Levels of DNA damage are unaltered in mice overexpressing human catalase in nuclei

Two types of transgenic mice were generated to evaluate the role of hydroge n peroxide in the formation of nuclear DNA damage. One set of lines overexp resses wild-type human catalase cDNA, which is localized to peroxisomes. Th e other set overexpresses a human catalase construct that is targeted to th e nucleus. Expression of the wild-type human catalase transgene was found i n liver, kidney, skeletal muscle, heart, spleen, and brain with muscle and heart exhibiting the highest levels. Animals containing the nuclear-targete d construct had a similar pattern of expression with the highest levels in muscle and heart, but with lower levels in liver and spleen. In these anima ls, immunofluorescence detested catalase present in the nuclei of kidney, m uscle, heart, and brain. Both types of transgenic animals had significant i ncreases of catalase activities compared to littermate controls in most tis sues examined. Despite enhanced activities of catalase, and its presence in the nucleus, there were no changes in levels of 8OHdG, a marker of oxidati ve damage to DNA. Nor were there differences in mutant frequencies at a Lac Z reporter transgene. This result suggests that in vivo levels of H2O2 may not generate 8OHdG or other types of DNA damage. Alternatively, antioxidan t defenses may be optimized such that additional catalase is unable to furt her protect nuclear DNA against oxidative damage. (C) 2000 Elsevier Science Inc.