Interindividual variation in the responses of cultured human lymphocytes to exposure from DNA damaging chemical agents: interindividual variation to carcinogen exposure.
Human population variability to standardized doses of N-acetoxy-2-acetylaminofluorene (NA-AAF) and 7, 12-dimethylbenz(a) anthracene (DMBA) was determined in cultured lymphocytes by measuring (a) differential stimulation of unscheduled DNA synthesis after 1 h induction of DNA damage by 10 micrometer NA-AAF, (b) the level of NA-AAF induced chromosome aberrations remaining after 8 h of DNA-repair synthesis, and (c) the level of [3H]DMBA bound to DNA after 18 h incubation of resting lymphocytes in 5 micrometer DMBA. All 3 parameters indicated individual variation to carcinogen exposure and were correlated to the population differences in age, sex, blood pressure and mortality rates. Males always had a greater potential to accumulate DNA-damage than did females regardless of the sampled population. DNA-damage potentials increased with increasing age, blood pressure or mortality rates. There was always proportionally greater DNA-damage potentials in the males than in females. The in vitro response of mature granulocytes to a 10 micrometer NA-AAF dose, as estimated by [3H] thymidine incorporation from unscheduled DNA synthesis, was much lower than lymphocyte response. Nevertheless, individual variations in granulocyte NA-AAF induced unscheduled DNA synthesis paralleled the inter-individual fluctuations observed in the lymphocyte responses to NA-AAF.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology; D000099:Acetoxyacetylaminofluorene / Q000494:pharmacology; D000367:Age Factors; D001794:Blood Pressure; D002273:Carcinogens / Q000494:pharmacology*; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D004260:DNA Repair; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D012737:Sex Factors
D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene; D000099:Acetoxyacetylaminofluorene; D004247:DNA