Reduction of arsenite-enhanced ultraviolet radiation-induced DNA damage by supplemental zinc.
Reduction of arsenite-enhanced ultraviolet radiation-induced DNA damage by supplemental zinc.
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DOI：
10.1016/j.taap.2013.03.008
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发表时间：
2013-06-01
影响因子：
3.8
通讯作者：
Hudson, Laurie G.
中科院分区：
文献类型：
--
作者：
Cooper, Karen L.;King, Brenee S.;Sandoval, Monica M.;Liu, Ke Jian;Hudson, Laurie G.
砷是一种公认的人类致癌物，有证据表明，砷增加了DNA损伤剂（如紫外线辐射（UVR））的致癌性，从而作为一种共同致癌物。抑制DNA修复是一种被提出的解释砷的共同致癌作用的机制。我们和其他人发现亚砷酸盐干扰某些锌指DNA修复蛋白的功能。此外，我们报道了锌逆转培养细胞中亚砷酸盐和DNA修复靶蛋白聚（ADP-核糖）聚合酶-1的作用。为了确定锌是否改善砷对紫外线诱导的人角质形成细胞DNA损伤的影响，在体内模型中，正常人表皮角质形成细胞和SKH-1无毛小鼠在太阳模拟（SS）紫外线暴露前暴露于砷，锌或两者。在正常人角质形成细胞中，在每个处理组中测量聚（ADP-核糖）聚合酶活性、DNA损伤和hprt位点的突变频率。通过对SKH-1无毛小鼠分离的皮肤切片进行免疫组织化学染色，在体内评估DNA损伤。基于细胞的研究结果表明，亚砷酸盐会增强ssUVR诱导的DNA损伤和突变，而补充锌可以部分逆转亚砷酸盐的作用。体内研究证实，锌补充剂降低砷增强的DNA损伤响应ssUVR暴露。从这些数据中，我们可以得出结论，锌抵消了砷对ssUVR刺激的DNA损伤的影响，在细胞和体内表明，锌补充剂可能提供一种策略，以提高砷暴露人群的DNA修复能力。
Arsenic is a recognized human carcinogen and there is evidence that arsenic augments the carcinogenicity of DNA damaging agents such as ultraviolet radiation (UVR) thereby acting as a co-carcinogen. Inhibition of DNA repair is one proposed mechanism to account for the co-carcinogenic actions of arsenic. We and others find that arsenite interferes with the function of certain zinc finger DNA repair proteins. Furthermore, we reported that zinc reverses the effects of arsenite in cultured cells and a DNA repair target protein, poly (ADP-ribose) polymerase-1. In order to determine whether zinc ameliorates the effects of arsenite on UVR-induced DNA damage in human keratinocytes and in an in vivo model, normal human epidermal keratinocytes and SKH-1 hairless mice were exposed to arsenite, zinc or both before solar-simulated (ss) UVR exposure. Poly (ADP-ribose) polymerase activity, DNA damage and mutation frequencies at the hprt locus were measured in each treatment group in normal human keratinocytes. DNA damage was assessed in vivo by immunohistochemical staining of skin sections isolated from SKH-1 hairless mice. Cell-based findings demonstrate that ssUVR-induced DNA damage and mutagenesis are enhanced by arsenite, and supplemental zinc partially reverses the arsenite effect. In vivo studies confirm that zinc supplementation decreases arsenite-enhanced DNA damage in response to ssUVR exposure. From these data we can conclude that zinc offsets the impact of arsenic on ssUVR-stimulated DNA damage in cells and in vivo suggesting that zinc supplementation may provide a strategy to improve DNA repair capacity in arsenic exposed human populations.
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影响因子：
4.1
作者：
Qin, Xu-Jun;Hudson, Laurie G.;Liu, Wenlan;Ding, Wei;Cooper, Karen L.;Liu, Ke Han
通讯作者：
Liu, Ke Han
影响因子：
6.4
作者：
Hartwig, A;Pelzer, A;Bürkle, A
通讯作者：
Bürkle, A
影响因子：
3.9
作者：
Kitchin, Kirk T.;Wallace, Kathleen
通讯作者：
Wallace, Kathleen
影响因子：
4.8
作者：
Ding, Wei;Liu, Wenlan;Liu, Ke Jian
通讯作者：
Liu, Ke Jian
DOI：
10.1016/s1383-5718(02)00057-8
发表时间：
2002-05-27
影响因子：
1.9
作者：
Maier, A;Schumann, BL;Puga, A
通讯作者：
Puga, A