Rossman T G, Meyn M S, Troll W
Environ Health Perspect. 1977 Aug;19:229-33. doi: 10.1289/ehp.7719229.
Since environmental exposure to arsenicals has been correlated with a high skin cancer risk among populations exposed to sunlight, it is possible that arsenicals might interfere with the repair of damage to DNA (mostly thymine dimers) resulting from the ultraviolet rays in sunlight. To test this hypothesis, strains of E. coli, differing from each other only in one or more repair functions, were exposed to UV light and then plated in the presence or absence of sodium arsenite. Survival after irradiation of wild type E. coli (WP(2)) was significantly decreased by 0.5mM arsenite. This effect was also seen in strains which are unable to carry out excision repair, suggesting that arsenite inhibits one or more steps in the post-replication repair pathways. This is confirmed by the finding that arsenite has no effect on the post-irradiation survival of a recA mutant, which does not carry out post-replication repair. Mutagenesis after ultraviolet irradiation depends on the rec(+) and lex(+) genes. Arsenite decreases mutagenesis in strains containing these genes. In order to determine its mechanism of action, dose-response relationships of arsenite on a number of cellular functions were carried out. The most sensitive cellular functions found were the induction of beta-galactosidase and the synthesis of RNA. Since error-prone repair in E. coli is an inducible process, the inhibition of mutagenesis after UV irradiation may be the result of inhibition of messenger RNA synthesis.
由于在暴露于阳光的人群中,环境接触砷化合物与患皮肤癌的高风险相关,所以砷化合物可能会干扰因阳光中的紫外线导致的DNA损伤(主要是胸腺嘧啶二聚体)的修复。为了验证这一假设,将仅在一种或多种修复功能上存在差异的大肠杆菌菌株暴露于紫外线下,然后在有或没有亚砷酸钠的情况下进行平板接种。0.5mM亚砷酸钠显著降低了野生型大肠杆菌(WP(2))照射后的存活率。在无法进行切除修复的菌株中也观察到了这种效应,这表明亚砷酸盐抑制了复制后修复途径中的一个或多个步骤。这一点得到了以下发现的证实:亚砷酸盐对recA突变体照射后的存活率没有影响,recA突变体不进行复制后修复。紫外线照射后的诱变作用取决于rec(+)和lex(+)基因。亚砷酸盐降低了含有这些基因的菌株中的诱变作用。为了确定其作用机制,对亚砷酸盐对多种细胞功能的剂量反应关系进行了研究。发现最敏感的细胞功能是β-半乳糖苷酶的诱导和RNA的合成。由于大肠杆菌中的易错修复是一个可诱导的过程,紫外线照射后诱变作用的抑制可能是信使RNA合成受到抑制的结果。