Duration dependent induction of invasive prostatic carcinomas with pharmacological dose of testosterone propionate in rats pretreated with 3,2'-dimethyl-4-aminobiphenyl and development of androgen-independent carcinomas after castration.

Male F344 rats were first treated with 3,2'-dimethyl-4-aminobiphenyl for 20 weeks in the presence of testicular androgens and then administered of a pharmacological dose of testosterone propionate (TP) for various periods (maximum 40 weeks). This resulted in development of invasive carcinomas in the dorso-lateral prostate as well as the seminal vesicles whose incidences were TP duration-dependent. However, in situ carcinomas of the ventral prostate were not affected by the TP treatment and atypical hyperplasias were clearly decreased. When animals were subjected to orchiectomy after 20-weeks-treatment with the TP, invasive adenocarcinomas were still subsequently noted in the dorso-lateral prostate and seminal vesicles, demonstrating a certain androgen-independence. The data indicate that, in spite of the necessity of high dose of TP for induction of invasive prostate carcinomas in the present experimental model, a proportion of the resulting tumors are hormone-independent.