Potassium Bromate Enhances N-Ethyl-N-Hydroxyethylnitrosamine–Induced Kidney Carcinogenesis Only at High Doses in Wistar Rats: Indication of the Existence of an Enhancement Threshold

Abstract

As susceptibility to carcinogens varies considerably among different strains of experimental animals, evaluation of dose-response relationships for genotoxic carcinogen in different strains is indispensable for risk assessment. Potassium bromate (KBrO(3)) is a genotoxic carcinogen inducing kidney cancers at high doses in male F344 rats, but little is known about its carcinogenic effects in other strains of rats. The purpose of the present study was to determine dose-response relationships for carcinogenic effects of KBrO(3) on N-ethyl-N-hydroxyethylnitrosamine (EHEN)-induced kidney carcinogenesis in male Wistar rats. We found that KBrO(3) showed significant enhancement effects on EHEN-induced kidney carcinogenesis at above 250 ppm but not at doses of 125 ppm and below when evaluated in terms of induction of either preneoplastic lesions or tumors in male Wistar rats. Furthermore, KBrO(3) significantly increased the formation of oxidative DNA damage at doses of 125 and above but not at doses of 30 ppm and below in kidneys. These results demonstrated that low doses of KBrO(3) exert no effects on development of EHEN-initiated kidney lesions and induction of oxidative DNA damage. Taking account of previous similar findings in male F344 rats, it is strongly suggested that a threshold dose exists for enhancement effects of KBrO(3) on kidney carcinogenesis in rats.