title: 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.
authors.affiliation: Department of Pathology, Osaka City University Medical School, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
authors.forename: Min
authors.initials: M
authors.lastname: Wei
authors.forename: Al-Salmy
authors.initials: AS
authors.lastname: Hamoud
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Anna
authors.initials: A
authors.lastname: Kakehashi
authors.forename: Keiichirou
authors.initials: K
authors.lastname: Morimura
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Doi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Kushida
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Kitano
authors.forename: Hideki
authors.initials: H
authors.lastname: Wanibuchi
authors.forename: Shoji
authors.initials: S
authors.lastname: Fukushima
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001959:Bromates / Q000737:chemistry / Q000633:toxicity*; D002273:Carcinogens / Q000737:chemistry / Q000633:toxicity*; D004249:DNA Damage / Q000187:drug effects; D004260:DNA Repair / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004052:Diethylnitrosamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007680:Kidney Neoplasms / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001959:Bromates; D002273:Carcinogens; D012333:RNA, Messenger; C019536:potassium bromate; C023845:N-ethyl-N-hydroxyethylnitrosamine; D004052:Diethylnitrosamine; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine