Use Of Metabolically Competent Human Hepatoma Cells of The Detection Of Mutagens And Antimutagens.

ABSTRACT

The human hepatoma cell line (Hep G2) has retained the activities of various phase I and phase II enzymes which play a crucial role in the activation/detoxification of genotoxic procarcinogens and reflects the metabolism of such compounds in vivo better than experimental models with metabolically incompetent cells and exogenous activation mixtures. In recent years, methodologies have been developed which enable the detection of genotoxic effects in Hep G2 cells. Appropriate endpoints are the induction of 6-TGr mutants, of micronuclei and of comets (single cell electrophoresis assays). It has been demonstrated that various classes of environmental carcinogens, such as nitrosamines, aflatoxins, aromatic and heterocyclic amines and polycyclic aromatic hydrocarbons can be detected in genotoxicity assays with Hep G2 cells. Furthermore, it has been shown that these assays can distinguish between structurally related carcinogens and non-carcinogens, and positive results have been obtained with rodent carcinogens (such as safrol and hexamethylphosphoramide) which give false negative results in conventional in vitro assays with rat liver homogenates. Hep G2 cells have also been used in antimutagenicity studies and can identify mechanisms not detected in conventional in vitro systems such as induction of detoxifying enzymes, inactivation of endogenously formed DNA- reactive metabolites and intracellular inhibition of activating enzymes.