Induction of oh(8)Gua glycosylase in rat kidneys by potassium bromate (KBrO3), a renal oxidative carcinogen

It has been suggested that 8-hydroxyguanine (oh(8)Gua), a DNA adduct formed by active oxygens, impairs the maintenance of genetic integrity. oh(8)Gua glycosylase removes oh(8)Gua residues as a free base from DNA strands. In E. coli, it has been demonstrated that oh(8)Gua glycosylase is induced in response to oxidative stress, but the oxidative inducibility in mammalian tissues has not yet been studied. In the present study, the inducibility of oh(8)Gua glycosylase was tested by comparing activity changes of this enzyme in the kidney and the liver of rats treated with potassium bromate (KBrO3). KBrO3 is known to cause oxidative damage to the kidney but not to other organs. With a single dose of KBrO3 (80 mg/kg, i.p.), activity in the kidney was found to increase significantly at 3 h compared to that at zero time. At 6 h, activity peaked, showing a 6-fold increase over that at zero time. Thereafter, it decreased and returned to its zero time level at 12 h. With increasing doses of KBrO3 (up to 160 mg/kg, i.p.), activity increased linearly with increased dosage, and over 40 mg/kg, i.p., activity increased to a level significantly higher than that in the control. In contrast to the time- and dose-dependent changes in activity in the kidney, no significant change was observed in the liver under the same conditions as above. These results show that oh(8)Gua glycosylase is also induced oxidatively in mammalian tissues. The induction in this tissue as well as in E. coli indicates that the adaptive response of this enzyme to oxidative stress is a general phenomenon in aerobic organisms and implies that the repair of oh(8)Gua residues in DNA is a process important for the survival of organisms in an aerobic environment.