Induction of sister-chromatid exchanges, micronuclei and gene mutations by indirectly acting promutagens using human hepatoma cells as an activation system

By Darroudi, F. - Natarajan, A.T.

An established human hepatoma cell strain (designated Hep G2) was used in sister-chromatid exchange (SCE) and micronuclei (MN) assays to study, in vitro, the genotoxic potentials of indirectly acting promutagenic carcinogens, such as 2-acetylaminofluorene (2-AAF) and hexamethylphosphoramide (HMPA), and a non-carcinogen, 4-acetylaminofluorene (4-AAF). In addition, Hep G2 S9-fractions were isolated and used to activate the same chemicals using Chinese hamster ovary (CHO) cells as target cells in vitro. The percentage survival and the frequencies of MN, SCEs and point mutations (at the HPRT locus) were used as biological endpoints. A dose-dependent increase in the frequencies of SCEs, MN, cytotoxicity, and/or point mutations was found in Hep G2 cells, and in CHO cells in the presence of Hep G2 S9-fractions, with 2-AAF and HMPA, but with 4-AAF no increase was found. The results obtained demonstrate that the Hep G2 cells and their S9-fractions are capable of activating different classes of mutagens to form biologically active metabolites.