DNA-DNA cross-links contribute to the mutagenic potential of the mycotoxin patulin

Abstract

The mycotoxin patulin (PAT), which occurs in various foods, induces mutations in cultured mammalian cells. However, the mechanism underlying the mutagenic potential of PAT is far from clear. In order to further clarify the mutagenic mode of action of PAT, we investigated the potential of PAT to induce DNA strand breaks, oxidative DNA modifications, and DNA-DNA cross-links using an alkaline filter elution technique and a fluorescence-based assay. In concentrations known to induce mutations in V79 cells (0.5-2.5 microM), PAT also induced DNA-DNA cross-links. In contrast, no effect on the number of DNA strand breaks (i.e., DNA single and double strand breaks as well as alkali-labile sites) or fpg-sensitive sites (i.e., oxidative DNA modifications) was observed in the non-cytotoxic concentration range. Thus, the present study demonstrates for the first time the direct reactivity of PAT towards DNA in a cellular system, which might have implications for the toxicological evaluation of this widespread mycotoxin.