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

Abstract

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.