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 (KBrO(3))-induced carcinogenesis is of importance from the perspective of human health protection. In the present study, utilizing the antioxidative effects of alpha-tocopherol (alpha-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 KBrO(3) were examined. Five male and female gpt delta rats in each group were given KBrO(3) at a concentration of 500ppm in the drinking water for 9 weeks, with 1% of alpha-TP or SAA administered in the diet from 1 week prior to the KBrO(3) treatment until the end of the experiment. Increases in 8-hydroxydeoxyguanosine levels in kidney DNA of both sexes of rats given KBrO(3) were significantly inhibited by SAA, but not alpha-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 alpha-TP. Immunohistochemical and Western blot analyses for alpha(2u)-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 KBrO(3) in both sexes is limited.
Umemura
Takashi
T
Division of Pathology, National Institute of Health Sciences, 1-18-1, Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. umemura@nihs.go.jp
Tasaki
Masako
M
Kijima
Aki
A
Okamura
Toshiya
T
Inoue
Tomoki
T
Ishii
Yuji
Y
Suzuki
Yuta
Y
Masui
Norio
N
Nohmi
Takehiko
T
Nishikawa
Akiyoshi
A
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000510:Alpha-Globulins / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D001959:Bromates / Q000633:toxicity*; D001973:Bromodeoxyuridine / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity*; D049109:Cell Proliferation / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000235:genetics*; D005260:Female; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D016296:Mutagenesis / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects*; D010430:Pentosyltransferases / Q000235:genetics*; D051381:Rats; D011916:Rats, Inbred F344; D055647:Rats, Transgenic; D024502:alpha-Tocopherol / Q000494:pharmacology
D000510:Alpha-Globulins; D000975:Antioxidants; D001959:Bromates; D002273:Carcinogens; D029968:Escherichia coli Proteins; C013803:alpha 2u globulin; C019536:potassium bromate; D000080242:8-Hydroxy-2'-Deoxyguanosine; D010430:Pentosyltransferases; C071962:Gpt protein, E coli; D001973:Bromodeoxyuridine; D003849:Deoxyguanosine; D024502:alpha-Tocopherol; D001205:Ascorbic Acid