Zearalenone (ZEN) is a non-steroidal estrogenic mycotoxin produced by Fusarium fungi. ZEN has endocrine disruptor effects and could impair the hormonal balance. Here, we aimed at investigating possible effects of ZEN on metabolism-related pathways and its relation to epigenetic mechanisms in breast adenocarcinoma (MCF7) and breast epithelial (MCF10F) cells. Using the MTT and neutral red uptake (NRU) cell viability tests, IC₅₀ values of ZEN after 24 h were found to be 191 μmol/L and 92.6 μmol/L in MCF7 cells and 67.4 μmol/L and 79.5 μmol/L in MCF10F cells. A significant increase on global levels of 5-methylcytosine (5-mC%) was observed for MCF7 cells, correlating with the increased expression of DNA methyltransferases. No alterations were observed on levels of 5-mC% and expression of DNA methyltransferases for MCF10F cells. Further, at least threefold upregulation compared to control was observed for several genes related to nuclear receptors and metabolism in MCF7 cells, while some of these genes were downregulated in MCF10F cells. The most notably altered genes were IGF1, HK2, PXR, and PPARγ. We suggested that ZEN could alter levels of global DNA methylation and impair metabolism-related pathways.

中文翻译：

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玉米赤霉烯酮在MCF7和MCF10F细胞中引起的整体DNA甲基化和代谢相关基因的变化。

玉米赤霉烯酮（ZEN）是镰刀菌真菌产生的一种非甾体类雌激素真菌毒素。ZEN具有内分泌干扰物作用，可能会破坏荷尔蒙平衡。在这里，我们旨在调查ZEN对代谢相关途径的可能影响及其与乳腺癌细胞（MCF7）和乳腺癌上皮细胞（MCF10F）的表观遗传机制的关系。使用MTT和中性红吸收（NRU）细胞活力测试，IC ₅₀24小时后的ZEN值在MCF7细胞中为191μmol/ L和92.6μmol/ L，在MCF10F细胞中为67.4μmol/ L和79.5μmol/ L。对于MCF7细胞，观察到5-甲基胞嘧啶的总体水平显着增加（5-mC％），与DNA甲基转移酶表达的增加相关。没有观察到MCF10F细胞的5-mC％水平和DNA甲基转移酶表达的改变。此外，在MCF7细胞中，与核受体和代谢相关的几个基因与对照相比至少观察到三倍的上调，而在MCF10F细胞中，其中一些基因被下调。最显着改变的基因是IGF1，HK2，PXR和PPARγ。我们建议Z​​EN可以改变整体DNA甲基化的水平并损害与代谢相关的途径。