Exposure to arsenic via drinking water induces 5-hydroxymethylcytosine alteration in rat.
Exposure to arsenic via drinking water induces 5-hydroxymethylcytosine alteration in rat.
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DOI：
10.1016/j.scitotenv.2014.08.009
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发表时间：
2014-11
期刊：
影响因子：
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通讯作者：
Jie Zhang;Xiaoli Mu;Weipan Xu;F. Martin;A. Alamdar;Liangpo Liu;Meiping Tian;Qingyu Huang;
中科院分区：
文献类型：
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作者：
Jie Zhang;Xiaoli Mu;Weipan Xu;F. Martin;A. Alamdar;Liangpo Liu;Meiping Tian;Qingyu Huang;
砷暴露在体外和体内均能改变DNA甲基化过程，但砷暴露是否会破坏DNA去甲基化过程这一表观遗传学调控的关键过程尚不清楚。本研究的目的是探讨砷暴露与5-甲基胞嘧啶（5 mC）和5-羟甲基胞嘧啶（5 hmC）在不同器官中的变化之间的关系。在这项研究中，我们将雄性Sprague-Dawley大鼠暴露于亚砷酸钠（0.5，2或10 ppm）通过饮用水8周。脾脏积累的砷水平比肝脏和心脏高2至3倍。肾脏、胰腺和肺中的砷含量较低。在大多数研究的器官中没有观察到显着的砷诱导的全球5 mC的变化。然而，砷诱导器官特异性改变的5 hmC和/或5 hmC/5 mC在一些被调查的器官，即肺，心脏，肾脏，胰腺和脾脏。我们的观察结果表明，5 hmC是一个更敏感的生物标志物砷诱导的影响表观遗传过程比5 mC。此外，通过羟基化5 mC的脱甲基化似乎在砷的毒性机制中起着核心作用。
Arsenic exposure has been implicated to alter DNA methylation processin vitroandin vivo, but it remains obscure whether it disrupts DNA demethylation process, which is pivotal for epigenetic regulation. The objective of this descriptive study was to investigate the relationship between arsenic exposure and 5-methylcytosine (5mC), 5-hydroxymethylcytosine (5hmC) alterations in various organs. In this study, we exposed male Sprague–Dawley rats to sodium arsenite (0.5, 2 or 10 ppm) via drinking water for 8 weeks. Spleen accumulated 2- to 3-fold higher arsenic levels than liver and heart. Lower arsenic levels were observed in the kidney, pancreas and lung. No significant arsenic-induced global 5mC alterations were observed in the majority of investigated organs. However, arsenic induced organ-specific alterations of 5hmC and/or 5hmC/5mC in some investigated organs, i.e. lung, heart, kidney, pancreas and spleen. Our observations suggest that 5hmC is a more sensitive biomarker of arsenic-induced impacts on epigenetic processes than 5mC. Moreover, demethylation via hydroxylation of 5mC appears to play a central role in the toxic mechanism of arsenic.