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-hydroxydeoxy-guanosine (8-OH-dG) levels a nd cumulating replicating fractions (CRFs) were measured in the kidney s 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 susta ined cell proliferation and eventual promoting activity in males-to be ignored, Additional female rats were given 0.05% N-ethyl-N-hydroxyeth ylnitrosamine (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 dri nking water for 30 weeks. 8-OH-dG levels in the kidneys were significa ntly elevated with doses of 200 and 400 mg/kg, and this correlated wit h increases of the CRFs of proximal tubules, In the livers, however, n o significant changes were found, In the promotion bioassay, the mean numbers of atypical tubules, atypical hyperplasias and renal cell tumo rs per rat in animals treated with KBrO3 after EHEN initiation were si gnificantly higher than those in animals receiving distilled water aft er EHEN initiation, In contrast, there were no significant differences between groups in terms of liver tumors. The overall data suggest tha t oxidative stress generated by KBrO3 exposure might be associated wit h induction of cell proliferation and associated promoting activity.