Chemopreventive activity of tamoxifen, N- (4-hydroxyphenyl) retinamide, and the vitamin D analogue Ro24-5531 for androgen-promoted carcinomas of the rat seminal vesicle and prostate
Lucia, M.S.; Anzano, M.A.; Slayter, M.V.; Anver, M.R.; Green, D.M.; Shrader, M.W.; Logsdon, D.L.; Driver, C.L.; Brown, C.C.; Peer, C.W.
Cancer Research 55(23): 5621-5627
1995
ISSN/ISBN: 0008-5472 PMID: 7585644 Document Number: 441401
The ability of dietary N-(4-hydroxyphenyl)retinamide; 1 alpha ,25-dihydroxy-16-ene-23-yne-26,27-hexafluorochlolecalciferol (Ro24-5531) and tamoxifen to inhibit the development of androgen-promoted carcinomas of the accessory sex organs of male Lobund-Wistar rats was investigated. Invasive carcinomas of the seminal vesicle (SV) and anterior prostate (AP) were induced in Lobund-Wistar rats with 3 combinations of initiator (N-nitroso-N-methylurea (NMU)) and promoter (testosterone propionate (TP)): high-dose NMU (30 mg/kg + high-dose TP (20 mg via implant every 2 months)); high-dose NMU + low-dose TP (10 mg implanted every 2 months); or low-dose NMU (15 mg/kg) + low-dose TP. During the period of TP administration, rats were fed on a diet supplemented with N-(4-hydroxyphenyl)retinamide (1 or 2 nmol/kg diet), Ro24-5531 (1.25 or 2.5 nmol/kg diet), tamoxifen (0.5 or 5 mg/kg diet) or vehicle alone. After killing 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 tumour involvement. In rats given low-dose TP, all 3 agents were significantly effective at reducing the incidence of invasive carcinomas of the SV and, to a lesser degree, the AP. Of the 3 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).