Toxicities induced in cultured cells exposed to zearalenone: apoptosis or mutagenesis?

Zearalenone (ZEN) is a fusarotoxin produced mainly by Fusarium graminearum in temperate and warm countries. ZEN has several adverse effects on humans and animals. It has a strong estrogenic activity associated with hyperestrogenism and leads to several physiological alterations in the reproductive tract. Even though the mutagenic and genotoxic proprieties of ZEN have been described recently, its molecular mechanisms of action are not completely understood. The aim of this study was to determine the involvement of other possible mechanisms in ZEN-induced toxicities. Each of the following toxicities, cytotoxicity, cell cycle perturbation, genotoxicity, and mutagenicity, was monitored in Vero cells exposed to ZEN. Our results showed that ZEN-reduced cell viability correlated to cell cycle perturbation-induced DNA fragmentation, resulting in DNA-laddering patterns on agar gel electrophoresis. This observation is consistent with apoptosis, which was confirmed by induction of apoptotic bodies. Moreover, ZEN induced in a concentration-dependant manner the formation of micronuclei and chromosome aberrations. This apparent contradiction between the apoptotic and mutagenic effects of ZEN can be explained by the modification of normal cellular regulation inducing apoptotic or antiapoptotic factors resulting from a lack of or an incorrect DNA-reparation in relation to cell exposure to the toxin.