Cortex and hippocampus DNA epigenetic response to a long-term arsenic exposure via drinking water

被引：46

作者：

Du, Xiaoyan ^{[1
,2
]}

Tian, Meiping ^{[1
,2
]}

Wang, Xiaoxue ^{[1
]}

Zhang, Jie ^{[1
,3
]}

Huang, Qingyu ^{[1
]}

Liu, Liangpo ^{[1
]}

Shen, Heqing ^{[1
]}

机构：

[1] Chinese Acad Sci, Inst Urban Environm, Key Lab Urban Environm & Hlth, Beijing, Peoples R China

[2] Univ Chinese Acad Sci, Beijing, Peoples R China

[3] Jinan Univ, Sch Environm, Guangzhou Key Lab Environm Exposure & Hlth, Guangzhou, Guangdong, Peoples R China

来源：

ENVIRONMENTAL POLLUTION | 2018年 / 234卷

基金：

中国国家自然科学基金;

关键词：

Arsenic; DNA epigenetics; Oxidative stress; DNA methyltransferases; Ten-eleven translocations; OXIDATIVE DAMAGE; INTELLECTUAL FUNCTION; ANTIOXIDANT ENZYMES; NERVOUS-SYSTEM; METHYLATION; 5-HYDROXYMETHYLCYTOSINE; BRAIN; GLUTATHIONE; REDUCTION; PROTEINS;

D O I：

10.1016/j.envpol.2017.11.083

中图分类号：

X [环境科学、安全科学];

学科分类号：

08 ; 0830 ;

摘要：

The neurotoxicity of arsenic is a serious health problem, especially for children. DNA epigenetic change may be an important pathogenic mechanism, but the molecular pathway remains obscure. In this study, the weaned male Sprague-Dawly (SD) rats were treated with arsenic trioxide via drinking water for 6 months, simulating real developmental exposure situation of children. Arsenic exposure impaired the cognitive abilities, and altered the expression of neuronal activity-regulated genes. Total arsenic concentrations of cortex and hippocampus tissues were significantly increased in a dose-dependent manner. The reduction in 5-methylcytosine (5 mC) and 5-hydroxymethylcytosine (5hmC) levels as well as the down-regulation of DNA methyltransferases (DNMTs) and ten-eleven translocations (TETs) expression suggested that DNA methylation/demethylation processes were significantly suppressed in brain tissues. S-adenosylmethionine (SAM) level wasn't changed, but the expression of the important indicators of oxidative/anti-oxidative balance and tricarboxylic acid (TCA) cycle was significantly deregulated. Overall, arsenic can disrupt oxidative/anti-oxidative balance, further inhibit TETs expression through TCA cycle and alpha-ketoglutarate (alpha-KG) pathway, and consequently cause DNA methylation/demethylation disruption. The present study implies oxidative stress but not SAM depletion may lead to DNA epigenetic alteration and arsenic neurotoxicity. (C) 2017 Elsevier Ltd. All rights reserved.

引用

页码：590 / 600

页数：11

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