GENOTOXIC EFFECTS OF ALPHA-HEXACHLOROCYCLOHEXANE IN PRIMARY CULTURES OF RODENT AND HUMAN HEPATOCYTES

The genotoxicity of alpha-hexachlorocyclohexane (alpha-HCH) was evalua ted in primary cultures of mouse, rat and human hepatocytes. DNA fragm entation was measured by the alkaline elution technique and DNA repair synthesis by quantitative autoradiography, A 20 h exposure to subtoxi c concentrations ranging from 0.056 to 0.32 mM produced a dose-depende nt frequency of DNA breaks in rat hepatocytes and in hepatocytes from four of five human donors, but not in mouse hepatocytes. DNA repair in duction was absent in hepatocytes from all three species, The reductio n in the frequency of DNA breaks observed in rat hepatocytes simultane ously exposed to metyrapone suggests that alpha-HCH is transformed int o reactive species by a cytochrome P450-dependent reaction. The detect ion of DNA fragmentation but not of DNA repair synthesis may be tentat ively explained by assuming that a-HCH behaves as a chemical eliciting short patch DNA repair, which is more easily revealed as genotoxic by the occurrence of DNA single-strand breaks.