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.
Life Sciences Research, IIT Research Institute, 10 West 35th Street, Chicago, IL 60616, USA. dmccormick@iitri.org
David L
DL
McCormick
K V N
KV
Rao
William D
WD
Johnson
Maarten C
MC
Bosland
Ronald A
RA
Lubet
Vernon E
VE
Steele
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