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Title:The effect of generational feeding of soy and genistein-supplemented diets on progression of precancerous lesions in colon of second generation male rats
Author(s):Jorud, Ingrid
Advisor(s):Chen, Hong
Department / Program:Food Science & Human Nutrition
Discipline:Food Science & Human Nutrition
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:M.S.
Genre:Thesis
Subject(s):genistein
colon cancer
generational animal model
nutrient-gene interaction
aberrant crypt foci
soy protein isolate
Wnt signaling pathway
Abstract:Colon cancer is the third leading cause of cancer related death in the United States. Epidemiological evidence has shown that populations who consume a traditional East Asian diet high in soy isoflavones have a reduced incidence of developing colon cancer. In previous studies, soy and isoflavones have also been shown to have an effect on reducing colon cancer growth and progression in vitro and in vivo. This study used Sprague Dawley male rats from the second generation of a multiple generation model, which were fed a control, soy, or genistein-supplemented diet. Soy and genistein fed rats had dietary exposure from two previous generations, consumed the same diet and therefore were exposed through gestation, lactation, and post-weaning. Control group rats were obtained at six weeks of age. At ten weeks of age, the rats were injected with azoxymethane (AOM) and were sacrificed at fifteen weeks. Descending colon tissue was collected for physiological, protein, and genetic analysis. Identification of aberrant crypt foci (ACF) was used to determine physiological effect and stage of precancerous progression. Rats fed soy or genistein diets showed significant decrease of total numbers of ACF and reduced multiplicity. Established members of the Wnt signaling pathway, including inhibitors and targets, were analyzed using mRNA expression. Wnt16, Wnt8b, Wnt1, sFRP5, and Dkk1 were significantly increased in the genistein group compared to control and Cyclin D1 was significantly decreased in soy and genistein groups compared to control. β-catenin was used as the protein indicator of Wnt pathway activation. Rats fed a soy or genistein diet showed a significant reduction of nuclear β-catenin. In rats fed soy and genistein diets, advanced stages of ACF decreased, as well as Cyclin D1 expression and nuclear β-catenin also decreased – indicating a reduction in precancerous progression.
Issue Date:2012-05-22
URI:http://hdl.handle.net/2142/30913
Rights Information:Copyright 2012 Ingrid Jorud
Date Available in IDEALS:2012-05-22
Date Deposited:2012-05


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