Manganese-induced single strand breaks of mitochondrial DNA in vitro and in vivo.

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.