In vitro and in vivo induction of chromosome aberrations by alpha- and beta-zearalenols: comparison with zearalenone

Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by Fusarium fungi. It contaminates different components of the food chain and can cause serious economic and public health problems. The major metabolites of ZEN in various animal species are alpha- and beta-zearalenol (α-, β-ZOL). Some in vivo studies have shown that these two metabolites are as toxic as the mother molecule (ZEN), but other investigations have demonstrated that α- and β-ZOL are less toxic than ZEN. Thus, the aim of the present study was to evaluate cytotoxicity and genotoxicity of α- and β-ZOL in vivo, in mouse bone-marrow cells and in vitro, in cultured HeLa cells, and to compare it with ZEN. ZEN showed the same cytotoxicity as α-ZOL and both are more cytotoxic than β-ZOL. Genotoxicity of ZEN and its derivatives was assessed by the chromosome aberration assay. Our results show that ZEN as well as α- and β-ZOL increased the percentage of chromosome aberrations in mouse bone-marrow cells and in HeLa cells. In the two systems, ZEN and α-ZOL exhibited the same range of genotoxicity and both were more genotoxic than β-ZOL. Furthermore, our results show that either ZEN or its two metabolites inhibited cell viability in a dose-dependent manner. We conclude that biotransformation of ZEN may be considered as only a partial detoxification pathway since the resulting metabolites remain relatively toxic.