p-Dichlorobenzene (pDCB) is a male rat kidney
carcinogen believed to act through alpha2u-globulin nephropathy. Recent data on metabolism, however, suggest a potential for generating oxidative stress. To examine possible mechanisms of kidney
carcinogenesis, pDCB was studied for ability to produce 8-oxodeoxyguanosine (8-oxodG) in kidney nuclear
DNA and for initiating activity in a two-stage renal
carcinogenesis model. F344 male rats were given pDCB 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 initiation after exposure, trisodium
nitrilotriacetic acid (NTA), a kidney
tumor promoter was given in the
drinking water at 1,000 ppm for 39 weeks. At the 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 not produce oxidative DNA damage in the rat kidney or effect initiation of kidney
carcinogenesis. These data suggest that oxidative stress is not involved in pDCB-induced renal
carcinogenesis. The alpha2u-globulin-mediated chronic nephropathy probably acts as a promoter, not an initiation of renal
carcinogenesis. Accordingly, pDCB is assessed to have no
cancer hazard to humans who are not susceptible to the alpha2u-globulin nephropathy.