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Please use this identifier to cite or link to this item: http://hdl.handle.net/123456789/17119

Authors: O A Michael R. Franklin1, , , , and Jeanette C. Roberts2
Philip J. Moos1
Wael M. El-Sayed1
Tarek Aboul-Fadl1
Keywords: Lung Cancer; Cancer chemoprevention; Selenium; Selenazolidine; Tobacco derived nitrosamine
Issue Date: 2007
Publisher: Chem Biol Interact.
Abstract: The efficacy of a series of 2-aryl/alkyl selenazolidine-4(R)-carboxylic acids (SCAs) in reducing NNK [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone]-induced lung adenomas in female AJ mice, a model for tobacco-related lung tumorigenesis, has been investigated. With selenazolidines in the diet for one month prior to carcinogen administration and during the subsequent four months of tumor development, 2-butylSCA, 2-cyclohexylSCA, 2-phenylSCA and 2-oxoSCA were chemopreventive, significantly reducing mean lung tumor numbers from the 10.9 of unsupplemented controls to 4.7, 5.3, 2.8 and 4.7 respectively. When elenazolidine supplementation began three days after carcinogen administration (i.e., post-initiation), 2-butylSCA, 2-cyclohexylSCA, and 2-oxoSCA were chemopreventive. In both regimens, selenocystine was also chemopreventive. In the post-initiation protocol, but with intervention at a precancerous stage (thirteen days), whole genome expression analysis of lung RNA identified six gene transcripts that weakly correlated with the efficacy of tumor reduction by the four selenocompounds at four months. None of these genes were among those identified as influenced by chemopreventive selenium compounds in human lung cancer cell lines. When supplementation was for one month-prior until 3 days-after carcinogen administration, 2- butylSCA, and 2-phenylSCA were chemopreventive but selenocystine was ineffective. Both 2-butylSCA and 2-phenylSCA retained their chemopreventive activity (44% and 40% tumor number reduction respectively), when the supplementation was shortened and restricted to a pre-initiation period (days -9 to -2). With supplementation spanning 2 days-prior until 3 days-after NNK, reductions in tumor numbers by 2-phenylSCA (26%) and 2-butylSCA (17%) did not achieve statistical significance. Thus, several 2-aryl/alkyl selenazolidines possess chemopreventive activity against NNK-induced lung tumors, and variously demonstrate pre-initiation and post-initiation efficacy.
URI: http://hdl.handle.net/123456789/17119
Appears in Collections:College of Pharmacy

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