Very low concentrations of arsenite suppress poly(adp-ribosyl)ation in mammalian cells
Very low concentrations of arsenite suppress poly(adp-ribosyl)ation in mammalian cells
复制标题
DOI：
10.1002/ijc.10911
复制
发表时间：
2003-03-10
影响因子：
6.4
通讯作者：
Bürkle, A
中科院分区：
文献类型：
--
作者：
Hartwig, A;Pelzer, A;Bürkle, A
亚砷酸盐是一种天然存在的环境污染物，引起了人们的严重关注，因为长期接触砷，特别是通过饮用水接触砷，会对健康产生不良影响，包括皮肤癌和内脏癌。亚砷酸盐不是点突变的重要诱导物，但在低微摩尔浓度范围内，它具有致染色体断裂活性并干扰各种DNA修复系统。然而，没有一个DNA修复蛋白对砷非常敏感。在这里，我们报告说，聚（ADP-核糖）的作用，这主要是由聚（ADP-核糖）聚合酶-1（PARP-1）介导的，抑制浓度低至10纳米培养的HeLa细胞，密切匹配砷浓度在血液和尿液中的一般人群。由于聚（ADP-核糖基）化是对DNA损伤的直接细胞反应，在DNA碱基切除修复和维持基因组稳定性中起着重要作用，亚砷酸盐对其的抑制可能会增加低暴露条件下癌症形成的风险。(C)2002 Wiley-Liss，Inc.
Arsenite is a naturally occurring environmental pollutant of major concern, since adverse health effects including cancer of skin and internal organs have been attributed to chronic arsenic exposure especially via drinking water. Arsenite is not a significant inducer of point mutations but exerts clastogenic activities and interferes with various DNA repair systems at concentrations in the low micromolar range. Nevertheless, no single DNA repair protein exquisitely sensitive to arsenic has been identified. Here we report that poly(ADP-ribosyl)ation, which is predominantly mediated by poly(ADP-ribose) polymerase-1 (PARP-1), is inhibited at concentrations as low as 10 nM in cultured HeLa cells, closely matching arsenic concentrations in blood and urine of the general population. Since poly(ADP-ribosyl)ation is an immediate cellular response to DNA damage, playing a major role in DNA base excision repair and the maintenance of genomic stability, its inhibition by arsenite may add to the risk of cancer formation under low-exposure conditions. (C) 2002 Wiley-Liss, Inc.