Sequential changes in the prostate of rats treated with chlormadinone acetate, testosterone and...

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.