Vitamin C reduces the Incidence and severity of renal tumors induced by estradiol or diethylstilbestrol

Abstract

The chronic administration of estradiol or di-ethylstilbestrol to male Syrian hamsters induces kidney tumors. The effect of vitamin C treatment on estrogen-induced carcinogenesis has been studied to elucidate the mechanism of tumor induction by estrogen. Vitamin C decreases the tumor incidence by ∼50% but does not influence hormone-dependent growth of kidney tumors. Moreover, vitamin C lowers the concentration of diethylstilbestrol-4′,4″-quinone, the genotoxic metabolite of diethylstilbestrol, in vitro and in Syrian hamsters treated with stilbene. Vitamin C also decreases the levels in hamsters of di-ethylstilbestrol-DNA adducts formed by the quinone metabolite. Estrogens may thus initiate tumors by their metabolic oxidation to corresponding quinone metabolites, which bind covalently to cellular macromolecules. Vitamin C may inhibit tumorigen-esis by decreasing concentrations of quinone metabolites and their DNA adducts. Lowering quinone metabolite concentrations may also inhibit free radical generation by decreasing redox cycling between estrogens and their corresponding quinones.