Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Istanbul University, 34116-Beyazit, Istanbul, Turkey.
Mycotoxin Res. 2019 Aug;35(3):309-320. doi: 10.1007/s12550-019-00358-8. Epub 2019 Apr 5.
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, IC 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.
玉米赤霉烯酮（ZEN）是一种由镰刀菌产生的非甾体类雌激素真菌毒素。ZEN 具有内分泌干扰作用，可能会破坏激素平衡。在这里，我们旨在研究 ZEN 对代谢相关途径的可能影响及其与乳腺癌腺癌细胞（MCF7）和乳腺上皮细胞（MCF10F）中表观遗传机制的关系。使用 MTT 和中性红摄取（NRU）细胞活力测试，发现 ZEN 在 MCF7 细胞中的 24 小时 IC 值为 191 μmol/L 和 92.6 μmol/L，在 MCF10F 细胞中的为 67.4 μmol/L 和 79.5 μmol/L。MCF7 细胞中观察到 5-甲基胞嘧啶（5-mC%）的总体水平显著增加，这与 DNA 甲基转移酶的表达增加有关。MCF10F 细胞中 5-mC%和 DNA 甲基转移酶的水平没有观察到变化。此外，与对照组相比，MCF7 细胞中与核受体和代谢相关的几个基因的表达至少上调了三倍，而在 MCF10F 细胞中，其中一些基因下调。变化最显著的基因是 IGF1、HK2、PXR 和 PPARγ。我们认为，ZEN 可能会改变全基因组 DNA 甲基化水平并损害代谢相关途径。
