1
18 The interaction of exposure with age at ob- servation fits a relative risk model well. The similarity of these results to a recent study of Swedish iron miners with similar levels of relatively low exposure suggests that exposure to radon daughter products may be a major contributory factor to lung can- cer occurring among nonsmokers in the general population. The results also rein- force concerns as to the appropriateness of present occupational exposure standards. Silicosis and Bronchial Carcinoma: Anatomic Pathology and Problems in Expertising. Reitemeyer, E., Bohm, E., Muller, K.-M. In- stitut fur Pathologie der Berufsgenos- senschaftlichen Krankenanstalten 'Ber~insheil' - Universitatsklinik, D-4630 Bochum, Germany. Prax. Klin. Pneumol. 39: 679-680, 1985. Evaluation of 7,122 postmortem findings in miners with silicosis, obtained during 1964 to 1983, yielded 966 times a combina- tion of silicosis with bronchial carcinoma (= 13.6%). According to established criteria, a silicotic carcinoma in scar tissue was diagnosed 45 times (4.7% of all bronchial carcinomas). Statistical com- parisons alone (age, degree of silicosis, topography and histological tumour type) with the silicosis-independent bronchial carcinoma did not supply any pointers for diagnosing a silicotic carcinoma in scar tissue. There are also no statistically manifest differences in respect of aetiology and pathogenesis, with the exception of a cocarcinogenic factor due to the silicotic scar. Hence, detailed individual morphologi- cal examination with due consideration being given to the clinical findings, will always be necessary in each case for writing a sickness insurance expertise on a probable connection between silicosis and a bronchial carcinoma. 3. BASIC BIOLOGY. Induction of Squamous Cell Carcinoma in the Rat Lung by 1,6-dinitropyrene. Maeda, T., Tzumi, K., Otsuka, H. et al. Department of Pathology, School of Medicine, The University of Tokushima, Tokushima 770, Japan. J. Natl. Cancer Inst. 76: 693-701, 1986. The carcinogenicity of l-nitropyrene (I-NP) CAS: 5522-43-0) and 1,6-dinitropyrene ((I,6-DNP) CAS: 42397-64-8) was examined by their direct injection in a beeswax- tricaprylin vehicle into the lung of male F3~/DuCrj rats. Of 28 rats given 0.15 mg of 1,6-DNP, 21 (75%) developed squamous cell carcinomas, 2 (7%) developed undifferen- tiated carcinomas, and 2 (7%) had squamous metaplasias in the lung by 72 weeks. In 32 rats that received 1.5 mg of I-NP, neither carcinoma nor squamous metaplasia was in- duced. In all 19 rats (100%) given 0.5 mg of 3-methylcholanthrene (MCA) CAS: 56-49-5), squamous cell carcinomas were induced ear- lier than in rats treated with 1,6-DNP. In 1 of 31 rats (3%) given the beeswax- tricaprylin vehicle only, squamous metaplasia was induced. Distant metastases of induced tumors were observed in 4 rats treated with 1,6-DNP and in 1 rat receiving MCA. Two lung tumors induced by 1,6-DNP were successively transplanted into the same strain of rats for 3 generations. Metabolism of Benzo(a)pyrene in Monolayer Cultures of Human Bronchial Epithelial Cells from a Series of Donors. Siegfried, J.M., Rudo, K., Bryant, B.J. et al. Carcinogenesis and Metabolism Branch, United States Environmental Protection Agency, Research Triangle Park, NC 27711, U.S.A. Cancer Res. 46: 4368-4371, 1986. Benzo(a)pyrene (B(a)P) metabolism was measure in monolayer cultures of human bron- chial epithelial cells derived from 18 specimens of explanted tissue. Bronchial epithelial cells converted B(a)P to dihydrodiols, phenols, quinone derivatives, and polyhydroxylated forms. Sulfate and glufuronide conjugates of B(a)P metabolites were also detected. Both total metabolism and distribution of metabolites showed a 10- fold or greater variation in cultures from different specimens. When the data were divided according to smoking status, however, no differences in total metabolism, extent of conjugation, or distribution of metabolites could be demonstrated between the two groups. Wide variation (over lO00- fold) in the cytotoxicity of B(a)P towards cells derived from different specimens was demonstrated but could not be directly correlated to the extent of metabolic ac- tivation. The results suggest that human bronchial epithelial cells which are newly grown from explanted tissue of smokers in culture do not demonstrate enzymatic induc- tion. Variation among individuals observed in these studies probably represents basal differences in metabolic capability.

Metabolism of benzo(a)pyrene in monolayer cultures of human bronchial epithelial cells from a series of donors

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Page 1: Metabolism of benzo(a)pyrene in monolayer cultures of human bronchial epithelial cells from a series of donors

18

The interaction of exposure with age at ob-

servation fits a relative risk model well.

The similarity of these results to a recent

study of Swedish iron miners with similar

levels of relatively low exposure suggests

that exposure to radon daughter products may

be a major contributory factor to lung can-

cer occurring among nonsmokers in the

general population. The results also rein-

force concerns as to the appropriateness of

present occupational exposure standards.

Silicosis and Bronchial Carcinoma: Anatomic

Pathology and Problems in Expertising.

Reitemeyer, E., Bohm, E., Muller, K.-M. In-

stitut fur Pathologie der Berufsgenos-

senschaftlichen Krankenanstalten

'Ber~insheil' - Universitatsklinik, D-4630

Bochum, Germany. Prax. Klin. Pneumol. 39:

679-680, 1985.

Evaluation of 7,122 postmortem findings

in miners with silicosis, obtained during

1964 to 1983, yielded 966 times a combina-

tion of silicosis with bronchial carcinoma

(= 13.6%). According to established

criteria, a silicotic carcinoma in scar

tissue was diagnosed 45 times (4.7% of all

bronchial carcinomas). Statistical com-

parisons alone (age, degree of silicosis,

topography and histological tumour type)

with the silicosis-independent bronchial

carcinoma did not supply any pointers for

diagnosing a silicotic carcinoma in scar

tissue. There are also no statistically

manifest differences in respect of aetiology

and pathogenesis, with the exception of a

cocarcinogenic factor due to the silicotic

scar. Hence, detailed individual morphologi-

cal examination with due consideration being

given to the clinical findings, will always

be necessary in each case for writing a

sickness insurance expertise on a probable

connection between silicosis and a bronchial

carcinoma.

3. BASIC BIOLOGY.

Induction of Squamous Cell Carcinoma in the

Rat Lung by 1,6-dinitropyrene.

Maeda, T., Tzumi, K., Otsuka, H. et al.

Department of Pathology, School of Medicine,

The University of Tokushima, Tokushima 770,

Japan. J. Natl. Cancer Inst. 76: 693-701,

1986.

The carcinogenicity of l-nitropyrene

(I-NP) CAS: 5522-43-0) and 1,6-dinitropyrene

((I,6-DNP) CAS: 42397-64-8) was examined by

their direct injection in a beeswax-

tricaprylin vehicle into the lung of male

F3~/DuCrj rats. Of 28 rats given 0.15 mg of

1,6-DNP, 21 (75%) developed squamous cell

carcinomas, 2 (7%) developed undifferen-

tiated carcinomas, and 2 (7%) had squamous

metaplasias in the lung by 72 weeks. In 32

rats that received 1.5 mg of I-NP, neither

carcinoma nor squamous metaplasia was in-

duced. In all 19 rats (100%) given 0.5 mg of

3-methylcholanthrene (MCA) CAS: 56-49-5),

squamous cell carcinomas were induced ear-

lier than in rats treated with 1,6-DNP. In 1

of 31 rats (3%) given the beeswax-

tricaprylin vehicle only, squamous

metaplasia was induced. Distant metastases

of induced tumors were observed in 4 rats

treated with 1,6-DNP and in 1 rat receiving

MCA. Two lung tumors induced by 1,6-DNP were

successively transplanted into the same

strain of rats for 3 generations.

Metabolism of Benzo(a)pyrene in Monolayer

Cultures of Human Bronchial Epithelial Cells

from a Series of Donors.

Siegfried, J.M., Rudo, K., Bryant, B.J. et

al. Carcinogenesis and Metabolism Branch,

United States Environmental Protection

Agency, Research Triangle Park, NC 27711,

U.S.A. Cancer Res. 46: 4368-4371, 1986.

Benzo(a)pyrene (B(a)P) metabolism was

measure in monolayer cultures of human bron-

chial epithelial cells derived from 18

specimens of explanted tissue. Bronchial

epithelial cells converted B(a)P to

dihydrodiols, phenols, quinone derivatives,

and polyhydroxylated forms. Sulfate and

glufuronide conjugates of B(a)P metabolites

were also detected. Both total metabolism

and distribution of metabolites showed a 10-

fold or greater variation in cultures from

different specimens. When the data were

divided according to smoking status,

however, no differences in total metabolism,

extent of conjugation, or distribution of

metabolites could be demonstrated between

the two groups. Wide variation (over lO00- fold) in the cytotoxicity of B(a)P towards

cells derived from different specimens was

demonstrated but could not be directly

correlated to the extent of metabolic ac-

tivation. The results suggest that human

bronchial epithelial cells which are newly

grown from explanted tissue of smokers in

culture do not demonstrate enzymatic induc-

tion. Variation among individuals observed

in these studies probably represents basal

differences in metabolic capability.