Detection of epigenetic effects of citrinin using a yeast-based bioassay.

The present study investigated the effects of citrinin (CIT) on a yeast-transformed human DNA methyltransferase (DNMT) associated with flocculation that can be inhibited by epigenetic mutagens. CIT (0.5-2 μmol/L) inhibited the flocculation levels of yeast transfected with DNMT-genes (DNMT yeast) and the reporter gene activity of FLO1, which has been associated with flocculation. In contrast, the same concentrations of CIT had little effect on reporter activity under the control of a less methylation-sensitive FLO1 promoter. It was also shown that bacterial DNMT activity could be inhibited in the presence of CIT (4 and 40 μmol/L). These results show that CIT has inhibitory activity of DNMT, suggesting that the cytotoxicity of CIT may be involved in epigenetic mutagenicity.