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Sensitivity to genotoxic effects of bleomycin in humans: possible relationship to environmental carcinogenesis.

Abstract：

:Responses to the genotoxic effect of bleomycin in lymphocytes of blood cultures, expressed as the average number of chromatid breaks per cell (b/c), varied from less than 0.20 to more than 2.00 in 335 normal individuals. More than 11% of the subjects tested showed a b/c rate above 1.00 and more than 22% showed a b/c rate above 0.80. These individuals are considered sensitive to this radiomimetic drug. The distributional profile of bleomycin responses of the control individuals appears to be representative of the normal human population. In patients with cancers of the colon (83), upper aerodigestive tract (head/neck) (77), and lung (71), the frequencies of subjects in the hypersensitive class were found to be between 40 and 50%, and the response profiles were distinctly different from those of the control population. On the other hand, in a group of elderly cigarette smokers, who exhibited no symptoms of lung cancer, the bleomycin sensitivity profile was significantly skewed toward the more resistant stratum, with only one hypersensitive case among 56 individuals tested (1.78%). The sensitivity profile of patients with breast cancer (82) was similar to that of the control population. Our data suggest that: (1) mutagen sensitivity may play an important role in carcinogenesis of organs and tissues that have direct contact with the external environment (respiratory, digestive, and integumentary systems); (2) it appears to have no significant influence on carcinogenesis of tissues that are not directly exposed to the environment (e.g., breast, brain); and (3) it also has little impact on carcinogenesis in individuals with a hereditary predisposition to cancer (e.g., retinoblastoma, Gardner's syndrome). Development of more effective and precise test systems for carcinogen sensitivity is highly desirable for identification of persons at risk.

journal_name

Int J Cancer

journal_title

International journal of cancer

authors

Hsu TC,Johnston DA,Cherry LM,Ramkissoon D,Schantz SP,Jessup JM,Winn RJ,Shirley L,Furlong C

doi

10.1002/ijc.2910430310

subject

Has Abstract

pub_date

1989-03-15 00:00:00

pages

403-9

issue

eissn

0020-7136

issn

1097-0215

journal_volume

pub_type

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Sensitivity to genotoxic effects of bleomycin in humans: possible relationship to environmental carcinogenesis.