Promoting effects of antiandrogenic agents on rat ventral prostate carcinogenesis induced by 3,2 '-dimethyl-4-aminobiphenyl (DMAB)

The objective of this study was to determine the effects of androgen deplet ion by 5 alpha-reductase inhibitor (eg epristeride), pure antiandrogen (eg casodex) or C17-20 lyase inhibitor (eg YM116) on rat prostate carcinogenesi s induced by administration of 3,2'-dimethyl-4-aminobiphenyl (DMAB). DMAB was subcutaneously administered on male F344 rats for the first 20 wee ks. Epristeride (10 and 50 mg/kg, three times per week), casodex (15 and 30 mg/kg, three times per week) or YM116 (15 and 30 mg/kg, three times per we ek) were administered orally for 40 consecutive weeks. Then, all accessory sex organs were studied for the formation of neoplastic lesions by histolog ical examination. All carcinoma lesions were produced only in the ventral lobe of the prostat e. The incidence of carcinoma developing in the ventral lobe of the prostat e was 9.5% in the control group on which DMAB alone was administered, where as it was 31.6% in the epristeride 10 mg/kg group. 45.0% in the epristeride 50 mg/kg group, 47.8% in the casodex 15 mg/kg group, 63.2% in the casodex 30 mg/kg group, 10.5% in the YM116 15 mg/kg group and 5.0% in the YM116 30 mg/kg group. The incidences of carcinoma in the epristeride 10 mg/kg group, casodex 15 mg/kg group and casodex 30 mg/kg group were significantly highe r than that of the control group. In this experimental model, all ventral p rostate carcinomas were in situ adenocarcinomas that did not form palpable nodules or distant metastasis. Epristeride and casodex showed a dose-dependent promoting effect on rat ven tral prostate carcinogenesis. These results were contradictory to the resul ts of our previous studies; exogenous testosterone in combination with DMAB produced palpable, and metastatic tumors in other portions of accessory se x organs of F344 rats but no carcinoma in ventral prostate, and those invas ive carcinomas were significantly inhibited by 5 alpha-reductase inhibitor and nonsteroidal antiandrogen. The action mechanisms of androgen and the ef fects of androgen-regulatory drugs on prostate carcinogenesis should be fur ther studied.