Arsenic exposure is associated with decreased DNA repair in vitro and in individuals exposed to drinking water arsenic.
Arsenic exposure is associated with decreased DNA repair in vitro and in individuals exposed to drinking water arsenic.
复制标题
DOI：
10.1289/ehp.9008
复制
发表时间：
2006-08
影响因子：
10.4
通讯作者：
Karagas MR
中科院分区：
文献类型：
--
作者：
Andrew AS;Burgess JL;Meza MM;Demidenko E;Waugh MG;Hamilton JW;Karagas MR
砷暴露导致人类癌症风险的机制尚不清楚;然而，已经提出了几种间接的致癌机制。许多研究支持As在改变一个或多个DNA修复过程中的作用。在本研究中，我们使用个人水平的暴露数据和生物样本，以调查在两个研究人群中的核苷酸切除修复的影响，重点切除修复交叉补体1（ERCC 1）组件。我们测量饮用水，尿液，或趾甲As水平，并获得冷冻保存的淋巴细胞的一个子集的个人参加流行病学研究在新罕布什尔州（美国）和索诺拉（墨西哥）。此外，在确证的实验室研究中，我们研究了在培养的人类细胞模型中As对DNA修复的影响。砷暴露与ERCC 1在mRNA和蛋白水平上的表达降低有关。此外，从作为暴露的个人淋巴细胞表现出较高水平的DNA损伤，彗星试验测定，无论是在基线和2-乙酰氧基乙酰氨基芴（2-AAAF）的挑战。在体内数据的支持下，在细胞培养中，2-AAAF激发后，As暴露降低了ERCC 1 mRNA表达并增强了DNA损伤水平。这些数据提供了进一步的证据，以支持作为抑制DNA修复机制的能力，这可能会提高其他直接遗传毒性化合物的遗传毒性和致突变性，作为一个致癌作用机制的一部分。
The mechanism(s) by which arsenic exposure contributes to human cancer risk is unknown; however, several indirect cocarcinogenesis mechanisms have been proposed. Many studies support the role of As in altering one or more DNA repair processes. In the present study we used individual-level exposure data and biologic samples to investigate the effects of As exposure on nucleotide excision repair in two study populations, focusing on the excision repair cross-complement 1 (ERCC1) component. We measured drinking water, urinary, or toenail As levels and obtained cryopreserved lymphocytes of a subset of individuals enrolled in epidemiologic studies in New Hampshire (USA) and Sonora (Mexico). Additionally, in corroborative laboratory studies, we examined the effects of As on DNA repair in a cultured human cell model. Arsenic exposure was associated with decreased expression of ERCC1 in isolated lymphocytes at the mRNA and protein levels. In addition, lymphocytes from As-exposed individuals showed higher levels of DNA damage, as measured by a comet assay, both at baseline and after a 2-acetoxyacetylaminofluorene (2-AAAF) challenge. In support of the in vivo data, As exposure decreased ERCC1 mRNA expression and enhanced levels of DNA damage after a 2-AAAF challenge in cell culture. These data provide further evidence to support the ability of As to inhibit the DNA repair machinery, which is likely to enhance the genotoxicity and mutagenicity of other directly genotoxic compounds, as part of a cocarcinogenic mechanism of action.
登录
查看更多内容
影响因子：
5
作者：
Karagas, MR;Tosteson, TD;Morris, JS
通讯作者：
Morris, JS
影响因子：
3.8
作者：
Liu, J;Kadiiska, MB;Waalkes, MP
通讯作者：
Waalkes, MP
影响因子：
4.7
作者：
Baltaci, V;Kayikçioglu, F;Haberal, A
通讯作者：
Haberal, A
DOI：
10.1007/bf02036470
发表时间：
1995-08-01
期刊：
JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY-ARTICLES
影响因子：
--
作者：
CHENG, TP;MORRIS, JS;BASKETT, CK
通讯作者：
BASKETT, CK
DOI：
10.1080/152873901316857789
发表时间：
2001-08-01
期刊：
JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A
影响因子：
--
作者：
Curnow, A;Salter, L;Gould, D
通讯作者：
Gould, D