Increased liver-specific catalase activity in transgenic mice

Catalase is the major peroxisomal H2O2-detoxifying enzyme and is thought to be critical in maintaining low H2O2 levels within a cell. It has been proposed that increased H2O2 levels may be involved in oxidative DNA damage and tumor promotion induced by peroxisome proliferators and other xenobiotics. To develop a mouse model system to address this issue, we have generated transgenic mice that exhibit a three- to four-fold increase in liver catalase levels. The activities of fatty acyl coenzyme A (CoA) oxidase and lauric acid hydroxylase were unchanged in transgenic mice, demonstrating that elevated catalase levels did not alter the activity of these other peroxisome proliferator-induced enzymes that produce active oxygen. These mice should help elucidate the role of H2O2 in cellular events mediated by peroxisome proliferators and other xenobiotics.