Research representative: Prof. Tsuzuki, Teruhisa
(Graduate School of Medical Sciences)

@Reactive oxygen species are produced through normal cellular metabolism, and formation of such radicals is further enhanced by ionizing radiation and by various chemicals. Among various classes of DNA damage induced by oxygen radicals, an oxidized form of guanine base, 8-oxoguanine, seems to play a crucial role in carcinogenesis and aging. Organisms are equipped with elaborate mechanisms to counteract such deleterious effects of 8-oxoguanine. We have been focusing on the genes encoding enzymes those are involved in the prevention and repair of such DNA damage. In practice, we isolate cDNA and genomic clones encoding these key enzymes, characterize the protein products and use reverse genetics to develop appropriate mouse models defective in DNA repair genes.

@Gene targeting was done to establish MTH1-deficient cell lines and mice for study. When examined 18 months after birth, a greater number of tumors were formed in the lungs, livers, and stomachs of MTH1-/- mice, as compared with findings in wild-type mice. These proteins protect genetic information from untoward effects of threats of endogenous oxygen. [Ref.: Proc. Natl. Acad. Sci. USA, 98, 11456-11461, 2001]
@This work was supported, in part, by Kyushu University Interdisciplinary Programs in Education and Projects in Research Development, a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.