Lack of chemopreventive activity of lycopene in the Wistar-Unilever rat prostate cancer model

3906 Several epidemiology studies have identified an inverse association between consumption of tomato-based products and prostate cancer risk. Although this relationship has not been a universal finding, the possible activity of lycopene and/or other tomato components as inhibitors of prostate carcinogenesis remains a compelling hypothesis. The present study was conducted to evaluate the hypothesis that consumption of lycopene protects against prostate cancer induction in rats. A preliminary diet tolerance study identified no clinical evidence of toxicity when lycopene was administered at levels of up to 5000 mg/kg diet. In blood samples collected after six weeks of exposure, plasma lycopene demonstrated a linear increase with dose between 0 and 5000 mg/kg diet. Based on a multiple of presumed human exposure, lycopene doses of 500 and 2500 mg/kg diet were selected for use in the prostate cancer chemoprevention study. In the chemoprevention study, hormone-dependent prostate cancers were induced in male Wistar-Unilever rats by a sequential regimen of antiandrogen –androgen –chemical carcinogen –androgen. Rats were treated with cyproterone acetate (50 mg/kg/day for 21 days via gavage) followed by testosterone propionate (100 mg/kg/day for 3 days via subcutaneous injection). Sixty hours after the first dose of testosterone propionate, rats (40 to 42 per group) rats received a single intravenous injection of N -methyl- N -nitrosourea [MNU; 30 mg/kg body weight]. Beginning one week post-MNU, chronic androgen stimulation was provided by 2 subcutaneous pellets containing 40 mg of crystalline testosterone; pellets were replaced at intervals of 6 months. Dietary administration of lycopene was initiated one week post-MNU, and was continued until the termination of the study at 13 months. Accessory sex glands were collected from all study animals at necropsy, and cancer incidence was determined by histopathologic evaluation of interrupted step sections prepared from all glands. Dietary administration of lycopene conferred no protection against prostate carcinogenesis in this study. In comparison to a total cancer incidence of 63% (all accessory sex glands) in dietary controls, total cancer incidences of 81% and 69% were observed in groups fed the low and high doses of lycopene. Similarly, cancers that were clearly limited to the dorsolateral/anterior prostate were found in 48% of dietary controls versus 60% and 43% of rats in groups fed the low and high doses of lycopene, respectively. None of these differences was significant at the 5% level of confidence. Cancer incidence in the seminal vesicle was less than 15% in all groups. These data do not support the hypothesis that lycopene is a potent inhibitor of prostate carcinogenesis. (Supported by NO1-CN-95113 from the NCI.)