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饮用含重铬酸钾的水的雄性Sprague-Dawley大鼠出现组织铬水平升高、血浆氧化标志物增加以及血液DNA整体低甲基化。

Elevated tissue Cr levels, increased plasma oxidative markers, and global hypomethylation of blood DNA in male Sprague-Dawley rats exposed to potassium dichromate in drinking water.

作者信息

Wang Yu, Wu Wei, Yao Chunji, Lou Jianlin, Chen Riping, Jin Lingzhi, Wu Nanxiang, Gao Ming, Song Peng, Tan Yufeng, Liu Kecheng

机构信息

Institute of Occupational Disease, Zhejiang Academy of Medical Sciences, Hangzhou, Zhejiang, People's Republic of China.

Eye Center, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China; and Zhejiang Provincial Key Lab of Ophthalmology, Hangzhou, China.

出版信息

Environ Toxicol. 2016 Sep;31(9):1080-90. doi: 10.1002/tox.22117. Epub 2015 Apr 6.

Abstract

Hexavalent chromium [Cr (VI)] is prevalent in ground water in some areas, but evidence on the toxic effects of Cr (VI) via ingestion through drinking water remains insufficient. The aims of our study were to investigate the toxic effects of Cr (VI) through oral water ingestion on oxidative stress and DNA methylation. Thirty-two Sprague-Dawley rats were randomly divided into four groups, and exposed to porassium dichromate (K2 Cr2 O7 ; 0, 30, 100, and 300 mg/L) in drinking water for 4 weeks. Mean body weight gain, mean water consumption, clinical chemistry determinations, and oxidative stress levels in plasma were measured. Global DNA methylation changes and DNA methylation status at the promoter of p16 gene were also detected. After 4 weeks, mild anemic effects and increased plasma malondialdehyde (MDA) levels occurred in rats exposed to 100 mg/L or 300 mg/L of Cr (VI). Plasma glutathione peroxidase (GSH-Px) activity decreased in all exposed groups. Global DNA methylation levels were reduced in 100 mg/L and 300 mg/L exposure groups. However, DNA methylation status at the promoter of P16 gene remained unchanged in all K2 Cr2 O7- treated groups. The correlation analysis indicated that increased MDA levels were closely correlated to global DNA hypomethylation. Our results indicated that oral ingestion of Cr (VI) through drinking water caused not only oxidative stress in plasma, but also global DNA hypomethylation in blood cells from male rats, and a good correlation was found between increased MDA levels and reduced global DNA methylation. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1080-1090, 2016.

摘要

六价铬[Cr(VI)]在一些地区的地下水中普遍存在,但关于通过饮用水摄入Cr(VI)的毒性作用的证据仍然不足。我们研究的目的是调查通过口服饮水摄入Cr(VI)对氧化应激和DNA甲基化的毒性作用。将32只Sprague-Dawley大鼠随机分为四组,在饮用水中暴露于重铬酸钾(K2Cr2O7;0、30、100和300mg/L)4周。测量平均体重增加、平均饮水量、临床化学测定以及血浆中的氧化应激水平。还检测了整体DNA甲基化变化和p16基因启动子处的DNA甲基化状态。4周后,暴露于100mg/L或300mg/L Cr(VI)的大鼠出现轻度贫血效应和血浆丙二醛(MDA)水平升高。所有暴露组的血浆谷胱甘肽过氧化物酶(GSH-Px)活性均降低。100mg/L和300mg/L暴露组的整体DNA甲基化水平降低。然而,所有K2Cr2O7处理组中p16基因启动子处的DNA甲基化状态保持不变。相关性分析表明,MDA水平升高与整体DNA低甲基化密切相关。我们的结果表明,通过饮用水口服摄入Cr(VI)不仅会导致血浆中的氧化应激,还会导致雄性大鼠血细胞中的整体DNA低甲基化,并且MDA水平升高与整体DNA甲基化降低之间存在良好的相关性。©2015威利期刊公司。环境毒理学31:1080 - 1090,2016。

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