Null activity of selenium and vitamin e as cancer chemopreventive agents in the rat prostate.
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.
McCormick
David L
DL
Life Sciences Research, IIT Research Institute, 10 West 35th Street, Chicago, IL 60616, USA. dmccormick@iitri.org
Rao
K V N
KV
Johnson
William D
WD
Bosland
Maarten C
MC
Lubet
Ronald A
RA
Steele
Vernon E
VE
D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D000477:Alkylating Agents / Q000633:toxicity; D000728:Androgens / Q000008:administration & dosage; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017373:Cyproterone Acetate / Q000627:therapeutic use; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D008297:Male; D008770:Methylnitrosourea / Q000633:toxicity; D009376:Neoplasms, Hormone-Dependent / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D011471:Prostatic Neoplasms / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D018036:Selenium Compounds / Q000627:therapeutic use*; D012645:Selenomethionine / Q000008:administration & dosage*; D013739:Testosterone / Q000008:administration & dosage; D014810:Vitamin E / Q000627:therapeutic use*; D024502:alpha-Tocopherol / Q000627:therapeutic use
D000477:Alkylating Agents; D000728:Androgens; D000975:Antioxidants; D018036:Selenium Compounds; D014810:Vitamin E; D013739:Testosterone; D017373:Cyproterone Acetate; D008770:Methylnitrosourea; D012645:Selenomethionine; D024502:alpha-Tocopherol