Document Detail


Null activity of selenium and vitamin e as cancer chemopreventive agents in the rat prostate.
MedLine Citation:
PMID:  20145190     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
David L McCormick; K V N Rao; William D Johnson; Maarten C Bosland; Ronald A Lubet; Vernon E Steele
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-02-09
Journal Detail:
Title:  Cancer prevention research (Philadelphia, Pa.)     Volume:  3     ISSN:  1940-6215     ISO Abbreviation:  Cancer Prev Res (Phila)     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-05     Completed Date:  2010-06-08     Revised Date:  2011-07-25    
Medline Journal Info:
Nlm Unique ID:  101479409     Medline TA:  Cancer Prev Res (Phila)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  381-92     Citation Subset:  IM    
Affiliation:
Life Sciences Research, IIT Research Institute, 10 West 35th Street, Chicago, IL 60616, USA. dmccormick@iitri.org
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MeSH Terms
Descriptor/Qualifier:
Adenocarcinoma / chemically induced,  pathology,  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,  pathology,  prevention & control*
Prostatic Neoplasms / chemically induced,  pathology,  prevention & control*
Rats
Rats, Wistar
Selenium Compounds / therapeutic use*
Selenomethionine / administration & dosage*
Testosterone / administration & dosage
Vitamin E / therapeutic use*
alpha-Tocopherol / therapeutic use
Grant Support
ID/Acronym/Agency:
N01 CN065120/CN/NCI NIH HHS; N01 CN095113/CN/NCI NIH HHS; N01 CN35566-02/CN/NCI NIH HHS; N01-CN-35566-02/CN/NCI NIH HHS; N01-CN-65120/CN/NCI NIH HHS; N01-CN-95113/CN/NCI NIH HHS; P30-CA-16087/CA/NCI NIH HHS; P30-ES-00260/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Alkylating Agents; 0/Androgens; 0/Antioxidants; 0/Selenium Compounds; 1406-18-4/Vitamin E; 1464-42-2/Selenomethionine; 427-51-0/Cyproterone Acetate; 58-22-0/Testosterone; 59-02-9/alpha-Tocopherol; 684-93-5/Methylnitrosourea
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