Biological Effects of Ionizing Radiation at Molecular And1

7/25/2019 Biological Effects of Ionizing Radiation at Molecular And1

1/36

BIOLOGICAL EFFECTS OF IONIZING

RADIATION AT MOLECULAR AND

CELLULAR LEVELS

BIOLOGICAL EFFECTS OF IONIZING

RADIATION AT MOLECULAR AND

CELLULAR LEVELS

Module VIII-a


2/36

Module MedicalVIII.

- 2

Historical backgro!"


3/36

Module MedicalVIII.

- 3

Wilhelm Conrad Roentgen

Disco#$r% o& ' ra%s

()*+,-


4/36

Module MedicalVIII.

- 4Antoine Henri Becquerel Marie Curie

Disco#$r% o& ra!i./s !atral

ra"ioacti#it%


5/36

Module MedicalVIII.

- 5

First radiation-induced skin cancerreported

in 1902 First radiation-induced leukemiadescribed

in 1911

First r$0orts o! 1ar.&l

$&&$cts o& ra"iatio!

)+23s4 bone cancer a.o!g

ra"i. "ial 0ai!t$rs

)+53s4 liver cancer and leukemia"$ to T1rotrast a".i!istratio!

)+63s4 $7c$ss leukemia a.o!g

&irst ra"iologists


6/36

Module MedicalVIII.

- 6

St"i$s o& 8a0a!$s$

A9bo.b sr#i#ors


7/36Module MedicalVIII.

- 7

E&&$cts o& ra"iatio! o! c$lls at

ato.ic l$#$l

Io!i:atio!E7citatio!



- 8

M$c1a!a!is.s o& "a.ag$

at .ol$clar l$#$l



- 9

Dir$ct actio!

Ionizing radiation + RH R-+ H+

OH IR C = NH

imidol (enol)

O IIR C = NH2

amide (ketol)

Tautomeric Shifts

Bond breaks



- 10

e-X ray

rayP+

OH

HOH-

H+

Ho

OHo

I!"ir$ct actio!


11/36

Module MedicalVIII.

- 11

Ra"iol%sis o& H2O

.ol$cl$

Shared electron

Shared electron

H-O-H H++ OH- ioni!ation"

H-O-H H#+OH# $ree radical%"


12/36

Module MedicalVIII.

- 12

R$actio!s ;it1 &r$$ ra"icals

H3< OH3 HOH (r$co.bi!atio!-

H3 < H3 H2

("i.$r-

OH3


13/36

Module MedicalVIII.

- 13

E&&$cts o& o7%g$! o! &r$$

ra"ical &or.atio!

O7%g$! ca! .o"i&% t1$ r$actio! b%

$!abli!g cr$atio! o& ot1$r &r$$ ra"ical

s0$ci$s ;it1 gr$at$r stabilit% a!" lo!g$r

li&$ti.$s

H3


14/36

Module MedicalVIII.

- 14

Li&$ti.$s o& &r$$ ra"icals

&nm

Becau%e %hort li$e o$ %im'le $ree radical% (#-(#%ec") only tho%e $ormed in *ater column o$ -&nm around ,A are a.le to 'artici'ate inindirect e$$ect

Ho

OHo Ho

OHo

HOo RO

o


15/36

Module MedicalVIII.

- 15

R$latio! b$t;$$! LET a!"

actio! t%0$

Dir$ct actio! is 0r$"o.i!a!t ;it1

1ig1 LET ra"iatio!= $>g> al01a

0articl$s a!" !$tro!s

I!"ir$ct actio! is 0r$"o.i!a!t ;it1

lo; LET ra"iatio!= $>g> ' a!"

ga..a ra%s


16/36

Module MedicalVIII.

- 16

Bioc1$.ical r$actio!s

;it1 io!i:i!g ra"iatio!

DNAis 0ri.ar% targ$t&or c$ll "a.ag$ &ro. io!i:i!g ra"iatio!


17/36

Module MedicalVIII.

- 17

T%0$s o& ra"iatio! i!"c$"

l$sio!s i! DNA

Single-%trand .rea/% ,ou.le %trand .rea/%

Ba%e damage


18/36

Module MedicalVIII.

- 18

M$c1a!is.s o& DNA

r$0air


19/36

Module MedicalVIII.

- 19

DNA r$storatio! &ailr$

0nre1oined ,Adou.le %trand .rea/%

Incorrect re'air o$

,A damage

Cytoto2ic e$$ect Mutation%


20/36

Module MedicalVIII.

- 20

C1ro.oso.$s


21/36

Module MedicalVIII.

- 21

DNA l$sio!s a!"

c1ro.oso.$ ab$rratio!s

,A S3456

S7RA, BR6A8

,A ,O0B56

S7RA, BR6A8


22/36

Module MedicalVIII.

- 22

Ra"iatio! i!"c$"

c1ro.oso.al ab$rratio!s


23/36

Module MedicalVIII.

- 23

E&&$ct o& ra"iatio! o! c$ll

C$ll ki!$tics


24/36

Module MedicalVIII.

- 24

Ra"ios$!siti#it% o& c$ll

i! c$ll c%cl$

Relative

Survivability

4( S 4 4(MRelative survivability o !ells irradiated in dierent "#ases o t#e

!ell !y!le$ Syn!#ronised !ells in late %2and in mitosis (&) s#o'ed

reatest sensitivity to !ell killin$


25/36

Module MedicalVIII.

- 25ORMA5 IRRA,IA76,

Mitotic "$at1

B$rgo!i@ a!" Tribo!"$as/


26/36

Module MedicalVIII.

- 26

The most radiosensitive cells are

acti#$l% 0roli&$rati!g?"i#i"i!g at t1$ti.$ o& $70osr$

!"i&&$r$!tiat$" (!o!9s0$ciali:$" i!

strctr$ a!" &!ctio!-

B$rgo!i@ a!" Tribo!"$as/

la;/ ()+3-


27/36

Module MedicalVIII.

- 27

I!t$r01as$ "$at1

1% ar$ 0$ri01$ral bloo" l%.01oc%t$s 1ig1l%

s$!siti#$ to ra"iatio!= alt1og1 ;$ll "i&&$r$!tiat$"


28/36

Module MedicalVIII.

- 28

Ra"iatio! i!"c$"

.$.bra!$ "a.ag$


29/36

Module MedicalVIII.

- 29

Dose rate and fractionation

Radiation quality

Temperature

Chemical modificationOxygen

Radiosensitizing agentsRadioprotectie agents

Mo"i&icatio! o& ra"iatio!

i!r%


30/36

Module MedicalVIII.

- 30

Dos$ rat$ a!"

&ractio!atio!

3

3>,

)

)>,

2

2>,

5

3

3>,

)

)>,

2

2>,

5

9rolonged e2'o%ure*ith lo*er do%e rate

Acutee2'o%ure*ith highdo%e rate

:ractionateddo%e

Acutedo%e

Ti.$Ti.$


31/36

Module MedicalVIII.

- 31

Ra"iatio! alit%

Survival curve for mammalian cells


32/36

Module MedicalVIII.

- 32

Survival curve for mammalian cells

exposed to

high- (A) and low-!T (") radiation

A

B

Dq

n

D0 D0

1-1/e1-1/e,037


33/36

Module MedicalVIII.

- 33

T$.0$ratr$

For c$ll kili!g $&&$cts= tiss$s ar$

.or$ ra"ios$!siti#$ at 1ig1$r

t$.0$ratr$s

C1ro.oso.$ ab$rratio!s i!cr$as$

at lo;$r t$.0$ratr$s (s00r$ssio!

o& r$0air 0roc$ss-


34/36

Module MedicalVIII.

- 34

C1$.ical .o"i&icatio!4

o7%g$!

OER Dos$ r$ir$" to cas$ $&&$ct ;it1 o7%g$!

Dos$ r$ir$" to cas$ $&&$ct ;it1ot o7%g$!

Dissol#$" o7%g$! i! tiss$s i!cr$as$s

stabilit% a!" to7icit% o& &r$$ ra"icals

O7%g$! $!1a!c$.$!t ratio (OER- is"$t$r.i!$" b%4

T1$ OER 1as a .a7i.. #al$ o& 5>3


35/36

Module MedicalVIII.

- 35

Ra"ios$!siti:i!g ag$!ts

Halog$!at$" a!" sbstitt$"

a!alog$s o& DNA bas$s4 ,9bro.o9

racil a!" 9t1io9ga!i!$

El$ctroa&&i!ic co.0o!"s4

Nitroi.i"a:ol$s (.iso!i"a:ol$=

!itroi.i"a:ol$= a!" !itro&ra!-s$!siti:atio! $!1a!c$.$!t ratio

(SER-o& )>2 to )>6


36/36

Ra"io0rot$cti#$

ag$!tsT1iols(csteine! 2-"ercaptoet#la"ine!csta"ine and t#iourea$. %#iols #a&e dosereduction 'actor ()*F$ ratio o' 1.4 to 2.0

%#e are t#ou+#t to protect cells bsca#$!gi!g &r$$ ra"icals0ro"ci!g 1%0o7ia

t$.0oraril% i!1ibiti!g DNA s%!t1$sis= allo;i!gti.$ &or t1$ r$0air $!:%.$s to co.0l$t$ r$0airo& sbl$t1al "a.ag$

&or.i!g "isl01i"$ bo!"s i! 0rot$i!s= t1$r$b%

t t1 i t1

Documents

Biological Effects of Ionizing Radiation at Molecular And1