Coadministration of vitamin C to estrogen-treated Syrian hamsters significantly lowered the incidence of estradiol-induced renal carcinoma. The aim of the proposed study is the elucidation of the mechanism of action of vitamin C in this tumor model. The knowledge of how vitamin C inhibits estrogen-induced carcinogenesis will benefit in two ways: 1. It will aid in understanding the mechanism of tumorigenesis by estrogens. 2. The use of vitamin C to inhibit tumor formation may have a more general preventative value in other tumors as well. It is suspected that vitamin C administration to estrogen-treated Syrian hamsters in some unknown way influences estrogen metabolism and thus prevents cellular damage by reactive estrogen metabolites. This hypothesis will be tested in the following way: 1. Estradiol metabolic profiles of chronically estradiol-treated Syrian hamsters with or without coadministration of vitamin C will be examined. Metabolite profiles will be examined for any evidence of reduction of quinone/semiquinone metabolites by vitamin C. 2. The influence of vitamin C treatment in vivo on estradiol-induced DNA adduct profiles will be studied. 3. The influence of vitamin C treatment in vivo on repair of estrogen-induced DNA adducts will be investigated. 4. The activity of estradiol 2/4 hydroxylase in estrogen-treated hamsters under influence of vitamin C will be tested. 5. The influence of vitamin C treatment on prostaglandin endoperoxide synthase in hamster kidney will be studied. 6. Activity levels of superoxide dismutase and also glutathione transferase will be measured in estrogen-treated animals with or without coadministration of vitamin C.