Open AccessDose‐related changes of oxidative stress and cell proliferation in kidneys of male and female F344 rats exposed to potassium bromate
Author(s) -
Umemura Takashi,
Kitamura Yasuki,
Kanki Keita,
Maruyama Satoshi,
Okazaki Kazushi,
Imazawa Takayoshi,
Nishimura Tetsuji,
Hasegawa Ryuichi,
Nishikawa Akiyoshi,
Hirose Masao
Publication year - 2004
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2004.tb03221.x
Subject(s) - tbars , potassium bromate , oxidative stress , chemistry , lipid peroxidation , thiobarbituric acid , carcinogen , endocrinology , medicine , kidney , toxicology , biochemistry , biology , catalysis
It is still of importance to investigate renal carcinogenesis by potassium bromate (KBrO 3 ), a by‐product of water disinfection by ozonation, for assessment of the risk to man. Five female F344 rats in each group were given KBrO 3 at a dose of 300 mg/kg by single i.g. intubation or at a dose of 80 mg/kg by single i.p. injection, and were killed 48 h after the administration for measurements of thiobarbituric acid‐reactive substances (TBARS) and 8‐oxodeoxyguanosine (8‐oxodG) levels in the kidney. Both levels in the treated animals were significantly elevated as compared with the control values. In a second experiment, 5 male and female F344 rats in each group were administered KBrO 3 at concentrations of 0, 15, 30, 60, 125, 250 and 500 ppm in the drinking water for 4 weeks. KBrO 3 in the drinking water did not elevate TBARS in either sex at any of the doses examined, but 8‐oxodG formation in both sexes at 250 ppm and above was significantly higher than in the controls. Additionally, the bromodeoxyuridine‐labeling index for proximal convoluted tubules was significantly increased at 30 ppm and above in the males, and at 250 ppm and above in the females. α2u‐Globulin accumulation in the kidneys of male rats was increased with statistical significance at 125 ppm and above. These findings suggest that DNA oxidation induced by KBrO 3 may occur independently of lipid peroxidation and more than 250 ppm KBrO 3 in the drinking water can exert a carcinogenic effect by way of oxidative stress.