Abstract
DNA pyrimidines are continuously oxidized in physiological condition. Because the productive damaged pyrimidines can result in tumor formation, they are thought to be repaired majorly with single nucleotide-base excision repair (SN-BER) pathway. The mammalian homologs of endonuclease III and endonuclease VIII, Nthl1 and Neil1, are known as oxidized pyrimidine-DNA glycosylases, and thought to have a major contribution to remove oxidized pyrimidines in mammals. We found an unidentified monofunctional thymine glycol (TG)-DNA glycosylase (TGG) activity in nuclei of mouse organs. As mouse spleen, stomach and lung, showed higher TGG activity than liver, it is suggested that TGG activity may play a role mainly in proliferative organs. This suggestion is supported an idea that strong apurinic/apyrimidinic (AP) lyase activities accompanied with Nthl1 and Neil1 may be deleterious in a nuclear of a proliferating cell. It is reasonable that the TGG activity exists in various mammals, including mouse. The similar genome sizes of mouse, monkey, human are 3.3x109, 3.0x109, 3.0x109 base pairs, respectively. On the other hand, the life spans are very difficult; about 3, 30 and 90 years, respectively. The level of TG in urine is correlated with life span (Adelman R. et al., 1988, Proc. Natl. Acad. Sci. USA), suggesting that the difference of life span is associated with that of TG removal activity and a repair mechanism. Recently, with an elongation of dog life span, the incidence for canine cancers has been increasing. It is expected that the level of TG removal activity in canine is lower than that in mouse. In this report, we show that the specific activity of TGG in canine liver is low to 67% of that in mouse liver.
