Department of Toxicology, Peking University Health Science Center, Beijing 100083, PR China.
Environ Toxicol Pharmacol. 2008 Sep;26(2):123-7. doi: 10.1016/j.etap.2007.12.009. Epub 2008 Feb 14.
The aim of this study was to examine the single strand breaks (SSB) of mitochondrial DNA (mtDNA) induced by MnCl(2) in vitro and in vivo and discuss the possible underlying mechanism. In in vitro study the formation of mtDNA SSB and reactive oxygen species (ROS) in isolated hepatic mitochondria treated with MnCl(2) (0-1.0mmolL(-1)) was observed. In in vivo study the SSB of brain and liver mtDNA was examined, meanwhile the level of glutathione (GSH) and malondialdehyde (MDA) and activity of antioxidant enzymes were examined after 3-month intraperitoneal administration of MnCl(2) daily (0, 5, 10 and 20mg/kg/d) in Sprague-Dawley rats. The in vitro results indicated that MnCl(2) increased the formation of mtDNA SSB and ROS in **a dose-dependent manner in vitro. MnCl(2) exposure in vivo increased in mtDNA SSB in rat brain and liver and decreased in level of GSH in rat hepatic mitochondria and brain homogenates in a dose-dependent manner. The level of MDA and the activities of SOD and GPx were not significantly changed in both hepatic mitochondria and brain homogenates of rats. These results indicated that Mn treatment increased in mtDNA SSB in vitro and in vivo, mediated probably via Mn-induced oxidative stress.
本研究旨在探讨 MnCl2 在体外和体内诱导的线粒体 DNA（mtDNA）单链断裂（SSB）及其可能的机制。在体外研究中，观察了不同浓度 MnCl2（0-1.0mmol/L）处理的分离肝线粒体中 mtDNA SSB 和活性氧（ROS）的形成。在体内研究中，检测了 MnCl2（0、5、10 和 20mg/kg/d）腹腔注射 3 个月后大鼠脑和肝线粒体 mtDNA 的 SSB，同时检测了大鼠肝线粒体和脑组织匀浆中谷胱甘肽（GSH）和丙二醛（MDA）水平以及抗氧化酶活性的变化。结果表明，MnCl2 能在线粒体中以剂量依赖的方式增加 mtDNA SSB 和 ROS 的形成。MnCl2 体内暴露能使大鼠脑和肝 mtDNA 的 SSB 增加，肝线粒体和脑匀浆中的 GSH 水平降低，呈剂量依赖性。肝线粒体和脑匀浆中 MDA 水平以及 SOD 和 GPx 活性无明显变化。这些结果表明，Mn 处理能在线粒体和体内增加 mtDNA SSB，可能是通过 Mn 诱导的氧化应激介导的。
