Sensitivity to genotoxic effects of bleomycin in humans: possible relationship to environmental carcinogenesis.
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.
Hsu
T C
TC
Department of Cell Biology, University of Texas M. D. Anderson Cancer Center, Houston 77030.
Johnston
D A
DA
Cherry
L M
LM
Ramkissoon
D
D
Schantz
S P
SP
Jessup
J M
JM
Winn
R J
RJ
Shirley
L
L
Furlong
C
C
D000328:Adult; D000368:Aged; D001761:Bleomycin / Q000633:toxicity; D002869:Chromosome Aberrations; D004198:Disease Susceptibility; D004785:Environmental Pollutants / Q000009:adverse effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009152:Mutagenicity Tests; D009153:Mutagens / Q000009:adverse effects*; D009369:Neoplasms / Q000139:chemically induced / Q000209:etiology* / Q000235:genetics; D012907:Smoking / Q000009:adverse effects / Q000235:genetics
D004785:Environmental Pollutants; D009153:Mutagens; D001761:Bleomycin