DIETARY FENRETINIDE, A SYNTHETIC RETINOID, DECREASES THE TUMOR-INCIDENCE AND THE TUMOR MASS OF RAS-INDUCED CARCINOMAS IN THE MOUSE PROSTATERECONSTITUTION MODEL SYSTEM(MYC)

Several epidemiological studies have implicated low dietary and serum levels of retinol with an increased risk for the development of human prostate cancer. In a recent report, dietary fenretinide [N-[(4-hydrox yphenyl)] retinamide], a synthetic retinoid with low toxicity, decreas ed the incidence of experimentally induced prostate cancer. Fenretinid e is currently being evaluated in phase I and phase II clinical trials as an agent for both the treatment and chemoprevention of human prost ate cancer. Because of these findings, we investigated whether dietary fenretinide could alter the incidence or phenotype of oncogene-induce d prostate cancer in the mouse prostate reconstitution model system. W hen compared to control-fed animals, dietary fenretinide reduced the t umor incidence by 49% and the tumor mass by 52% of ras+myc-induced can cers in the mouse prostate reconstitution model system, which was modi fied to prolong the latency period before cancer development. Retinoid s have a wide ranging effect on cellular differentiation, growth facto r synthesis, and immune function. While its mechanism of action in thi s system remains unclear, fenretinide is an effective agent for the ch emoprevention and growth modulation of oncogene-induced prostate cance r in the mouse prostate reconstitution model system and may be effecti ve for the, chemoprevention of human prostate cancer.