CHEMOPREVENTIVE ACTIVITY OF TAMOXIFEN, N-(4-HYDROXYPHENL)RETINAMIDE, AND THE VITAMIN-D ANALOG RO24-5531 FOR ANDROGEN-PROMOTED CARCINOMAS OFTHE RAT SEMINAL-VESICLE AND PROSTATE

We evaluated the ability of dietary N-(4-hydroxyphenyl)retinamide; 1 r oxy-16-ene-23-yne-26,27-hexafluorocholecalciferol (Ro24-5531); and tam oxifen to inhibit the development of androgen-promoted carcinomas of t he accessory sex organs of male Lobund-Wistar rats. Invasive carcinoma s of the seminal vesicle (SV) and anterior prostate (AP) were induced in Lobund-Wistar rats with three different combinations of initiator [ N-nitroso-N-methylurea (NMU)] and promoter [testosterone propionate (T P)]: (a) high-dose NMU (30 mg/kg) + high-dose TP (20 mg via implant ev ery 2 months); (b) high-dose NMU + low-dose TP (10 mg implanted every 2 months); or (c) low-dose NMU (15 mg/kg) + low-dose TP. During the pe riod of TP administration, rats were fed a diet supplemented with eith er N-(4-hydroxyphenyl)retinamide (1 or 2 mmol/kg diet), Ro24-5531 (1.2 5 or 2.5 nmol/kg diet), tamoxifen (0.5 or 5 mg/kg diet), or vehicle al one. After sacrifice at 8.5 or 11 months, the prostate-seminal vesicle complex from each rat was processed in tote and histologically staged as to the extent of tumor involvement. In animals given low-dose TP, an three agents were significantly effective at reducing the incidence of invasive carcinomas of the SV and, to a lesser degree, the AP. Of the three agents, tamoxifen given in high dose (5 mg/kg) had the stron gest activity, reducing the occurrence of invasive SV carcinomas from 72-83% in controls to 6% (P = 0.0001) and the occurrence of invasive A P carcinomas from 50-72% to 18-22% (P < 0.05).