Null activity of selenium and vitamin e as cancer chemopreventive agents in the rat prostate.

Null activity of selenium and vitamin e as cancer chemopreventive agents in the rat prostate.
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DOI:
10.1158/1940-6207.capr-09-0176
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发表时间:
2010-03
期刊:
Cancer prevention research (Philadelphia, Pa.)
影响因子:
--
通讯作者:
Steele VE
Steele VE
中科院分区:
其他
文献类型:
--
作者:
McCormick DL;Rao KV;Johnson WD;Bosland MC;Lubet RA;Steele VE

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To evaluate the potential efficacy of selenium and vitamin E as inhibitors of prostate carcinogenesis, four chemoprevention studies using a common protocol were performed 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 intravenous injection of N-methyl-N-nitrosourea (MNU) followed by chronic androgen stimulation via subcutaneous implantation of testosterone pellets. At one week post-MNU, groups of carcinogen-treated rats (39–44/group) were fed either basal diet or basal diet supplemented with L-selenomethionine (3 or 1.5 mg/kg diet; Study 1); DL-α-tocopherol (Vitamin E; 4000 or 2000 mg/kg diet; Study 2); L-selenomethionine + Vitamin E (3 + 2000 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 SELECT trial, demonstrate the predictive nature of this animal model for human prostate cancer chemoprevention.