Chemoprevention of rat prostate carcinogenesis by early and delayed administration of dehydroepiandrosterone

Two in vivo bioassays were conducted to evaluate the efficacy of dehydroepi androsterone (DHEA) as an inhibitor of prostate carcinogenesis in rats. Pro state adenocarcinomas were induced in male Wistar-Unilever rats by a sequen tial regimen of cyproterone acetate and testosterone propionate, followed b y a single i.v. injection of N-methyl-N-nitrosourea (MNU) and chronic andro gen stimulation. In the first experiment, DHEA (1000 or 2000 mg/kg diet) wa s administered continuously to rats beginning 1 week before MNU exposure, I n the second experiment, continuous administration of DHEA (2000 mg/kg diet ) was begun either I week before, 20 weeks after, or 40 weeks after MNU exp osure. Controls received basal diet without added DHEA, Studies were termin ated at 13 months after MNU administration, and prostate cancer incidence w as determined by histopathological evaluation of step sections of accessory sex glands. In the first study, continuous dietary administration of DHEA beginning 1 week before MNU resulted in a dose-related inhibition of prosta te cancer induction. In the second experiment, comparable reductions in pro state cancer incidence were observed in groups exposed to DHEA beginning 1 week before, 20 weeks after, and 40 weeks after carcinogen exposure, These data demonstrate that nontoxic doses of DHEA confer significant protection against prostate carcinogenesis in rats. The efficacy of delayed administra tion of DHEA suggests that the compound confers protection against later st ages of prostate cancer induction and can suppress the progression of exist ing preneoplastic lesions to invasive disease.