Zearalenone, produced by various Fusarium species, is a non-steroidal estrogenic mycotoxin that contaminates cereals, resulting in adverse effects on human health. We investigated the effects of zearalenone and its metabolite alpha zearalenol on epigenetic modifications and its relationship with metabolic pathways in human hepatocellular carcinoma cells following 24 h of exposure. Zearalenone and alpha zearalenol at the concentrations of 1, 10 and 50 µM significantly increased global levels of DNA methylation and global histone modifications (H3K27me3, H3K9me3, H3K9ac). Expression levels of the chromatin modifying enzymes EHMT2, ESCO1, HAT1, KAT2B, PRMT6 and SETD8 were upregulated by 50 µM of zearalenone exposure using PCR arrays, consistent with the results of global histone modifications. Zearalenone and alpha zearalenol also changed expression levels of the AhR, LXRα, PPARα, PPARɣ, L-fabp, LDLR, Glut2, Akt1 and HK2 genes, which are related to nuclear receptors and metabolic pathways. PPARɣ, a key regulator of lipid metabolism, was selected from among these genes for further analysis. The PPARɣ promoter reduced methylation significantly following zearalenone exposure. Taken together, the epigenetic mechanisms of DNA methylation and histone modifications may be key mechanisms in zearalenone toxicity. Furthermore, effects of zearalenone in metabolic pathways could be mediated by epigenetic modifications.

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评价暴露于玉米赤霉烯酮和α-玉米赤霉烯醇的 HepG2 细胞的表观遗传改变和基因表达水平

玉米赤霉烯酮由各种镰刀菌属植物产生，是一种非甾体雌激素霉菌毒素，会污染谷物，对人类健康造成不利影响。我们研究了玉米赤霉烯酮及其代谢物 α 玉米赤霉烯醇对表观遗传修饰的影响及其与暴露 24 小时后人肝细胞癌细胞代谢途径的关系。浓度为 1、10 和 50 µM 的玉米赤霉烯酮和 α 玉米赤霉烯醇显着增加了 DNA 甲基化和全局组蛋白修饰（H3K27me3、H3K9me3、H3K9ac）的整体水平。染色质修饰酶 EHMT2、ESCO1、HAT1、KAT2B、PRMT6 和 SETD8 的表达水平通过使用 PCR 阵列暴露 50 µM 玉米赤霉烯酮而上调，这与全局组蛋白修饰的结果一致。玉米赤霉烯酮和 α 玉米赤霉烯醇还改变了与核受体和代谢途径相关的 AhR、LXRα、PPARα、PPARɣ、L-fabp、LDLR、Glut2、Akt1 和 HK2 基因的表达水平。PPARɣ是脂质代谢的关键调节因子，从这些基因中被挑选出来进行进一步分析。PPARɣ 启动子在暴露玉米赤霉烯酮后显着降低了甲基化。总之，DNA甲基化和组蛋白修饰的表观遗传机制可能是玉米赤霉烯酮毒性的关键机制。此外，玉米赤霉烯酮在代谢途径中的作用可能由表观遗传修饰介导。从这些基因中选出进行进一步分析。PPARɣ 启动子在暴露玉米赤霉烯酮后显着降低了甲基化。总之，DNA甲基化和组蛋白修饰的表观遗传机制可能是玉米赤霉烯酮毒性的关键机制。此外，玉米赤霉烯酮在代谢途径中的作用可以通过表观遗传修饰介导。从这些基因中选出进行进一步分析。PPARɣ 启动子在暴露玉米赤霉烯酮后显着降低了甲基化。总之，DNA甲基化和组蛋白修饰的表观遗传机制可能是玉米赤霉烯酮毒性的关键机制。此外，玉米赤霉烯酮在代谢途径中的作用可能由表观遗传修饰介导。