Inhibition of DNA ligase activity by arsenite: a possible mechanism of its comutagenesis.

Molecular toxicology Pub Date : 1989-01-01
J H Li, T G Rossman
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Abstract

We have previously shown that the inhibition of MNU-induced DNA repair by arsenite occurs after the incision step in Chinese hamster V79 cells. We now report that nuclear DNA ligase activity is inhibited after arsenite treatment and that the inhibited activity is mostly DNA ligase II. Both constitutive and MNU-inducible levels of DNA ligase II are inhibited. The addition of arsenite in vitro also indicates that DNA ligase II is more sensitive to arsenite inhibition than DNA ligase I. Since DNA ligase II is reported to be involved in the ligation step of excision repair, its inhibition by arsenite is a likely mechanism for the inhibition of DNA repair by arsenite and may account for the fact that arsenite acts as a comutagen with a number of different types of mutagens. The carcinogenicity of arsenite may also be a result of ligase inhibition.

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亚砷酸盐对DNA连接酶活性的抑制:其突变发生的可能机制。
我们之前的研究表明,亚砷酸盐对mnu诱导的DNA修复的抑制发生在中国仓鼠V79细胞的切口步骤之后。我们现在报道核DNA连接酶活性在亚砷酸盐处理后被抑制,并且被抑制的活性主要是DNA连接酶II。DNA连接酶II的组成型和mnu诱导型水平均受到抑制。体外添加亚砷酸盐也表明,DNA连接酶II对亚砷酸盐的抑制比DNA连接酶i更敏感。由于DNA连接酶II被报道参与了切除修复的连接步骤,亚砷酸盐对其的抑制可能是亚砷酸盐抑制DNA修复的一种机制,这可能解释了亚砷酸盐与许多不同类型的诱变剂起致变剂作用的原因。亚砷酸盐的致癌性也可能是连接酶抑制的结果。
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Xenobiotic regulation of glutathione S-transferase Ya gene expression. Review: gene amplification--a cellular response to genotoxic stress. Limitations of the fluorescent probe viability assay. Induction of a novel damage-specific DNA binding protein correlates with enhanced DNA repair in primate cells. Induction of a novel damage-specific DNA binding protein correlates with enhanced DNA repair in primate cells.
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