Use of metabolically competent human hepatoma cells for the detection of mutagens and antimutagens

Siegfried Knasmüller, Wolfram Parzefall, Ratna Sanyal, Sonja Ecker, Christina Schwab, Maria Uhl, Volker Mersch-Sundermann, Gary Williamson, Gerhard Hietsch, Theo Langer, Firouz Darroudi, Adayapalam T. Natarajan

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328 Citations (Scopus)

Abstract

The human hepatoma 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 reflect the metabolism of such compounds in vivo better than experimental models with metabolically incompetent cells and exogenous activation mixtures. In the last years, methodologies have been developed which enable the detection of genotoxic effects in Hep G2 cells. Appropriate endpoints are the 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 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 safrole and hexamethylphosphoramide) which give false negative results in conventional in vitro assays with rat liver homogenates. Hep G2 cells have also been used in antimutagenecity 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.

Original languageEnglish
Pages (from-to)185-202
Number of pages18
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Volume402
Issue number1-2
DOIs
Publication statusPublished - 18 Jun 1998
Externally publishedYes

Keywords

  • Antimutagen
  • Human Hep G2 cell
  • Metabolic activation
  • Mutagenecity

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