Triclosan reduces the levels of global DNA methylation in HepG2 cells
Triclosan reduces the levels of global DNA methylation in HepG2 cells
复制标题
三氯生降低 HepG2 细胞中整体 DNA 甲基化水平
DOI：
10.1016/j.chemosphere.2012.07.063
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发表时间：
2013-01-01
期刊：
影响因子：
8.8
通讯作者：
Fu, Jiamo
中科院分区：
文献类型：
--
作者：
Ma, Huimin;Zheng, Liujin;Fu, Jiamo
三氯生（TCS）是一种抗菌剂，广泛用于各种个人护理和工业产品。TCS与啮齿类动物肝脏肿瘤的发生有关，已成为环境和人类健康的一个问题。本研究的目的是研究TCS是否可以调节人肝细胞的DNA甲基化水平。我们发现，用不同剂量（1.25-10 μ M）的TCS处理不影响HepG 2细胞的活力，但显著降低HepG 2细胞中GDM的水平，并抑制DNMT 1活性。此外，用TCS处理显著抑制甲基化DNA结合结构域2（MBD 2）、MBD 3和MeCP 2 mRNA转录。此外，TCS处理以剂量依赖性方式促进8-羟基-2-脱氧鸟苷（8-OHdG）的积累，这被抗氧化剂N-乙酰半胱氨酸（NAC）处理所消除。总的来说，我们的数据表明，TCS降低GDM的水平，并下调MBD 2，MBD 3，和MeCP 2基因的表达，通过增加8-OHdG水平和抑制DNMT 1活性在HepG 2细胞。(C)2012爱思唯尔有限公司保留所有权利。
Triclosan (TCS), an antibacterial agent, is widely used in a variety of personal care and industrial products. TCS is associated with the development of liver tumors in rodents and has become a concern to environmental and human health. This study is aimed at investigating whether TCS could modulate the levels of global DNA methylation (GDM) in human hepatocytes. We found that treatment with different doses (1.25-10 mu M) of TCS did not affect HepG2 cell viability, but significantly reduced the levels of GDM in HepG2 cells, and inhibited DNMT1 activity. Furthermore, treatment with TCS significantly inhibited the methylated DNA-binding domain 2 (MBD2), MBD3, and MeCP2 mRNA transcription. In addition, treatment with TCS promoted the accumulation of 8-hydroxy-2-deoxyguanosine (8-OHdG) in a dose-dependent manner, which was abrogated by treatment with an antioxidant, N-acetylcysteine (NAC). Collectively, our data indicated that TCS reduced the levels of GDM and down-regulated the MBD2, MBD3, and MeCP2 gene expression by increasing 8-OHdG levels and inhibiting the DNMT1 activity in HepG2 cells. (C) 2012 Elsevier Ltd. All rights reserved.