摘要
采用纯化酶活性分析和人细胞体外培养方法 ,研究砷对人 DNA修复关键酶—— DNA连接酶活性的影响。结果表明 :纯化人 DNA连接酶 和 在毫摩尔水平三价砷和五价砷存在下 ,酶活性增加。与此不同的是 ,经过微摩尔砷处理的人细胞核提取物的 DNA连接酶的活性即可被显著抑制。未经染砷处理的细胞核提取物的 DNA连接酶活性与纯化酶对砷的敏感性没有显著区别。说明砷的毒性与砷对 DNA连接酶的作用没有直接联系。因此 ,砷的促突变和对 DNA’损伤后修复的抑制 ,可能并非直接抑制修复酶所致 ,可能与砷所引起的细胞内信号传递和基因表达的改变及通过转录水平或翻译修饰的调节有关。
The effect of arsenic on human DNA Ligase one of key enzyme of DNA repair, was studied by using purified enzymes and human cells in culture. Results showed that the purified Ligase activity was not inhibited by less than milimorlar concentration of arsenic. In striking contrast to that in vitro study, we found that treatment of cultured human cells with less than 5.0 μM As(Ⅲ) caused a dose dependent decrease in Ligase activity, while Ligase activity in extracts from untreated cells was not sensitive to less than 1 mM As(Ⅲ). These results clearly demonstrated that the two most critical human DNA Ligase, Ligase I and Ligase Ⅲ were not directly inhibited by As (Ⅲ) and As (Ⅴ) and suggested that As might inhibit DNA repair and Ligastion by an indirect mechanism, possibly through changes in signal transduction pathway and gene expression or transcription and posttranslation modification of Ligase.
出处
《地方病通报》
2000年第1期7-10,共4页
Endemic Diseases Bulletin
基金
美国国家环保署 (EPA)项目
关键词
砷
DNA连接酶
肿瘤
Arsenic
Human cells
DNA Ligase
