A possible role for oxidative stress in potassium bromate (KBrO3) carcinogenesis.
In order to clarify the role of oxidative stress in carcinogenesis by potassium bromate (KBrO3), 8-hydroxydeoxyguanosine (8-OH-dG) levels and cumulating replicating fractions (CRFs) were measured in the kidneys and livers of F344 rats receiving gavage doses of 100, 200 or 400 mg/kg. We used female rats in this study to allow the potential of KBrO3 for inducing alpha 2u-globulin accumulation--known to result in sustained cell proliferation and eventual promoting activity in males--to be ignored. Additional female rats were given 0.05% N-ethyl-N-hydroxyethylnitrosamine (EHEN) orally for the first 2 weeks as an initiator with subsequent administration of KBrO3 at a dose of 500 p.p.m. in the drinking water for 30 weeks. 8-OH-dG levels in the kidneys were significantly elevated with doses of 200 and 400 mg/kg, and this correlated with increases of the CRFs of proximal tubules. In the livers, however, no significant changes were found. In the promotion bioassay, the mean numbers of atypical tubules, atypical hyperplasias and renal cell tumors per rat in animals treated with KBrO3 after EHEN initiation were significantly higher than those in animals receiving distilled water after EHEN initiation. In contrast, there were no significant differences between groups in terms of liver tumors. The overall data suggest that oxidative stress generated by KBrO3 exposure might be associated with induction of cell proliferation and associated promoting activity.
Umemura
T
T
Division of Toxicology, Biological Safety Research Center, National Institute of Health Sciences, Tokyo, Japan.
Sai
K
K
Takagi
A
A
Hasegawa
R
R
Kurokawa
Y
Y
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001959:Bromates / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D004247:DNA / Q000032:analysis; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D005260:Female; D007680:Kidney Neoplasms / Q000139:chemically induced*; D007684:Kidney Tubules / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced*; D018384:Oxidative Stress; D051381:Rats; D011916:Rats, Inbred F344
D001959:Bromates; D002273:Carcinogens; C019536:potassium bromate; D000080242:8-Hydroxy-2'-Deoxyguanosine; D004247:DNA; D003849:Deoxyguanosine