USE OF METABOLICALLY COMPETENT HUMAN HEPATOMA-CELLS FOR THE DETECTIONOF MUTAGENS AND ANTIMUTAGENS

The human hepatoma line (Hep G2) has retained the activities of variou s phase I and phase II enzymes which play a crucial role in the activa tion/detoxification of genotoxic procarcinogens and reflect the metabo lism of such compounds in vivo better than experimental models with me tabolically incompetent cells and exogenous activation mixtures. In th e last years, methodologies have been developed which enable the detec tion of genotoxic effects in Hep G2 cells. Appropriate endpoints are t he induction of 6-TG(r) mutants, of micronuclei and of comets (single cell gel electrophoresis assay). It has been demonstrated that various classes of environmental carcinogens such as nitrosamines, aflatoxins , aromatic and heterocyclic amines and polycyclic aromatic hydrocarbon s can be detected in genotoxicity assays with Hep G2 cells. Furthermor e, it has been shown that these assays can distinguish between structu rally related carcinogens and non-carcinogens, and positive results ha ve been obtained with rodent carcinogens (such as safrole and hexameth ylphosphoramide) which give false negative results in conventional in vitro assays with rat liver homogenates. Hep G2 cells have also been u sed in antimutagenicity studies and can identify mechanisms not detect ed in conventional in vitro systems such as induction of detoxifying e nzymes, inactivation of endogenously formed DNA-reactive metabolites a nd intracellular inhibition of activating enzymes, (C) 1998 Elsevier S cience B.V. All rights reserved.