Induction of micronuclei, DNA strand breaks and HPRT mutations in cultured Chinese hamster V79 cells by the phytoestrogen coumoestrol

Coumoestrol (COUM), genistein (GEN) and daidzein (DAI) are major phytoestrogens present in numerous plants eaten by humans and food-producing animals. Little is known about the genotoxicity of these natural compounds. The effects of COUM, GEN and DAI were studied in cultured Chinese hamster V79 cells at various endpoints. None of the substances affected the cytoplasmic microtubule complex or the mitotic spindle. However, COUM and GEN but not DAI proved to be strong inducers of DNA strand breaks and micronuclei containing acentric fragments, as shown with antikinetochore antibodies. The clastogenicity of GEN may be due to its non-intercalative inhibitory effect on topoisomerase II, whereas COUM may act through topoisomerase II inhibition and/or DNA intercalation. COUM was also a clear inducer of hypoxanthine guanine phosphoribosyltransferase (HPRT) mutations in V79 cells; GEN was only marginally active and DAI inactive at this endpoint. This is the first report on the clastogenicity and mutagenicity of COUM in mammalian cells.