Subchronic exposure to arsenic trioxide-induced oxidative DNA damage in kidney tissue of mice

Subchronic exposure to arsenic trioxide-induced oxidative DNA damage in kidney tissue of mice
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DOI:
10.1016/j.etp.2009.07.003
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发表时间:
2010-09-01
影响因子:
--
通讯作者:
Qu, Shuxian
Qu, Shuxian
中科院分区:
医学2区
文献类型:
--
作者:
Li, Zongyuan;Piao, Fengyuan;Qu, Shuxian

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为探讨三氧化二砷(As_2O_3)亚慢性染毒对小鼠肾组织DNA氧化损伤的影响,观察了8-羟基脱氧鸟苷(8-OHdG)的表达及病理变化。将40只小鼠随机分为4组,每组10只(每种性别5只小鼠)。第1组仅给予饮用水(对照)。第2、3和4组分别接受1、2和4 mg/L的三氧化二砷。三氧化二砷通过饮用水给药60天。分析4组小鼠肾组织中8-OHdG的表达情况。砷处理组肾组织病理改变明显,8-OHdG表达水平明显升高(P < 0.01)。此外,砷暴露与肾脏损害之间的剂量依赖性增加。尤其是近曲小管和Bowman囊的免疫活性较强。提示慢性砷暴露可引起肾组织损伤,尤其是近曲小管上皮细胞和Bowman囊足细胞对砷的肾毒性更为敏感。(C)2009年Elsevier GmbH。All rights reserved.
To evaluate the oxidative DNA damage in kidney tissue of mice exposed to arsenic trioxide (As) subchronically, expression of 8-hydroxy-2-deoxyguanosine (8-OHdG) and pathologic changes were observed. Forty mice were randomly divided into 4 groups of 10 each (5 mice of each sex). Group 1 received drinking water alone (control). Groups 2, 3 and 4 received 1, 2 and 4 mg/L arsenic trioxide, respectively. Arsenic trioxide was given through drinking water for 60 days. The expression of 8-OHdG in the kidney tissue of mice was analyzed observed in these 4 groups. The groups treated with As showed pathologic changes in the kidney tissue and significant increase in the level of 8-OHdG expression (P < 0.01). Moreover, the dose-dependent increase between As exposure and renal damages were observed. Especially, its immunoactivity was strong in the proximal convoluted tubule and Bowman's capsule. These results suggest that chronic exposure to As induces damages to kidney tissue, and especially the epithelial cells of proximal convoluted tubule and the podocytes of the Bowman's capsule may be more sensitive to As-induced nephrotoxicity. (C) 2009 Elsevier GmbH. All rights reserved.