Department of Environmental Health, Sichuan University, West China School of Public Health, Chengdu, People's Republic of China.
Department of Environmental Health, Sichuan University, West China School of Public Health, Chengdu, People's Republic of China.
Environ Toxicol Pharmacol. 2012 Sep;34(2):370-380. doi: 10.1016/j.etap.2012.05.012. Epub 2012 Jun 2.
Reactive oxygen species (ROS) and oxidative DNA damage have been implicated in the cigarette smoke-induced cytotoxicity and genotoxicity. DNA polymerase β (polβ), a key base excision repair (BER) enzyme in repairing oxidative DNA damage, may play a crucial role in fighting against the cytotoxicity and genotoxicity of cigarette smoke. In this study, we applied a novel approach to collect cigarette smoke extract (CSE) and investigated the cytotoxic and genotoxic effects of CSE by using the mouse embryo fibroblasts that express wild-type of polβ (polβ(+/+)), null of polβ (polβ(-/-)) and overexpression of polβ (polβ(oe)). Our results showed that polβ(-/-) cells treated with CSE exhibited a higher ROS level and more DNA single-strand breaks and chromosomal aberrations than that of polβ(+/+) and polβ(oe) cells. These data suggested that polβ mediated-BER may involve in repairing the CSE-induced DNA damage and protection against the cytotoxicity and genotoxicity of CSE.
活性氧(ROS)和氧化 DNA 损伤与香烟烟雾引起的细胞毒性和遗传毒性有关。DNA 聚合酶β(polβ)是修复氧化 DNA 损伤的关键碱基切除修复(BER)酶,可能在对抗香烟烟雾的细胞毒性和遗传毒性方面发挥关键作用。在这项研究中,我们采用了一种新方法来收集香烟烟雾提取物(CSE),并使用表达野生型 polβ(polβ(+/+))、polβ 缺失型(polβ(-/-))和过表达 polβ(polβ(oe))的小鼠胚胎成纤维细胞来研究 CSE 的细胞毒性和遗传毒性效应。我们的结果表明,与 polβ(+/+)和 polβ(oe)细胞相比,用 CSE 处理的 polβ(-/-)细胞表现出更高的 ROS 水平和更多的 DNA 单链断裂和染色体畸变。这些数据表明,polβ 介导的 BER 可能参与修复 CSE 诱导的 DNA 损伤,并防止 CSE 的细胞毒性和遗传毒性。