INDUCTION OF MICRONUCLEI IN METABOLICALLY COMPETENT RAT HEPATOMA-CELLLINES BY THE PROMUTAGENS 7,12-DIMETHYLBENZ[A]ANTHRACENE, BENZO[A]PYRENE AND CYCLOPHOSPHAMIDE

The capability of two rat hepatoma cell lines, H4IIEC3/G(-) and 2sFou, to detect genotoxicity of xenobiotics, was evaluated in a micronucleu s assay. In this system, the cells act as the activation source as wel l as the target cells for the DNA damage. The study was performed usin g 7,12,-dimethylbenz[a]anthracene, benzo[a]pyrene and cyclophosphamide , as pro-mutagens and mitomycin C as a direct acting mutagen, In both cell lines a significant micronucleus induction was observed after exp osure to each test compound, starting from 25 nM for 7,12-dimethylbenz [a] anthracene, 8 mu M for benzo[a]pyrene, 0.5 mM for cyclophosphamide and 0.4 mu M for mitomycin C. A period of 24 h treatment and 48 h gro wth was sufficient for induction and expression of micronuclei, The tw o hepatoma lines behave in a similar way with regard to the pro-mutage n activation. The results obtained in this study with these differenti ated hepatoma lines demonstrate that they are metabolically competent to activate the promutagens 7,12-dimethylbenz[a]anthracene, benzo[a]py rene and cyclophosphamide into their biologically active metabolites a s measured by micronucleus induction in our experiments. However, the variable dose responses to 7,12-dimethylbenz[a]anthracene and benzo[a] pyrene in some of the repeated experiments, suggest unstable activity of enzymes involved in polycyclic aromatic hydrocarbons metabolism in these cell lines.