INFLUENCE OF N-METHYL-N-NITROSOUREA, TESTOSTERONE, AND N-(4-HYDROXYPHENYL)-ALL-TRANS-RETINAMIDE ON PROSTATE-CANCER INDUCTION IN WISTAR-UNILEVER RATS

The influence of chemical carcinogen, hormonal stimulation, and chroni c dietary administration of the synthetic retinoid, N-(4-hydroxyphenyl )-all-trans-retinamide (4-HPR), on the induction of prostate cancer in male Wistar-Unilever rats was determined. Three different tumor induc tion regimens were used: (a) a single i.v. dose of 50 mg of N-methyl-N -nitrosourea (MNU) per kg body weight, followed by chronic androgen st imulation via s.c. implantation of two silastic capsules containing 40 mg testosterone each; (b) a single i.v, dose of 50 mg of MNU per kg b ody weight (no testosterone treatment); and (c) chronic androgen stimu lation with implanted testosterone capsules (no MNU treatment). In a f ourth series of animals, the incidence of spontaneous prostate tumors was determined in groups of rats receiving neither carcinogen nor horm one stimulation. Within each series, parallel groups of animals were f ed a control (vehicle-supplemented) diet or control diet supplemented with 4-HPR beginning 1 day after carcinogen administration; retinoid a dministration was continuous until termination of the study at 450 day s. The incidence of accessory sex gland cancer in rats treated sequent ially with MNU + testosterone was >60%, in comparison with cancer inci dences of <20% in rats receiving MNU only and <5% in rats treated with testosterone only. No spontaneous accessory sex gland tumors were obs erved in rats receiving no carcinogen and no testosterone, Tumor induc tion in the accessory sex glands by MNU + testosterone was relatively specific for the prostate: the incidence of carcinoma of the dorsolate ral/anterior prostate was more than 5-fold greater than the incidence of cancer present only in the seminal vesicle. 4-HPR conferred no prot ection against cancer induction in the prostate by any regimen of MNU and/or testosterone, These results demonstrate the importance of both carcinogen exposure and hormone stimulation on the induction of neopla sia in the prostate of Wistar-Unilever rats.