Binding of carbon tetrachloride metabolites to rat hepatic mitochondrial DNA

Radioactivity from [14C]CCl4 was bound to highly purified mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) prepared from livers of rats after a single dose of [14C]CCl4. At a low, non-necrotizing dose as well as at an acutely toxic dose, mtDNA bound 20-50-fold more radioactivity per mg than did nDNA. Extensive enzymatic digestion and purification of mtDNA did not remove radioactivity. Binding of radioactivity to mtDNA could also be demonstrated after anaerobic incubation of isolated mitochondria with [14C]CCl4, NADPH, ADP, and succinate. Our results suggest that CCl4 can be activated by rat hepatic mitochondrial enzymes to metabolites which bind covalently to mtDNA.