We evaluated the ability of dietary N-(4-hydroxyphenyl)
retinamide; 1 alpha,25-dihydroxy-16-ene-23-yne-26,27-hexafluorocholecalcifero l (Ro24-
5531); and
tamoxifen to inhibit the development of
androgen-promoted
carcinomas of the accessory sex organs of male Lobund-Wistar rats. Invasive
carcinomas 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 (TP)]: (a) high-dose NMU (30 mg/kg) + high-dose TP (20 mg via implant every 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 period of TP administration, rats were fed a diet supplemented with either
N-(4-hydroxyphenyl)retinamide (1 or 2 mmol/kg diet),
Ro24-5531 (1.25 or 2.5 nmol/kg diet),
tamoxifen (0.5 or 5 mg/kg diet), or vehicle alone. After sacrifice at 8.5 or 11 months, the prostate-seminal vesicle complex from each rat was processed in
toto and histologically staged as to the extent of
tumor involvement. In animals given low-dose TP, all 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 strongest activity, reducing the occurrence of invasive SV
carcinomas from 72-83% in controls to 6% (P = 0.0001) and the occurrence of invasive AP
carcinomas from 50-72% to 18-22% (P < 0.05).