Genistein and delphinidin antagonize the genotoxic effects of the mycotoxin alternariol in human colon carcinoma cells

Scope Although associated with anti‐oxidative properties, genistein has been reported to induce DNA strand breaks, whereby oxidative stress and topoisomerase poisoning are considered as potential mechanisms. In contrast, delphinidin, a catalytic topoisomerase inhibitor, is known to suppress the DNA‐damaging properties of several topoisomerase poisons. Recently, alternariol, a mycotoxin produced by Alternaria spp., was found not only to induce oxidative stress but also to act as a topoisomerase poison. As both, polyphenols and mycotoxins, might occur in our nutrition simultaneously, the question was addressed whether potential combinatory effects on DNA integrity have to be considered. Methods and results We determined combinatory effects of either genistein or delphinidin with alternariol in HT‐29 cells. Cytotoxicity was assessed by WST‐1 and SRB assays, whereby only weak interactions were observed. The comet assay revealed significant antagonistic interactions of both polyphenols with the genotoxicity of AOH. The underlying mechanism comprises the suppression of alternariol‐mediated stabilization of DNA/topoisomerase‐II‐intermediates, as observed in the ICE assay. Furthermore, DEL but not GEN was found to suppress AOH‐mediated oxidative stress. Conclusion Our data indicate that a respective polyphenol‐rich diet might aid to protect against genotoxic damages caused by AOH, whereby bioactive concentrations of DEL are predominantly expected locally in the intestines. In this study, the potential contribution of the dietary polyphenols delphinidin (DEL) and genistein (GEN) were examined against the genotoxic effects of the Alternaria mycotoxin alternariol (AOH) on human colon cells. Both DEL and GEN were found to impair the topoisomerase II poisoning properties of AOH in the ICE assay, but only DEL also to reduced oxidative stress caused by AOH. These results were supported by a significant antagonistic interaction of both polyphenols with AOH's genotoxicity as observed in the comet assay.