Genotoxic activity of four metabolites of the soy isoflavone daidzein.

Products containing phytoestrogens are increasingly promoted as the "natural" alternative to estrogen replacement therapy. In the present study, we have used the in vitro micronucleus assay in L5178Y mouse lymphoma cells to investigate the genotoxic potential of the isoflavone daidzein, and of four daidzein metabolites known to be formed in humans. Whereas no induction of micronuclei was observed with daidzein up to the limit of solubility (100 microM), all four daidzein metabolites, i.e. equol (2.3-fold induction at 100 microM), O-desmethylangolensin (6.2-fold induction at 10 microM), 4',6,7-isoflavone (6.7-fold induction at 100 microM) and 3',4',7-isoflavone (8.2-fold induction at 100 microM) induced micronuclei in a concentration-dependent manner. Thus, both reductive and oxidative metabolites of the soy isoflavone daidzein exhibit genotoxic potential in vitro.