Abstract
Oxygen radicals are though to play an important role in mutagenesis and tumorgenesis.Among various classes of oxidative DNA damage, 8-oxo-7,8-dihydroguanine(8-oxoguanine) is most important because of its abundance and mutagenicity. In mammals, MutY homolog(MUTYH) have been detected and in vitro analysis suggested that MUTYH protein excises adenine paired with 8-oxoguanine in DNA. To investigate MUTYH function in vivo,we analyzed spontaneous tumorgenesis and mutagenesis inMutyh−/- mice.When examined 18 months after birth, a greater number of tumors were formed in different tissues,including small intestines,ofMutyh−/- mice, as compared with wild-type mice. Using the rpsL transgene as a reporter, DNA samples recovered from spleen and small intestine of these mice were analyzed for spontaneous mutation. The net frequency of rpsL forward mutants showed no apparent increase in Mutyh−/- mice as compared to Mutyh+/+mice,except for a significant increase in frequency of G:C to T:A transversion.These result suggest that MUTYH prevent mutagenesis as well as tumorgenesis caused by oxygen-induced DNA damages. [J Radiat Res 44:434 (2003)]
