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.
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).
Lucia
M S
MS
Laboratory of Chemoprevention, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Anzano
M A
MA
Slayter
M V
MV
Anver
M R
MR
Green
D M
DM
Shrader
M W
MW
Logsdon
D L
DL
Driver
C L
CL
Brown
C C
CC
Peer
C W
CW
D000728:Androgens; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002273:Carcinogens; D004354:Drug Screening Assays, Antitumor; D008297:Male; D008770:Methylnitrosourea; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D009376:Neoplasms, Hormone-Dependent / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D011467:Prostate / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D012669:Seminal Vesicles / Q000187:drug effects / Q000473:pathology; D013629:Tamoxifen / Q000627:therapeutic use*; D013739:Testosterone
D000728:Androgens; D016588:Anticarcinogenic Agents; D002273:Carcinogens; C086492:Ro 24-5531; D013629:Tamoxifen; D013739:Testosterone; D008770:Methylnitrosourea; D002117:Calcitriol