Title: Null activity of selenium and vitamin e as cancer chemopreventive agents in the rat prostate.
Authors: McCormick, David L; Rao, K V N; Johnson, William D; Bosland, Maarten C; Lubet, Ronald A; Steele, Vernon E
Published In Cancer Prev Res (Phila), (2010 Mar)
Abstract: To evaluate the potential efficacy of selenium and vitamin E as inhibitors of prostate carcinogenesis, four chemoprevention studies using a common protocol were done in a rat model of androgen-dependent prostate cancer. After stimulation of prostate epithelial cell proliferation by a sequential regimen of cyproterone acetate followed by testosterone propionate, male Wistar-Unilever rats received a single i.v. injection of N-methyl-N-nitrosourea (MNU) followed by chronic androgen stimulation via subcutaneous implantation of testosterone pellets. At 1 week post-MNU, groups of carcinogen-treated rats (39-44/group) were fed either a basal diet or a basal diet supplemented with l-selenomethionine (3 or 1.5 mg/kg diet; study 1), dl-alpha-tocopherol (vitamin E, 4,000 or 2,000 mg/kg diet; study 2), l-selenomethionine + vitamin E (3 + 2,000 mg/kg diet or 3 + 500 mg/kg diet; study 3), or selenized yeast (target selenium levels of 9 or 3 mg/kg diet; study 4). Each chemoprevention study was terminated at 13 months post-MNU, and prostate cancer incidence was determined by histopathologic evaluation. No statistically significant reductions in prostate cancer incidence were identified in any group receiving dietary supplementation with selenium and/or vitamin E. These data do not support the hypotheses that selenium and vitamin E are potent cancer chemopreventive agents in the prostate, and when considered with the recent clinical data reported in the Selenium and Vitamin E Cancer Prevention Trial (SELECT), show the predictive nature of this animal model for human prostate cancer chemoprevention.
PubMed ID: 20145190
MeSH Terms: Adenocarcinoma/chemically induced; Adenocarcinoma/pathology; Adenocarcinoma/prevention & control*; Alkylating Agents/toxicity; Androgens/administration & dosage; Animals; Antioxidants/pharmacology; Cyproterone Acetate/therapeutic use; Disease Models, Animal; Drug Therapy, Combination; Male; Methylnitrosourea/toxicity; Neoplasms, Hormone-Dependent/chemically induced; Neoplasms, Hormone-Dependent/pathology; Neoplasms, Hormone-Dependent/prevention & control*; Prostatic Neoplasms/chemically induced; Prostatic Neoplasms/pathology; Prostatic Neoplasms/prevention & control*; Rats; Rats, Wistar; Selenium Compounds/therapeutic use*; Selenomethionine/administration & dosage*; Testosterone/administration & dosage; Vitamin E/therapeutic use*; alpha-Tocopherol/therapeutic use