Possible participation of oxidative stress in causation of cell proliferation and in vivo mutagenicity in kidneys of gpt delta rats treated with potassium bromate

Clarifying the participation of oxidative stress among possible contributing factors in potassium bromate (KBrO3)-induced carcinogenesis is of importance from the perspective of human health protection. In the present study, utilizing the antioxidative effects of α-tocopherol (α-TP) or sodium ascorbic acid (SAA) to attenuate oxidative stress, alterations in bromodeoxyuridine labeling indices (BrdU-LIs) and reporter gene mutations in kidneys of male and female gpt delta rats given KBrO3 were examined. Five male and female gpt delta rats in each group were given KBrO3 at a concentration of 500 ppm in the drinking water for 9 weeks, with 1% of α-TP or SAA administered in the diet from 1 week prior to the KBrO3 treatment until the end of the experiment. Increases in 8-hydroxydeoxyguanosine levels in kidney DNA of both sexes of rats given KBrO3 were significantly inhibited by SAA, but not α-TP. While BrdU-LIs in the proximal tubules of female rats were also significantly reduced by SAA, those in the males and gpt mutant frequencies in kidney DNA of both sexes were not affected by SAA or α-TP. Immunohistochemical and Western blot analyses for α2u-globulin strongly suggested that induction of cell proliferation observed in the males might primarily result from accumulation of this protein, independent of oxidative stress. The overall data indicated that while oxidative stress well correlates with induction of cell proliferation in females, its role in males and in generation of in vivo mutagenicity by KBrO3 in both sexes is limited.