA. Aaaociation of DNApolyaaraaa 0 and poly(ADP-riboayl)aynthataaa withNM of hapatocytea of noraal and regenerating adultrat liver la deaonetrated. We euggeet that theaaenzyMee mru tha coaponenta of tha aultienzyaaticayetea raaponaibla for IDS in nuclear Matrix com-plex. It can ba concluded that, aiailarly aa in theeaae of replication, the raparativa proceeaea areinitiated on tha nuclaar aatrix, too.

264

THE EFFECT OF HYPERTHERMIA AHD HYPOXIA ONINTRACELLULAR pH

1 2A.M.Vexler , L.L.LitinskayaInstitute of Biological Physics of the USSRAcad.Sci., Fushchino, Moscow Region, USSR;Moscow State University, Faculty of Biology, Moscow

It is generally accepted that radiosensitivity anddeath of cells upon hyperthennia are due to the da-mage to cell membranes. It can be assumed that thefunctioning of the proton pump and/or Na+/H+ exchan-ger in this case is also disturbed, which results inacidification of the cytoplasm. Starting from this,assumption, the effect of hyperthermia on pH of celiscultivated at varying pH of the medium and differentconditions of oxygenation was studied. Chinese ham-ster fibroblasts and pig embryo kidney cells wereused. The intracellular pH (p%) was determined bythe microfluorimetric method using fluoresceinedia-cetate. The required temperature T37°C and 41°C)' wasmaintained by a warm stage in combination with athermochamber. Different conditions of oxygenationwere achieved by placing the cells into an open(normoxia) or closed (hypoxia) chamber. Both thehyperthermia and hypoxia are shown to result in aci-dification of cells. The effect increases with du-ration of exposure to the agents used. The decreaseof pHi is more pronounced when hyperthermia is com-bined with hypoxia or low pH of the medium. The re-sults obtained correlate with the well-known factsthat the magnitude of the damaging and radiosensiti*zing effects of hyperthermia depends on the envi-ronmental conditions.

265

MORPHOLOGY OF RAT HEMOPOIETIC TISSUE ONE YEARAFTER WHOLE-BODY IRRADIATION WITH HIGH-ENERGY(4 GeV/NUCLEON, 4 Gy) HELIUM IQNS

§. VIKLICKA. L. TKADLECEK. M. HOFER. 2. KARPFEL

Institute of Biophysics, Czechoslovak Acadeay ofSciences, Brno, CSSR.

B. S. FEDORENKO. R. A. KABICYNA. A. N. KABACHENKO

Institute of Medical and Biological Problems.Ministry of Health, Oubna, USSR.

Rats were irradiated with helium ions (4 GeV/nucleon, whole-body dose of 4 Gy). After one year,the bone Marrow, inguinal lynph nodes and thespleen were fixed, embedded and sectioned for lightand electron Microscopic investigation. Repair ofacute changes was complete when the space, occupiedby the active and inactive bone mmjrrom (fat cells),was compared in irradiated and control aniaals. The•orphology of the red pulp in spleen sections ofcontrol and irradiated rats was siMilar, too.Striking differences were found between the Morpho-logical picture in lyaph node sections: one yearafter irradiation, the lyaph nodules were saallerand fewer in nuaber. The sinuses were dilated andcontained fewer lyaphocytes. On the contrary, thequantity of reticular and collagen fibres was in-creased in lyMph nodes of irradiated rats. Thesesigns of incoMplete repair of the lyaphatic systeMMight be in relation to the frequent occurrence ofthe asMMary gland cancer that we observed at theend of the first year after irradiation of rats inthis sxperiMent.

266

TIME AND DOSE DEPENDANT CHANGES OF THE FUNCTION OFRAT PITUITARY-GONADAL AXIS AFTER SINGLE-SHOT IRRA-DIATION WITH LOW AND HIGH DOSES GAMMA RATSN. VISHEVA, St. MILANOV, B. IVANOV, I. KURTEVInst. of Roentgenology and Radiobiology, MedicalAcademy, Sofia, Bulgaria

By radioiomunoassay methods were studied thepoatradiation change in hormonal level* of Luteini-zing homon (LH), Follicle-stimulating hormon (FSH)and Testosterone in 330 sexually mature, Bale, Wie-tar rats* The animals were divided into 9 groupsand irradiated with different doses (0.9; 1.0; 2.0;4.0 Gy) gamma rays. The homon levels were assay tedat I-st, 2-nd, 3-rd. 6-th, 20-th, 30-th and 40-thdays after irradiation.

Irradiation of the animals produced dose-dependantand tens-dependant postradiatlon changes in the se-ruK testosterone levels* The values of LH and FSHdisclose a steady decrease to the 40-th day, alsodose-dependant•The present study showed, that the postradiation

damage in rat testis altered totaly the pituitary--gonadal function and also suppressed the develop-ment of gonadal cells.

267

PQ - TISSUE DISTRIBUTION AND ITS RELATION TO THE

AC?ION OF THE HYPOXIC CELL RADIOSENSITIZER /METRO-

NIDAZOLE/

I. VOOICKA, V. CHMELAft, M. ZIttA, K. VOLENEC

Institutt of experimental and clinical radiorbiolo-

gy, Faculty of Medicine, Hradec Kralove, CSSR

Correlations between pO~- distribution and ER

of metronidazole have been studied In the Liver/

small Intestine, spleen and tunours /solid fora

of roshida sarcoma/ of various size In rats. For

pO2- Measurements a needle Pt-microelectrode was

used/ determination of ER for metronidazole was

made by the evaluation of dose-effect curves using

postirradiation volume changes In tumours, weight

changes In the spleen and Incorporation of H-TdR

In the liver and small Intestine as Indicators of

the radiation effect. Co-source /Chisobox/ for

total body Irradiations and therapeutic rtg-sour-

ce /THX 250/ for local Irradiations of tumours

were used. A clear dependence of the ER values on

the po2- distribution /characterized by histo-

grams/, was found In the range of 1,88 for tumours

18 days after cell Inoculation and 0,94 for the

small Intestine.

268

THORACIC SPINAL CORD TOLERANCE IRRADIATION SCHEDULESP.VODVARKA, S.KOZUBEKRegional Hospital Ostrava, Department of Radiothera-py, Peskov, CSSR.

Twenty nine cases of well documented progressivethoracic spinal cord radiation myelopathy were ana-lysed in terms of new DPT - conception (1). The DPTconception has been previously tested against manyanimal experimental data with good agreement. Thecomparison with clinical data enabled us to esta-blish human tolerance DPT value for thoracic spinalcord up to 20 cm of lenth. Tolerance irradiationdoses of various regular schedules were calculatedfor practical use on the basis of DPT tolerancevalue. The DPT conception comprising explicitelytissue repopulation enables suggesting safe irradi-ation conditions in those cases where NSD or EDconceptions could lead to dangerous consequences.

Table 1 Radiation conditions for 5 fractions perweek (the part of results)

Fractions 5 10 15 20 25 30 35Total time 5-20 12-20 19 26 33 40 47/days/Total dose 24.2 32.1 37.7 43.6 49.3 54.8 60.0/Gy/

1. Kozubek,S., Vodvarka,P.: Late effects of fracti-onated irradiation of normal tissue. Neoplasma,1984, 31, 203-212.

269

THE TEMPERATURE CHANGES IN RABBITS AFTER TEMPO-RARY OCLUSSION OF URINARY BLADDER ARTERIESDURING THERMORADIOTHERAPYK.VOLENEC. M.JUKL. A.MICHL. I.VODICKA. B.RAMERTDepartment of Radiobiology of Medical Faculty,Charles'University, Hradec Kralov<5, CSSR.

Ligation of aa. vesicae cranial, was performedin the rabbits. Then the microwave heating using2,3 GHz generator was done and the time intervalswere registrated, in which the pre-set temperatu-re of 43°C was reached. For temperature monitoringthe miniature thermocouple probe situated in uri-ne bladder wall was used.The mentioned observation was done before and im-mediately after oclussion. Further observationwas done in 24-hour-lntervals.The results demonstrate an important role of bloodsupply for the rate of temperature reaching andindirectly determine an experimenta]ly inducedhypoxia.The study is completed with quantification ofblood flow in observed areas with radionuclidetechnique of Rb uptake.

27a

RADIOSENSITIZATION OF ASCITE TUMOUR CELLS BY METRO-NIDAZOLE IN DIFFERENT PHASES OF TUMOURS DEVELOPMENT.S. VORONINA

Institute of Chemical Physics,Academy of Sciences,Moscow, USSR.The radiosensitizing effect of metronidazole/HZ/

on ascite tumours of mice /Erlich ascite carcinomaand NKLy lymphosarcoma/ in the different phases ofgrowth was studied. The exponentially phase is las-ting .during the 4 days then there is the plateauon the curve of the tumour growth. MZ was injectedinto mice intraperitoneally, 30 min before irradi-ation, 1 mg/g, in the different phases of the tu-mours development. The number of cells with thechromosome aberrations /bridges and fragments inana- and early telophases in the first mitosis af-ter irradiation/ were the criteria of the radiosen-sitization degree.It was shown that beginning the fourth day after

the tumours inoculation, when ascite volume awas1-2 ml and number of cells was 0,2 - 0,7.10°, HZis showing the radiosensitising effect. The degreeof radiosensitization is not changed during thefurther growth of tumours. The polarographic deter-'mination of the pO2 level in the ascite tumourshave detected that beginning fourth day of tumourdevelopment the pO2 pressure is very low: 1,4-6,9and 0,8-2,2 mm Hg into the NKLy and Erlich tumours.

So the early phases of tumour development arecharacterized by the low On concentration, thereare the hypoxic conditions formed and possibilityof the enhancing of radiosensitivity by electron-afflnic compounds.

271THE EFFECT OF CHANGES IN INTRACELLULAR GLUTHATHIONE LEVEL ONRADIOSENSITIVITY

0. VOS AND W.S.D. ROOS-VERHEY

Medical Biological Laboratory TNO, Rijswijk (zh), The Nether-lands.

The intracellular content of glutathione (GSH) in HeLa cellswas reduced to about 9% by exposing the cells to 0.2% buthioninesulfoximide (BSO) at 37°C for 16 hr. Under these circumstancesthe non-protein bound thiols (NFSH) were reduced to about 50%.Exposure to glutathione esters (Puri and Meister, 1983, Proc.Natl. Acad. Sci. USA, 80, 5258) was used to increase the GSHlevel in normal and in GSH depleted HeLa cells. When clonoge-nicity was employed as a parameter for radiation damage, it wasfound that BSO treatment caused a sensitization with a factorof 1.1 under air and of 1.4 under nitrogen. Exposure of normalcells to 16 mM methyl- or ethylglutathione ester gave a smallradioprotection. Exposure to 16 mM GSH gave no protection at all.GSH depleted cells, when irradiated under nitrogen and exposedto GSH-esters, had the same sensitivity as normal cells irra-diated under nitrogen. Exposure to GSH-esters caused an increaseof the level of intracellular GSH. This means that GSH-esterswere able to increase the GSH level sufficiently to restore theoriginal radiosensitivity. Exposure to GSH itself had only par-tially this effect. When GSH depleted cells under nitrogen wereexposed to 16 mM cysteamine a radiosensitivity was observedsimilar to that of normal cells exposed to cysteamine. Thismeans that resistance is increased above the level of normalcells. No increase in GSH level was found in such cells. Thisindicates that cysteamine not necessarily protects by increasingthe intracellular level of GSH, but that it may protect by anincrease of its own level in the cells. Experiments with DEMas an agent used for intracellular GSH depletion in combinationwith GSH-ester treatment are in progress.

272

ELECTROPHORETIC MOBILITY OP ERYTHROCYTES PROMGAMMA- OR ALPHA- IRRADIATED RATS PROTECTED BYADETURO29ETS. VgAgggA. T. PANTEV, K. KUSOVA, N.I. RYZHOV,B.5. PHKDOkENKOInstitute of Roentgenology and Radiobiology,Sofia,Bulgaria; Institute of Biomedical Problems,USSRMinistry of Public Health,Moscow,USSR

The damaging action of high energetic heliumions and of gamma rays was studied in terms.of surface electric charge alterations induced in raterythrocytes by "in vivo" irradiation.The experi-mental design included radiomodification condi-tions. The findings indicated alpha- and gamma-rayexposures to produce quantitative dose-dependentchanges in rat erythrocyte electrophoretic mobili-ty (EM), these changes being more marked for alphairradiation. Adeturone pretreatment of the animalsenabled to maintain EM of irradiated erythrocytesat levels close to normal. The modifying effectwas more prominent in animals exposed to alpha partides. Supportive evidence was thus obtained thatthe EM test may be useful in radiobiology for as-sessment of radiation damage and the degree of ra-diation protection afforded.

273

LONG TERM EFFECTS AFTER THERAPEUTIC ADMINISTRATION OFDIFFERENT DOSES OF 224R 3 (THORIUM X ) +

R. R. HICK, H. SPIESS*, W. GO'SSNER

Abteilung fur Pathoiogie der GSF, D-8042 Neuherberg and*Kinderpoliklinik der Universitat, D-8000 Mlinchen, F. R. Germany

Severe late effects in humans following intraveneous in-jections of an aqueous mixture containing " 4 R 3 (peteosthor)have repeatedly been reported since 1956. These patients, nowfollowed by SPIESS and MAYS (study I) received amounts total-

" 4ing several millicuries of "4R a with injection spans up tothe year range resulting in alpha-doses to the skeleton ofless than hundred up to several thousand rad. As of 1984, 55cases of bone sarcoma (mostly osteosarcomas) out of 898 pa-tients were reported. All, or virtually al*l of these tumoursare ascribed to radiation, since only 0.2 cases would havebeen expected naturally. The distribution of tumour appearencetimes ranged from 3.5 - 25 yr, averaging about 10 - 12 yr.

Study II comprises 1501 ankylosing spondylitis patientsinjected with much lower doses of 224R 3 (mean 4.8/uCi/kg bodyweight; mean alpha-skeletal dose: 67 rad) than in study I, aswell as a control group of ankylosing spondylitis patientsnot treated with any form of ionizing radiation. Until now,three cases of malignant tumours in the skeleton have beenobserved compared to an expected number of 0.4 - 0.7 based ongeneral population statistics. A recent risk estimate (Proc.Symp. Neuherberg, 1984) from the data of study I predicts 5.8radiation induced bone tumours for the present follow-up time.No bone tumour occurred up to now in the control group. It is,however, notable that none of the bone tumours observed instudy II was an osteosarcoma and that 2 of the 3 skeletaltumours observed are tumours of the bone marrow. In the highdose group of study I only 1 out of 55 bone tumours has beenrelated to the bone marrow.

•••Supported by EURATOM Contract BI-D-461-D(B)

274

LIPOFUSCIN-LIKE PIGII3HTS TIME COURSES III ERYTHROCY-

TSS AND SPLEEN OP '.TOOLE-BODY GAKMA IRRADIATE1) RATS.

J.'Vilhelm

Faculty of Medicine,Char!es University,Prague,5o3R

Lipofuacin-like oigments - the end producta of

fr- e radicals attack on unsaturated lipida were de -

termined fluorimetrically in erythrocytea and spleen

of gamma irradiated rats (Co,6.87 Gy), 6h after

irradiation,and on the 3rd, 7th, 13th, 20th, and

23rd post-irradiation day.The initial increaae in

lipofuscin-like pigments in erythrocytes 6h after

irradiation was followed T>y a decrease to control

value on the 7th post-irradiation day, and from the

13th post-irradiation day their concentration in -

creased again. Lipofuscin-like pigments in spleen

followed a reciprocal pattern to that of erythrocy -

tea. It is suggested that irradiation-damaged ery -

throcytes were decomposed in spleen.Besides that

lipofuacin-like pigments time courses revealed di -

rect and indirect effect of ionizing radiation.

275

CYTOGENETIC INVESTIGATION IN PATIENTS AFTER

IRRADIATION OF THE SHOULDER*OOINT

G. WOLF, R. KAMMERER, H.FENDERS t a a t l i c h e s Amt fur A t o n e i c h e r h e i t und S t r a h l e n -echutz der DDR, B e r l i nMediz in ischs Akadenie Magdeburg, DDR

Per iphera l lymphocytes were examined for the I n -c idence of chromosome a b e r r a t i o n s in 10 p a t i e n t sbefore and after therapeutic irradiation of theshoulder-Joint. Treatment coneieted of 4 exposures(skin doee 12900 /vC/kg, X-rays), given in 2 fracti-ons a week. The field size was 10*15 cm. Lympho-cyte cultures were incubated 48 h and prepared ac-cording to the method of MOORHEAD et a l . (I960).Control data were derived from 8 healthy persons*During and after irradiation no significant in-crease in unetable chromoeoms aberrations could beobserved, but there was a highsr incldencs of di-centric chromosomes and acentric fragments in thepatients' group even before irradiation.Reasons for ths highsr frequency of chromosoae ab-errations may bs seen in the uee of antlrheumaticdrugs and other medicaments before and during i r -radiation treatment.

276

SODIUM ARSENITE INDUCES DNA STRAND BREAKS ANDINHIBITS DNA REPAIRF.H. YEW, P.Y.YEH AND L.M.CHANGDepartment of Zoology, National Taiwan UniversityTaipei, Taiwan, ROC

Sodium arsenite( IOJIM) when given to normal humanskin fibroblast cells(3hrs) causes DNA singlestrand breaks. Part of the sinle strand breaksare converted to double strand breaks after pro-longed incubation. In CHO cells the singlestrand breakscaused by arsenite are not apparent,but after HV irrar1iation( 10J/m2 ) arsenite( 10uM)inhibits DNA excision repair; double strand breaksare also generated after prolongedîncubation.The results lead to an understanding of molecularmechansm for synergistics of arsenite on UV andmethylating agents.

277

PHILOSOPHY OF DOSE-FRACTIONATION IN RADIOTHERAPY

Ji?£ Zamecnik.M.D.,Ph.D.,VLasta Mlejnecka,M.D.

Radiotherapeutical Institute,Prague,Czechoslovakia

The normal and tumor tissues respond differentlyto fractionated irradiation. On the basis of re-view of radiobiologioal data from the literatureand on own clinical experience on more than 8000patients treated with unconventional fraotionationregimens it has been possible to evaluate somelogical concept for clinical practice.Whenever unconventional fractionation scheduleis used the biological equivalent dose should beexpressed in terms of equivalent Gy. The endeffect of fractionated radiation treatment de-pends on the klnetio properties of the tissue(on the same dose level). The tolerance increaseswith hypofractionatlon in acutely respondingtissues, with rapidly turning-over cell popula-tion capable of rapid regeneration, with highreoxygenation capaoity. Such tissues on theother hand are more afflicted by hyperfractiona-tion and vice versa.With tumors the problem of dose per fraction ismore complicated as the kinetics of clonogencells is not only similar to the tissue of ori-gin, but changes^during the tumor growth (expo-nential and plato phase). With change in cellkinetics we have to ohange the fractionationschedule (dynamic or hybrid fraotionation regi-mens). Choice of strategy is easy if the cellkinetics of tissue at risk and of tumor is di-fferent.

278

Modification of radiation and radiomimetic ef-fects by interferons in human cells*

G.Zasukhina, W.Chekova, N.AlekhinaInstitute of General Genetics of Academy ofSciences of USSR, Moscow

It was shown that inoculation of the leuco-cyte interferon in human lymphocytes culture wasaccoraponied by reduction in the number of chro-uosorae aberrations and sister chroraatide exchan-ges (SCE) induced by fast neutrons and radiomi-metics. The kinetics of viability of cells nndanticlastogenic activity of interferons in humanlymphocytes was studied in the experiments withfast neutrons, gamma-radiation and 4-nitroquino-line-1-oxyde. The background of this phenomenonv.as the discovered capacity of interferons tostimulate the repair synthesis of DNA after mu-taênic treatment* The protective effect of in-terferons (criteria of SCB formation and repairsynthesis) was observed in cells of patiens withKarphan syndrome which were characterized by di-sorders of exscision repair*

279

THE 02 EFFECT ON REPARATION PROCESSES IN RAT BONEHARROB AFTER WHOLE-BODY IRRADIATION

JI.ZIHA, I

Radiobiology Department of Charles' University -Medical Faculty,

Hradec Kralove, C*SSR .

The cell numbers and the O2 tension / using a•odified polarographic Method / in the femur bone•arrow /BN/ of feaaleQrats after their whole - bodysingle irradiation / Co/ were studied in connectionwith the research into the reparation processes. Adecrease 1n the number of 8M cells observed threedays after exposure of animals to different dosesof ionizing radiation is represented by an exponen-tial curve/ while an increase in the 0- tension runsan opposite course. A hypothesis was aide that thedecrease in the nuaber of cells in BH of the feaurthe 0? offer Is higher than its consumption and viceversa? To verify this hypothesis, the "Split Dose"Irradiation technique at time intervals of 1-3-7-15days and the above Mentioned methods were used. In•II irradiation doses I/6+3/Gy; /4.5 t 4.5/Gy; /3+•6/6y| an Increase in the nuaber of cells in BN wasevident froa the 7-day interval while a decreasewas shown in the 0- tension. The parameters studiedwere slightly improved by stay of the experimentalanimals after irradiation in the atmosphere.

280

SMALL-ANGLE X-RAY SCATTERING STUDY ON THE INFLUENCE OFADDITIVES ON THE X-RAY INDUCED AGGREGATION OF THE SULFHYDRYLENZYME MALATE SYNTHASE

P.ZIPPER, M.KRIECHBAUM, R.WILFING, H.PURCHSCHLAG

Institute of Physical Chemistry, University of Graz, Austria,and Institute of Biophysics and Physical Biochemistry, Univer-sity of Regensburg, FRG

The method of small-angle X-ray scattering (SAXS) has beenintroduced by two of us as a novel technique for studying radi-ation damages of biopolymers (P.Zipper, H.Durchschlag, 1980,Radiat.Environ.Biophys. J[8.»<>9). Recently we performed SAXS in-vestigations of the damage of malate synthase X-irradiated inaqueous air-saturated solution in the absence or presence ofvarious additives: formate, superoxide dismutase (SOD), cata-lase, NaCl, substrates (acetyl-CoA, glyoxylate) and analogues(malate, pyruvate, ot-ketobutyrate, oxaloacetate, glycollate,lactate). Measurements on samples pre-irradiated with 6 kGy inthe absence of additives revealed the occurrence of considerableaggregation and fragmentation; the presence of catalytic amountsof SOD and/or catalase reduced aggregation significantly; thepresence of formate during irradiation led to a strong decreaseof aggregation and fragmentation. These results are confirmed bystudies in which the radiation damage of samples during pro-longed SAXS experiments was monitored in situ by means of SAXS.All above mentioned additives impeded aggregation, however to adifferent extent; pronounced effects were registered for for-mate, substrates and analogues. Our results suggest that bothscavenging and specific protection are involved in the protec-tion mechanisms against X-ray induced aggregation of ablate syn-thase.

281

CAN ACTION SPECTRA PCJR INaCnVKTION AND MOTAGENESIS INCHINESE HAMSTER CELLS BQT USED TO PREDICT THE EFFECTS OFRDLYCHHOMflTIC RADIATION?

F. ZOlzer, J. KieferStrahlenzentrum der Justus-Liebig-Uaiversitat, Giessen, FRG

If action spectra are of any use for risk estimates/ theyshould allow to predict the effects of polychromatic radiation.Originally we set out to investigate the wavelength dependenceof inactivation and nutation induction to 6-thioguanine-resi-stance in V79 Chinese hamster fibroblasts (Photochem. Photo-biol. 40 (1984), 49). Our results agree quite well with thosereported by Hothman and Setlow (Photochem. Photobiol. 29 (1979),57) for the inactivation and dimer formation in the same cells.

Both sets of data were then compared with others obtainedby Zelle et al. (Mutat. Res. 72 (1980), 491) applying two dif-ferend kinds of polychromatic radiation to Chinese hamsterovary cells. To this end the action spectrum for a given effecthad to be multiplied with the emission spectrum of the radiationsource in question. Such calculations predicted dimer formationquite well, but considerably underestimated the lethal andmutagenic effects of polychromatic radiation. We suggest,therefore, that the different components of polychromatic ra-diation act independently with respect to dimer formation, butsynergistically with respect to cellular effects.

These investigations have now been extended applying simu-lated sunlight of different spectral composition to our ownV79 fibroblasts.

282

FUNCTIONAL STATE OF THE RAT THYROID GLAND DETERMINES ITSRADIOSENSITIVITYM. ZWITTER1, M. KALISNIK2, M. LOGONDER-MLINSEK2A O

Institute of Oncology and Institute for Histology andEmbriology, Ljubljana, Yugoslavia

An animal experiment has been designed to evaluate a pos-sible influence of the functional state of the thyroid on itsradiation sensitivity. According to the procedure prior to ir-radiation, 79 male Wistar rats were divided into perch!orate(stimulated), thyroxine (suppressed), and control groups. Theneck area was then irradiated with X-rays, 55 kV, and subgroupsof animals were given single doses of 0, 1.5, 3, 6, 12, and 18Gy,respectively. Proliferation in response to goitrogens, asensible test of the reproductive integrity of thyrocytes(Crooks et al, Br J Radio! 37:380, 1964) was used to asses theradiation damage of the thyroid. One month after irradiation,drinking water was replaced by 1.2J> solution of Na-perchlorate.Animals were killed 3 months later. After careful preparation,thyroids were weighted and then processed for histology.

Irradiated thyroids were smaller than those given sham ir-radiation only. On the microscopic level, morphometry showedmore interstitial tissue, smaller follicles, a greater percentof disrupted thyrocytes, and a smaller epithelium/colloid ratioin the irradiated glands. These changes were progressive as thedose of irradiation was increased. The quantity of interstitialand fibrotic tissue, and the percent of disrupted thyrocyteswere smaller in the irradiated animals of the thyroxine group,as compared to the other two groups.

Further long-term experiments will be necessary before adefinite conclusion can be reached. Nevertheless, our resultsdo provide an experimental support for the idea that suppres-sion of the thyroid might reduce the radiation damage to thegland - a frequent finding in patients after irradiation forthe head and neck cancer.

283

DECAY OF THERMORADIOSENSITIZATION IN THE R1H TUMOURAFTER COMBINED TREATMENTS WITH X-RAYS AND HYPERTHER-MIA

F. ZYWIETZ AND H. JUNG

Institute of Biophysics and Radiobiology, Universityof Hamburg, D-2000 Hamburg,, F-R.G.

The increase in tumour radiosensitivity by adju-vant hyperthermia was studied in the R1H rhabdomyo-sarcoma (H. Jung et al. 1981, Europ. J. Cancer 17,375) transplanted in the flanks of syngeneic rats.Heating was performed using a temperature-controlledmicrowave system (F. Zywietz et al. 1983, Strahlen-therapie 159, 386). When a h«at treatment at 43°Cfor 60 nin was given immediately after a single doseof 15 Gy, tumour growth delay increased from 8.3 to17.2 days corresponding to a thermal enhancementratio of TER = 2.1. After combining 30 Gy with hy~perthermia, a TER = 1.7 was obtained. Fractionationover 2 or 3 weeks reduced the sensitization ratiossignificantly. - In order to study the temporaldisappearance of thermoradiasensitization, irradi-:ation and heating were separated by time intervalsranging from 10 min to 4 hrs. Tumour growth delaydecreased with increasing time interval and approa-ched the level of additivity after 30 min indicatingthat in the experimental system used, radiationeffects may only be enhanced by hyperthermia if thetwo modalities are applied within a short timeinterval.

2#4

A 2 * * *

285

METABOLIC BEHAVIOUR OF PLUTONIUM IN MICE

U. Andreozzi, L. Addis, M. Garbati, A.'Lori, A. Minnucci,

Laboratorio Tossicologia,

M. Castprina,

Serv. Studi.ENEA, CRE Casaccia, 00060 Roma, Italy.

Some 2500 CB3F1 3 month old male mice have been injected

endovenously with 0.2 ml citric solution of 239-plutonium. The

range of activity injected was 0.044-4.4 kBq/kg body weight,

in 6 groups with 300-500 animals per group. Over 600 animals,

divided in 7 groups, were taken as age matched controls.

This experiment was performed to evaluate the distribution

of 239-plutonium in our mice strain at vepy low contamination

levels and to correlate the absorbed dose to the skeleton

for the induction of bone tumor.

Radiometric results are presented to show the plutonium

biological retention in the skeleton; The skeleton retention

curves do not exhibit any differences among the injected

groups receiviig plutonium with a factor up to 100 as far as the

activity level injected is concerned. Cumulative mortality cur-

ves of treated animals referred to control groups are also

presented, to evaluated possible life shortening effects.

286

LIPOXYGENASES IN MODIFICATION OP PLANTRADIATION DAMAGEI.O.BORISOVA ,E.V.BOUDNITSKAYAA.N.Bach Institute of Biochemistry ,USSRAcademy of Sciences , Moscow , USSR •

It is shown that the role of Lipoxygenases( LOXs ) in developing radiation damage inplants is determined by participation of theseenzymes in reactions of plant cells recoveryfrom ionising radiation •The study LOXs activity , their intracellularlocalisation and the isoenzyme composition inthe normal state and in different period atterirradiation in vivo and in vitro in dosesfrom 5 to 1000 Gy showed their high radioresis-tance , D37 500 - 3000 Gy .Reversible activation of LOXs in the erlierpostradiation period after irradiation usingsublethal doses from 5 to 100 Gy may be due torecovery of biomembrane lipids and their func-tions •Irreversible activation of lipid peroxide reac-tions in plants after irradiation in lethaldoses C up to 1000 Gy ) is caused by intracel-lular changes in the LOXs localization , accu-mulation of free polyunsaturated fatty acidsand their peroxides , which leads to intensi -fied development of plant radiation damages •

287

EFFECT OF LIPOXYGENASES MOLECULAR ORGANISATIONON THEIR RADIATION INACTIVATION

I.G.BORISOVA , E.V.BOUDNITSKAYA , G.L.SHAPOSH-NIKOV , V.V.SHOUBIN

A.NoBach Institute of Biochemistry , USSRAcademy of Sciences , MoscoW , USSR ,

The action of ionizing radiation in vitro indoses from 10 to 1000 Gy on the activity andcomposition of multimolecular forms of lipoxy-genases (LOXs) has been studied .Analysis of the amino acid composition and se-condary structure of LOXs with CD and IR-spec-troscopy allowed us to reveal some differencesin the molecular organisation of LOXs from ce-reals and legumes and their influence on theextent of radiatioxi inactivation of these en -zymes. It is shown that the LOXs inactivationafter irradiation in lethal doses is due topostirradiation changea in the amino acid com-position and in the secondary structure of theenzyme molecule, A decrease in the LOXs cataly-tic activity in legumes is observed v/hen thetryptophane content decreases.Inactivation of the wheat LOXs is not accompa-nied by any changes in the amino acid composi-tion but is dependent to a greater extent onradiation damages of the enzyme secondary stru-cture as compared with that of the LOXs fromlegumes .A high radioresistance of the wheat LOXs (D372000-3000 Gy) and the LOXs of legumes (D37 500-1100 Gy) allows us to consider these enzymesystems as important endogenic regulators,res-ponsible for development of postirradiationdamages •

288

SOME MECHABISMS OP THE RADIOPROTECTOfi

EFFECTS OF CISTJUCEHE.S.Cabarielian, S.A.3adjinian, S.E.Bako-

po-vr, A.A,Kharati«n

S.I. Sec tear of Radiobiffllogy M.o£ Care ofPublic Healtfc, USSB, Armenia., Ejnevani

It is arranged that voder tha action of cista-min ocsitriptamin is released, connected with. theintravascular unit of Itronibocita. Simultaneously adiminution of the plasmatic alTatunin abilities is ob-Bearved. These effects at the cistamin are observedonly in vit»o not in ritro.

It ia suggested that this phenomenon, in somemeasure, mediates the radiomodifing effects of cie-tamin, owing to the increase of the free forms ofbiogeneamina in blood» An analogous reaetion oftrombocit release is also oAttsexved in the earlj pe-riods of tiae irradiation. The last circumstance mayplay a definite part in the pfcenomemoxt of the endo-genous radioresistance a organism. The analysis ofthe mechanisms of the present phenomenon shows thatthe release of the granulation apparatus, which thetreabocits contain, ia connected with tike partialdepolarigation of their diaphragms (membrans) and-the physico-chemical property changes, odf their mat-rik.

289

COMPARISON OF THE EFFECTS OF X-RAYS AND FAST NEUTRONS ON THECYCLE DURATION OF EMT6 CELLS. A TIME-LAPSE CINEPHOTOMICROGRA-PHIC STUDY.J.GUEULETTE, M.BEAUDUIN, Y.GALIANO de BULA and A. WAMBERSIE

Cliniques Universitaires St-LUC, UCL, 1200 BruxellesHopital de Jolimont, 7160 Haine-St-Paul (Belgium)

The time-lapse cinephotomicrographic technique was usedto compare the cell cycle duration lengthening resulting from250 kV X-rays and fast neutrons irradiations. The neutrons areproduced at the cyclotron "CYCLONE" of Louvain-la-Neuve by bom-barding a beryllium target with 65 MeV protons. Exponentiallygrowing EMT6 cells were exposed to increasing doses of radia-tion at the moment of their 3rd generation (48 h after trypsina-tion). The pedigree and cycle duration of each cell were deter-mined by following its divisions on a TV screen after the filmshave been transferred on video tapes. In order to facilitatethis analysis, the real time (hours, minutes) as well as thetemperature were simultaneously printed on each microscopicalframe at the moment of shooting by means of an "optical incrus-tation system".

The median cycle duration of unirradiated cells is equalto 9.68h and remains constant during 5 generations in our cul-ture conditions. After X-rays, the median cycle duration of theirradiated generation reaches 10.77 , 12.95 , 14.95 , 16.15 and20.25 hours for doses of 1, 2, 4, 6 and 8Gy respectively ;after neutrons, it reaches 11.23 , 13.40 and 15.13 hours fordoses of 0.75 , 1.5 and 2.5Gy respectively. If one assumes thatthe corresponding mitotic delay is a linear function of the do-se, it.can be evaluated equal to 1.15h/Gy for X-rays and to2.30h/Gy for neutrons, which leads to a neutron RBE value of =2.

The RBE obtained for this effect is less than that obser-ved for lethality at low doses up to 2Gy (RBE-2.6 - 2.8). Thisdifference involves a difference in the redistribution of irra-diated cells which suggest a qualitative difference between thetwo modalities of irradiation.

290CHROMOSOMAL RADIQSENSITISATION OF NOBMOXXC ANDHTPOXIC CELLS BY MISONIDAZOLE, VLADILRAD ANDOTHER E1ECTR0NAFFINIC COMPOUNDSST.IMB8H C. VLADBSCU ADBLA BABA PIROSKA IMHEH

Inet. of Medicine and Pharmacy, Lab.RadiogeneticaCluj-Nspoca, Romania

In mouse Ehrlich aseites cells artificialhypoxia was induced by aacrification of carrieranimals /cervical dislocation/ 3o min. before irra-diation. After 24 h in vitro cultivation of asci-tea cells, Misonidasola and Vladilrad /electronaf-finic adjuvants of radiotherapy/ were both signifi««cant enhancers of micronucleus frequency and in-hibitors of mitotic activity.

In normoxic cells however both products wereonly additive agents.

The electronaffinic compounds hydroquinoneand metil aminophenol sulphate were both effectiveenhancers of radioinduced cell killing in anoxicconditions.

Metabolites like para aminobensoic acid andfolic acid as well as the acidic environment crea-ted by ascorbic acid, decreased the claetogenieeffect of radiation and above mentioned compoundsand were mitotic stimulants after radiation*

This protective tendency against the actionof electronaffinic radiosensitisere was observednot only in micronucleus analysis but also in theQg yield of chromosome aberration analysis*

291

EXPERIMENTAL DETERMINATION OP- /d,n/ NEUTRON'S DOSEDISTRIBUTION IN RATSS.JEDNOROG, B.ZAZASKAMilitary Institute of Hygiene and Epidemiology,Warsaw, Poland

.he aim of this work was to determine the distri-bution of neutron dose•absorbed by the body of ratand its phantom. As a source of high energy neutronradiation a cyclotrone U-120 therapeutic unit wasutilized. The measurements of absorbed dose werecarried aut with use of tissue-like ion chamber andthe results were areraged numerically according tothe linear regression method. With both the animalbody and its phantom a 40 percent decrease ofabsoerbed dose was found along the beam axis anda close to symetrlcal distribution of the doseperpendicularly to the.beam. The results indicatethe usefulness of phantom for determination of thedistribution of absorbed dose within the body ofrat.

2 9 2

CYSTEINE PROTECTION AGAINST THE RADIATION-INDUCED BINDING OF OXYGEN TO ENZYME MOLECULESIN SOLUTIONL.I. KHARCHENKO, T.E. PAVLOVSKAYA

A.N.Bach Institute of Biochemistry,Moscow,USSR

The effect of radioprotective compound - cys-teine - on the quantity of oxygen bound to al-cohol dehydrogenase (ADH) induced by ionizingradiation was being studied. The agueous enzy-me solutions were irradiated with "^Co gamma-ray* (1000 Gy) in oxygen enriched with a stableI8o isotope. The 1^0 content was mass-spectro—metrically measured. Irradiation of ADH resul-ted in the binding of 12.9 oxygen atoms perADH molecule which retained 50S& of its activi-ty. Then the ADH solutions were irradiatedwith a cysteine:ADH molar ratio 1:140. Mass-spec trometrically tests were performed with-out seperated cysteine and ADH molecules.The presence of cysteine diminished the oxy-gen binding up to 7.4 oxygen atoms calculatedper ADH molecule+140 cysteine molecules, theenzyme activity almost completely retaining.The perturbance of the enzyme molecule ctruc-ture was also estimated. On the basis of theresults obtained we suggested that one of themode of the protective cysteine effect underirradiation, with the respect to enhancingaction of oxygen, should include the bindingof oxygen to cysteine molecules.

293

LUNG AND SKELETON MALIGNANT TUMOUR INDUCTIONDUE TO HIGH LET oC-EMITTERSE.R. LYUBCHANSKY, L.A. BULDAKOV. Z.M. BUKHTOYAROVA,R.A. EROKHIN, T.I. LEVDIK, V.K. LEMBERG,N.A. KOSHURNIKOVA, A.P. NIPATOV, E.G. SINYAKOVInstitute of Biophysics, Ministry of Health,Moscow, USSR.

Histologic and radiometric examination was car-ried out in 5,900 and 10,150 rats with 715 cases oflung tumours (LT) and 830 osteosarcomas (OS), res-pectively, following inhalation or parenteral in-fection of 7 soluble compounds of 237Np, 23 9Pu, and24 lAm.

Spontaneous LS? occur in 0.4% of rats, while do-ses of 25; 61; 117; 234 cGy result in LT in 1.7;3.4; 4.5; 8% of animals, an excess being describedby the equation P(%)-0.094D°»803. With dose increa-se to 435; 914; 1516 cGy LT incidence grows to 21;25; 18* against average life span shortening by 7;23; 44*, respectively. Absorbed doses of 0.07-6 cGybring about a 3-fold increase of LT among 15 out of918 rats.

Doses to the skeleton of 5; 14; 30; 60; 120; 218;430; 840; 1800 cGy result in OS occurence in 0.7;1.3; 2.9; 3.3; 7.3; 11.7; 13.7; 20.2; 22.5% of ani-mals. At low doses OS incidence is 0.11% per 1 cGy,over the range of 30-218 cGy it is determined fromP(%)-0.192D0#78\ and then drops by a factor of 5, apossible reason being a killing effect of ©C-radia-tion (Buldakov L.A. et al. - In: "Radioisotopes andOrganism". Moscow: Meditsina, 1969, pp. 285-291).

Thus, at permissible levels of occupationalexposure of 15 and 30 cSvyear""1 LT and OS risksover 50 years are 1.8 and 1.5%»not differing great-ly from the ICRP Publ. 26 assessment - 1.5 and0.75%.

'294METABOLICAL MODIFICATION OF HAEMOPOESIS DAMAGEDURING RADIATION DISEASEO.MAKIEJKVMedical I n s t i t u t e , Sverdlovsk, USSR

The character of the p o s t r a d i a t i o n compensationi s depend on the degree and haemopoesis r e a c t i o n ,and the l a s t one r e g u l a t i o n during extermal a f f e c te s s e n t i a l depend on metaboletes forming in the 'or -ganism during the damage.

The item of this research was to investigate the.influence of metaboletes forming In the organismduring the extermal affects: succlnic acid, ^-na-trium oxibutirati, inosini on processes of thepostradiation haemopoesis restore. During six t i -mes repeated infusion to the CBA mice of the au-ccinic natrii ,^-natrium oxibutirati, inosini (at40 mg per kg of mass once a day) and one time Jf-radiation (4 Gr) the increasing of blood leuoocy-tas ' s quantity and bone marrow's lyaphoid ce l l swas observed (at 19, 30, 33%6 accordingly). Thebone marrow's nuclear ce l l s quantity i s increasesalso (at 22, 30, 48%%). That i s testyf ies haemo-poesis bridge-head increasing. The quantity of co-lony forming unites (CFUc) are increasing simul-taneously (at 79, 130, y?%%).

The infusion of investigated metaboletes to bo-ne marrow's rec'epie&tts on the background of in -troduced bone marrow7s c e l l s before and after le-t a l radiation showes the increasing of the CFUcnumber and spleen's colony forming act iv i ty ,that's testyf ies metaboletes abi l i ty of IEK chan-ging* In the following experimentes was shown theincreasing (activation) of prostaglandin's andadenilat-cyclise's syntheses systeaes during meta-boletes's level increasing. This i s the way aeta-boletes real ises tbair radiotherapeatic influence.

295EJFBCT OP IRRADIATION ON PROTEIN AND LIPID COMPOSI-TION OP NUCLEAR AND MITOCHONDRIA! FRACTIONS OP RAB-BIT EMBRYO LIVER.

A.K.MIRAKHMEDOV.M.M.DJURAEVA.D.EH.KHAMIDOY.

Institute of biochemistry of the Academy of Scien-ces of Uzbek SSR, Tashkent, USSR.

The effect of irradiation on phospholipid content

and activity of lipid-dependent enzyme Mg +- ATPase

in isolated nuclei and mitochondria of rabbit em-

bryo liver was studied.Irradiation in the dose of

1,86Gr was carried out on 20,23 and 30 days of

intrauterine development,the studies were made wi-

thin 1hr and 24hrs after irradiation.Membranes phos,

pholipid content of liver nuclei and mitochondria

raises at the begining of fetal period raises, whe-

reas at the end of development the irradiation pro-

duces a drop in their amount up to 30% in nuclei wi-

thin 24hrs, and in mitochondria up to 5OJ6 within

1hr.Irradiation exerts a pronouced activating in-

fluence on the Mg 'ATPase in all studied periods of

development,the greatest increase of enzyme activi-

ty is observed in nuclei on 23 day of development.

Analysis of date leads to a conclusion that phospho-

lipid content and Mg -ATPase activity of nuclei and

mitochondria of rabbit embryo liver show similar

sensitivity to the action of radiation.

296

PHOTOSENSITIZATION TO NEAR-ULTRAVIOLET LIGHT BY8-METH0XYPS0RALEN IN THE CHINESE HAMSTER CELLS INVITRONGUYEN HUU DONG and MAKpONOV fi.P*Centre of Agricultural Genetics, Hanoi, Vietnam,Institute of General Genetics, Academy of Sci.Moscow, USSR

In this work photosensitization to near-ultravio-let light by 8-METHOXYPSORALEN in the Chinese Ham-ater cells in vitro was studied. The results showedthat the effects of monoadducts anc diadducts forinduction of chromosomal abberatione were the same,while interstrand crosalingkages induced more chro-mosomal abberations than monoadducts. Analysis ofspectrum of chromosome abberations showed that du-ring transformation of monoadducts into diadductseffects of inducing the abberations of chromosomeswere different for these primary damages in thecomplementary strand.

297

THE USE OF GAMMA RAYS IN RICE BREEDING FOR COLDTOLERANCE

NGUYEN KIM HAICentre of Agricultural Genetics, Hanoi, Vietnam

In Vietnam two crops of rice can be grown withina year: the first crop ("Spring Rice", from Decem-ber to June) and the second crop ("Summer Rice",from June to November). Temperatures below 15 Care frequently registered from November to March inNorth Vietnam. Therefore the breeding of cold tole-rant rice varia-ties is of a great importance.

Seeds of rice varieties IR 8, IR 9575, CR 203,Bellardon, Bau, Cut, Cuont and Saiduong were exposedto different doses of gamma rays: 10, 15, 20 and30 kr. Some of the rice mutants obtained yieldedmore than their parents} five of them appeared tobe more resistant to low temperature. The importedvarieties susceptible to cold (IR 8, IR 9575 andCR 203) gave more mutation spectrum and frequencyas compared with the relatively cold-resistantlocal cultivas (Bau, Cut, Cuom), but from the latterit has been established more cold-tolerant mutantsthan from the former.

298

CONFORMATION CHANGES OF BLOOD PLASMA PROTEIN MACBO-MOLECULES OF RATS AFTER THE COMBINED ACTION OF sySrOR i4*Ce and PHOSALON2. Paskalev, I. Pejankov, E. Hadjidekova -Institut of Roentgenology and Radiobiology, SofiaBulgaria

Experiments are carried out on rats "Vistar" trea-ted with the combination of 89-Sr (per os in activi-ty 370 kBq) or 114-Ce (i.p. in activity 133.2 kBq)and phosalon (1/60 of LD5O/3O).

Conformation alterations of rat blood plasma pro-tein macromolecules are determined from their die-lectric constant frequency dispersion.It is settled that radiation causes prolongation

of the macromolecules, phosalon provokes packingtheir globular conformation. The combination phoaa-lon - radionuclide increases conformation changesof plasma macromolecules in comparison the self-in-dependent effect of the two factors and the degreeof these changes depends of time after the combinedapplication of these factors.

299EFFECT OF RADIATION AT EARLY STAGES OF ONTOGENESISIN PLANTSPMAN PHAICentre of Agricultural Genetic*, Hanoi, Vietnam.

A* original technique has been development oftreating gametes, tygotes and early embryos of Ni-gel la, Rice and Soybean with gamma radiation. A de-lay in fertilization and a decrease in the rate ofcell division of the embryos and the endospermsafter the mutagen treatment hare been found* Ourmethod of treating gametes, sygotes and proembryoswith physical mutagen is, by all criteria, superiorto that of treating dry seeds. Treatment applied atearly stages of ontogenesis not only induced a muchhigher mutation ratio compared with dry seeds, butalso gave a broader mutation spectrum. The 87 typesof hereditary changes Obtained affect the structureof vegetative and reproductire organs. Mutationswhich change the structure of the reproductiveorgans of flowers are of specific interest.

300GENETIC EFFECT OF PHYSICAL MUTAGEN IN SOYBEANPHAN PHAI and DINH LUYENCentre of Agricultural Genetics, Hanoi, Vietnam

Seeds of 7 varieties of soybean (Soja max) DT 75,VkK, CLN, DBSCL, DT 70, DT 74 and DT 94 were trea-ted with gamma rays. The effective doses for muta-genic induction were 5, 10, 15 and 20 kr, the op-timal doses were 10-15 kr.All cultivars used in the experiments showed spe-

cific reaction to the mutagen reagents. After themutagenic treatments a great number of mutants we-re obtained, some of which were dwarf or of earlymaturity, high productivity, high protein contentand could be used for selection. From the selectedprogenies two mutants were established: PM 70-81,a dwarf mutant resistant to diseases, its seedyield was 2.2-2.5 ton/ha, and PM 47, a giganticone, its seed yield was 2.2-2.8 ton/ha and yieldsof over 3.5 ton/ha have been produced in smallacreages, while the control plants yielded only1-1,2 ton/ha.

301EFFECTS OF LOW DOSES RADIATION OF GAMMA RAYS ONGROWTH AND DEVELOPMENT OF CULTIVATED RICEFHAN PHAI and TRAN DUY QUYCentra of Agricultural Genetics, Hanoi, Vietnam

Dry seeds (14 o/o humidity) of three rice varie-ties (IR 22, IR 8, C4-63) were irradiated with gam-ma rays at doses of 200, $00, 800, 1000, 1200 and1500 r.

No essential alterations were found in the samp-les exposed to 200 and 500 r radiation. The dosesof 800, 1000 and 1200 r were shown to stimulategrowth and development of all the three varieties*Especially the 1200r-treated samples yielded 15 o/ohigher as compared to the control. The dose of 1500r induced chromosomal aberrations in the rice meris-tem cells and caused little seedling injury withsubsequent reduction of seed yield and, thereby,possessed a mutagenic affect.

302THE USE OP GAMMA RADIATION IN BREEDING AND IMPRO-VEMENT OP RICEPHAN FHAI. TRAN PUT QUY and VU DUC QPANQCentre or Agricultural Genetics, Hanoi, Vietnam

A comparative study of mutagenic effects of gam-ma rays at different doses (5 to 35 kr) has beencarried out on dry and germinating seeds of 10 lo-cal and imported rice varieties. Various morpholo-gical and physiological changes and chromosomalaberrations observed in the rice plants were evalu-ated. The doses of 15-2? and 5-10 kr were found tobe the most effective for inducing mutations in thedry seeds and the germinating ones respectively,irradiation of the latter having more mutageniceffects as compared to the former.Hundreds of mutations suitable for rice improve- \

ment-were selected in the M.-M6 lines. These were •dwarf, hard stems, straight leaves, high seed yield,high protein content, adaptation to deep water, re-sistance to disease etc; The mutants 250 and NN2298 have took the first and the third places inthe State Rice Test Station as high-yielding sum-mer rice varieties resistant to diseases and adap-ted to deep water.

303M0RPH0METRIC STUDY AND EVALUATION OF HETEROGENEITYOF SOME INDICES OF ENDOMETRIUM HYPERPLASTIG PRO-CESSES AND CANCERL.Z. POLISHCHUK, Y.G. TIMOSCHENKO^R.E. Kavetsky Institute for Oncology Problems Ukr.SSB Academy of Sciences, Kiev, USSR

On histological preparations of endometrium dia-gnostic scrapings of 5» patients with disfunctionalmenorrhagia a morphometric study of endometriumglandular component including a measuring of glandsperimeter and area, their lumens, epithelium rings'area, distance between glands, a computing of coef-ficients of a form with certain contours was carri-ed out. Thfe given task was realized with the aid ofsemi-automatic divice on the basis of. a computingcomplex using "KAMAK" equipment! and coordinatometer"Contour"• Software was worked out Within the îmiteof operating system "Rafoe". Using U.I.Petunin scriterion (1984) was aimed for estimation of hetero-geneity of indices under study.

The carried-out investigation has shown heteroge-neity of morphometric indices of endometrium cancsrand variously marked hyperplastic processes of endo-metrium. Besides, a quantitative estimation of poli-morphiam of studied morphologic indices has been ob-tained, which is essential for defining a prolifera-tion level in endometrium* Presented data are signi-ficant for the differential diagnosis of pretumorand tumoral processes in corpus uteri and for theselection of patients to mallgnization risk-group.

304

CHRCUOSOUE ABBBRATIOHS AND MICBOJUCLBI AS A TOOLFOB THE GEHETIC COUNSELLING IM 1*EDICAL RADIOLOGYP. RAJX7LBSCU, SI, IMHEH, ELISABBTA FAZAKAS

Inst. of Medicine and Pharmacy, Lab.RadiogenetissCluj-Ifapoca, Romania

In medical radiology the necessity of geneticcounselling appears: 1. in therapeutic irradiationwith impossibility of gonadal protection, in pro-creative agej 2. in diagnostic exposition of gona-dal mone shortly before fecundation,

1. In 25 patients treated with X radiationsfor ankylosing spondylarthritis, the frequency ofunstable chromosome aberrations decreased from9*26 to o.lo in 5oo days and remained unmodifiedfor 4 more years. These peripheral blood lymphocytedata are in agreement with the results of Edin-burgh group /Buckton,198V, and suggest that gene-tic counselling can be based on the cytogenetiecontrol at 18-24 months after the end of radio-therapy.

2« In le patients irradiated in the course ofhysterosalpingsgraphy /HISA/« 15 mQy by TLD doii-metry in vaginal bottom, neither the chromosomalanalysis nor the micronueleus one in lymphocytecultures revealed any increase of aberrations.However, in nice irradiated with logaritmic mul-tiples of HISA doses in a hip phantom in ovariantopography, a significant increase in bone marrowmicronueleus frequency was recorded starting withthe doubled dose of HISA /o.24 versus e.l? incontrols/* We suggest therefore that phantom mo-delling can be useful in every diagnostic radiolo-gical procedure where gonadal protection isincomplete or impossible and procreation isimminent*

305

EPPECTS OF AET AND ITS RELATIVE OR ANALOGICALCOMPOUNDS ON THE LEVEL OF ENDOGENEOUS RADI0SENSIT2-ZERS.STOEV. Tu.B.KUDRYASHOVInstitute of Roentgenology and Radiobiology,Sofia,Bulgaria»Moscow State University,USSRThere are established the radioprotective charac-

teristics of AET,of the product of its metabolism-2-amino-2-thiazolin(2-AT; and of the radioprotec-tors:2,4—diaminothiazol(DAT),2-amino-4—oxi-thiazo-linC^-OT^bromethylisothioroniCBETâdeturoneCasaltof AET and ATP),as a mechanical mixture(MM) of AETand ATP in equimolar quantities and,on the other side,of adenozine-threephosphate acid(ATP),in a rela-tive aspect in experiments carried out on mice.The effects of the radioprotectors on the quanti-

ty on the lipid peroxide products(LPP),consideredas endogeneous radiosensitizers is defined in or-gans and tissues.The data indicate the most valuab-le decrease of the LPP quantities,concerning the radioprotective time limits,in case of the applica-tion of the most effective radioprotectors DAT,ade-turone and AET by a DRF as follows 1.67»1.45;1.45.The effects of all the other substances is relatively lower when applied separately,ATP does not in-fluence the level of the LPP.The difference in theeffects of adeturone,AET and MM(equal basic AET content) as well as the lack of effect of ATP in theLPP indicate that ATP potentiates the effect of AETis case it is as a structural form of adeturone,probably due to another mechanism of action.The application of some radioprotectors on mice

in definite time limits results in a decrease ofthe level of endogeneous radiosensitizers(LPP),res-pectively, to their radioprotective action,when theorganism is accommudatied to a more radiosensitivecondition.

306

COMBINED ACTION Of LEUCOTHOFIflA, RADIATION ANDANTICANCBR DRUGS ON CHROMOSOMES AND MICRONUCLBIA.VALEAMU ST.IMREH Z. URAY M. COVALCIC

Inst. of Medicine and Pharmacy, Lab.RadiogemticsCluj-Napoca, Romania

In vivo /mouse bone marrow micronucleus teaVand in vitro /human neoplastic eell line, HeLa/experiments were performed to ascertain whetherthe chromosomal effects of cytostatic drugs mightbe influenced by a polypeptide complex of thymicorigin /Leucotrofina ELLEM/.

As model anticancer drugs, chromosome claa-togens mitomycin-C and cyclophosphamide, antime-tabolites 5-fluorouracil and methotrexate andspindle poisons, colchicine and vinblastine wereselected. 22o kV X-rays served as positive cont-rol or potentiation factor.

The lack of radiation or/and chimioprotectionin radioinjured hemopcietic bone marrow /micro-nucleus test/ shows that Leucotrophina /i.p./ isacting at supraehromosomal level.

In vitro however /in HeLa cells/, Leucotro-fina is a potent anticlastogen in combinationswith mitomycin-C, cyclophosphamide and methotre-xate, both on 0. chromosome aberrations and onmicronucleus production. Spindle poisoning isunaffected by Leucotrofina and/or radiation.

The fact that Leucotrofina is acting onOTA antimetabolites even in the G. of the cellcycle suggests a very specific effect on SNArepair synthesis.

A NEW MICRODOSIMETRIC APPROACH TO THE"ASSESSMENT OF CELLRESPONSE TO LOW .LEVEL EXPOSURE OF IONIZING RADIATION

J. BOOZ*, L.E. FEINENDEGENInstitute of Medicine, KFA JGlich, FRG

This paper describes a microdosimetric approach to the problemof radiation response by which radiation quality appears asthe consequence of two related probabilities/, that of energydeposition in the cell nucleus and that of energy depositionin DNA. The starting point of this paper is a "gross sensi-tive volume", identified with an average mammalian cell nu-cleus and structurized with smaller sensitive volumes, identi-fied with some critical parts of the DNA genome. This thenleads to the definitions of an "elemental dose" the "integralprobability of responses of the population" and the "relativelocal efficiency". This approach is eventually applied to va-rious biological end points illustrating its merits.

Staff member CEC, Bruxelles

EXCITATJDNS IN CONBEW&LD BIOLOGICALLATTER

Institute of Nuclear Research,250 68 fiez, CS£H

In living matter, electronic excitations nay ha-/u a collective character which is reviewed herein siuple physical terms. In liquids and orderedsolids the collective excitations appear as plas-nons or excitons. Flasnions are delocalized elect-ronic perturbations of a huge number of oscillat-ing electrons decaying very quickly into localizedelectronic perturbations, mainly low-energy ioniz-ations, Excitons are very light, moving quantumqua si-par t i d e s carrying energy, charge and infor-mation in structured biological systems. In defor-mable soft structures collective excitations appe-ar as solitons behaving as rather massive quasi-purt ides of combined quantum and classical char-acter. Solitons are relatively stable micro-objects,-.u.le to transfer energy, charge, mass, and biolo-gical information along such biological structuressi, (chains of) macromolecules, fibres, membranes;?.d surfaces. Whereas plasmons and excitons appear

•.~ less stable quasi-stationary solutions of 1 i -.'•. o a r field equations, solitons emerge as verystable singular solutions of n o n l i n e a rfield equations only, governing the highly organ-ized living matter. Some photobiological and radi-ation biological consequences of collective elect-ronic excitations are suggested*

Chromatin features as a factor of radiosensitivity

+G. Seibold*, E. Budzicka

*Strahlenzentrum UniversitSt Giessen, BRD

+Institute of Nuclear Research, Warsawa, Poland

Temporal processes occure in nuclear chromatinstructures in a single cell during the cell cycleor after treatments with different agents (i.e.irradiation or coffein). These processes can beanalysed by high resolution scanning photometrywhich yield, in a digitised nuclear image reflecting,the topographic distribution, the granularity andthe condensed-or non condensed chromatin by quanti-tative pattern analysis.

The application of this procedures to twomammalian cell lines (L 5178 Y-R and L 5178 Y-S)which are cross sensitive to UV- and X-rays showssignificant differences in the nuclear matrix be-fore and after irradiation. On the basis of thesesingle cell measurements, the cell populationcould be better characterised and classified anda correlation made between Chromatin pattern andradiosensitivity. Cells with more condensed chro-matin portions in the nuclei seems to be moresensitive against X-rays compared to those whichhave a more homogenous chromatin matrix.

DOSIMETRY OF RADON DAUGHTERS - RATIO OP VOLUME ACTI-VITIESBURIAN* I«, &rfD, A,Labour Medicine Institute of Uranium Industry^Pfibram, CSSR

Recent development of radon daughters dooimetryhas boon caused by soma other pathways loading toa significant irradiation of man* In addition to theclassical sources represented first of all by miningand milling radioactive ores the exposure to radondaughters in flats, schools, nurseries etc. has beeninvestigated. The source of radon lies either in un-derground or the radon is released from radium com-prised in building materials. For the evaluation ofexposure the methods of active and passive dosimotri-©s can be used. Two -basic approaches aro applicatodin active dosim^try systems the calculation of expo«euro by Markovs'method or by using individual dosi-meter,, In CSSR the intake of miners is tostod byMarkovs'mothod in gonoral and an individual dosimo-tox* is stop by stop introduced,, In this doeimetorthe detector KODAK LR 115 covorod by a foil reducingthe energy of alpha particles io uood and the numberof tracks is evaluated according to the equation

P * 0.42 . d/Q P.«.intake in 10 9 MoV «d...track density 104 cm" ,Q...volume velocity in l.h

*The intake of general population (in flats etc.) has :

been measured by a passive dosiraetry method. The de-tector KODAK LR 115 has b<?» n used. After 1 years ex-posure and a chemical working up to the number oftracks is to be evaluated according to the equationI « d.P I.,.time integral in 10%eV.h.l

d...track dernity lO^cm""^F...factor correcting the influence of

chemical working up and of tha eva-luating worker

DEPEITOEUCE OF THE RELATIVE BIOLOGICAL EFFICIENCYOK THE PAST NEUTRONS ENERGY.V,INDIK,V.BUKANOV,L.MBLNICHENKO,N.VLASOVAInstitute of Oncology Problems,Acad.Sci.of the Uk-rainian SSR,Kiev,USSR

The influence of the energy value of the neut-rons and the doze power on their biological effici-ency has been studied.Line mice Ccyblack and microorganisms Streptomyces robeus were irradiated by neut-rons of spectra fission with the doze power of 0,07-0,08 Gy/min and by the fast neutrons obtained fromthe dX50MeVj-*Be with the doze power of about 0,2Gy/min and also with the doze power of about 2Gy/min.

As a standard radiation gamma rays of the source60-Co were used.The analysis of the animals deathspermitted to determine the value of semi-lethal do-zes that account for neutrons of spectra fission2,51(2,29r2$72);for the fast neutrons from d£50MeVl*Be with the doze power of 0tGJy/min-4t78(4»12f5.44iand with the doze power of 2Gy/min~5,i6(4,66T5t°6)Gy-

Doze-effect dependence investigation on the cellmodel permitted to determine the RBE value of theinvestigated radiations from the ratio of the indicesDo7;the RBE value accouns for 4,3+0,2 for the reut-rons of spectra fission and for 175+0,1 for the fastneutrons from d.( 50MeV J-*Be. ""

Hence,the biological efficiency depends on thefast neutrons energy and for neutrons from d£50MeV/->Be does not depend on the doze power in the range of0,2-2Gy/min,

FINDINGS ON PIGLETS AFTER COMBINED APPLICATION OFHYPERTHERHIA AND RADIATIONDAUTERSTEDT. V.. T.HERRMANN, J. SCHORCHT

Medizinische Akademie, Radiologisehe Klinik, undForschungsinstitut Manfred von Ardenne, DDR-DreBden

Eight piglets of the raoe "Edelschwein" were sub-jected to a combined treatment with hyperthermiaand subsequent x-irradiatlon of the right lung. Thehyperthermia was induced by radiofrequeney with aninductive-applicator coil (Seleototherm ; 27,17 MHz;1,2-8 kW, 11 m wavelength). The aim of this measu-re was the generation of a temperature of 42 C overa period of 5 x 60 min; the temperature was taken byhigh-frequency-inert sensor, positioned in the retro-sternal space. The Irradiation was carried out witha telecobalttherapy treatment unit with isocentrictechnology ( 5 x 4 Gy). Roentgenographic folio- -upcontrol of the thorax organs and laboratory investi-gations of function al organ parameters in the bloodled to stateinentn concerning the temporal progressof radiogenic changes of the lungs and tolerance offractionated heating. After having killed the ani-mals histological examinations of correspondingregions of the right and left lung were carried out.The whole material was compared with the dates ofanimals which had been only irradiated with identicaldoses but had not been heated, The results can bedivided into acute changes of the lung as detectedby x-rays (roentgenographic changes) and into histo-logically traceable chronic changes. The hiBtolo-gical and histochemical changes of the lungs treatedin both ways demonstrate a thermal enhancement ratiofor the biological effect of ionizing radiation.

.1 r

About dose-time behavolr at brachy therapy0. Kob and A* KrieeterClinic and Policlinic of Radiology, Friedrich-Schiller-Univeralty, Dene, G.D.R,

The transielon from the conventional brechytherapy to the after--loading method aeke forrelationa of the biological -effectivity betweenthe two methoda. Analyzing the given Methods& fflodiflcatod ieoeffect relation onjbhe beeia ofthe NSD-concaption la proposed, which expressesthe biological effect on doee application* ofany period in relation to the short tineirradiation* Statooonte of effect relations,which are not limited by validity region*, arttcompared with other ieoeffect doum propoeale andexplained by examples,.

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