Interindividual variation of carcinogen activation by human liver homogenates. A study using dimethylnitrosamine (DMN) and cyclophosphamide (CP) as precursor genotoxic agents and clastogenicity and induction of sister chromatid exchanges in Chinese hamster V79-E cells as endpoints.
9000 g supernatants of liver homogenates from 6 kidney transplant donors were checked in combination with Chinese hamster V79-E cells in vitro for their capacity to activate DMN and CP. 9000 g fractions were standardized on protein content. Induction of chromatid aberrations (clastogenicity assay) and sister chromatid exchanges (SCE assay) served as parameters. DMN activation showed a 1.3-fold inter individual variation and was in the same order of magnitude as that observed with rat liver 9000 g fractions. Striking interindividual differences were found when CP was applied as reference precarcinogen. Most of the samples had a distinctly lower activity than that of the rat but reached, in one case, a similar level. Methodological problems and limitations of genotoxicity tests for precarcinogen screening with respect to extrapolation of results to man are discussed.
D000818:Animals; D002869:Chromosome Aberrations; D006224:Cricetinae; D003434:Crossing Over, Genetic / Q000187:drug effects*; D046508:Culture Techniques; D003520:Cyclophosphamide / Q000378:metabolism / Q000633:toxicity*; D004128:Dimethylnitrosamine / Q000378:metabolism / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008938:Mitosis / Q000187:drug effects; D009115:Muridae; D009154:Mutation; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000235:genetics; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D014020:Tissue Extracts / Q000494:pharmacology*
D014020:Tissue Extracts; D003520:Cyclophosphamide; D004128:Dimethylnitrosamine