Sequential changes in the prostate of rats treated with chlormadinone acetate, testosterone and N-nitroso-N-methylurea.

An attempt was made to induce prostatic adenocarcinoma in rats. Temporary chemical castration of F344 rats was achieved by administration of diet containing 0.05% chlormadinone acetate (CMA) for three weeks. The prostate was then stimulated by three consecutive daily intramuscular injections of testosterone propionate (100 mg./kg.). On the day after the last testosterone injection, N-nitroso-N-methylurea (NMU) (50 mg./kg.) was injected intravenously. Animals were sacrificed 10 days and 4, 20, 40 and 60 weeks after NMU treatment. Well-differentiated adenocarcinomas were obtained in three of fifty-four animals (5.6%) by this treatment and a high incidence of simple hyperplasia (88%) and atypical hyperplasia (19%) was also observed at 60 weeks. More studies are necessary to develop a protocol resulting in more rapid induction of prostatic adenocarcinomas at higher incidence.