Lack of oxidative DNA damage or initiation of carcinogenesis in the kidneys of male F344 rats given subchronic exposure to p-dichlorobenzene (pDCB)ata carcinogenic dose

p-Dichlorobenzene (pDCB) is a male rat kidney carcinogen believed to act th rough alpha(2u)-globulin nephropathy. Recent data on metabolism, however, s uggest a potential for generating oxidative stress. To examine possible mec hanisms of kidney carcinogenesis, pDCB was studied for ability to produce 8 -oxodeoxyguanosine (8-oxodG) in kidney nuclear DNA and for initiating activ ity in a two-stage renal carcinogenesis model. F344 male rats were given pD CB by intragastric instillation, 5 days/week for 13 weeks at 300 mg/kg per day, which is a carcinogenic dose with chronic administration. To assess in itiation after exposure, trisodium nitrilotriacetic acid (NTA), a kidney tu mor promoter was given in the drinking water at 1000 ppm for 39 weeks. At t he end of the exposure segment, pDCB did not produce an increase of 8-oxodG levels in the kidney nuclear DNA in contrast to potassium bromate (KBrO3). Following NTA promotion, no neoplastic lesions occurred in rats given pDCB , although diethylnitrosamine carcinogenesis was enhanced. Thus, pDCB did n ot produce oxidative DNA damage in the rat kidney or effect initiation of k idney carcinogenesis. These data suggest that oxidative stress is not invol ved in pDCB-induced renal carcinogenesis. The alpha(2u)-globulin-mediated c hronic nephropathy probably acts as a promoter, not an initiation of renal carcinogenesis. Accordingly, pDCB is assessed to have no cancer hazard to h umans who are not susceptible to the alpha(2u)-globulin nephropathy.