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Modeling Colitis-Associated Cancer with Azoxymethane (AOM) and Dextran Sulfate Sodium (DSS)
Published on: September 11, 2012
Microarray Analyses of Genes Differentially Expressed by Diet (Black Beans and Soy Flour) during Azoxymethane-Induced
Elizabeth A Rondini1, Maurice R Bennink
1Department of Food Science and Human Nutrition, 106 GM Trout Building, Michigan State University, East Lansing, MI 48824, USA.
Abstract:
We previously demonstrated that black bean (BB) and soy flour (SF)-based diets inhibit azoxymethane (AOM)-induced colon cancer. The objective of this study was to identify genes altered by carcinogen treatment in normal-appearing colonic mucosa and those attenuated by bean feeding. Ninety-five male F344 rats were fed control (AIN) diets upon arrival. At 4 and 5 weeks, rats were injected with AOM (15 mg/kg) or saline and one week later administered an AIN, BB-, or SF-based diet. Rats were sacrificed after 31 weeks, and microarrays were conducted on RNA isolated from the distal colonic mucosa. AOM treatment induced a number of genes involved in immunity, including several MHC II-associated antigens and innate defense genes (RatNP-3, Lyz2, Pla2g2a). BB- and SF-fed rats exhibited a higher expression of genes involved in energy metabolism and water and sodium absorption and lower expression of innate (RatNP-3, Pla2g2a, Tlr4, Dmbt1) and cell cycle-associated (Cdc2, Ccnb1, Top2a) genes. Genes involved in the extracellular matrix (Col1a1, Fn1) and innate immunity (RatNP-3, Pla2g2a) were induced by AOM in all diets, but to a lower extent in bean-fed animals. This profile suggests beans inhibit colon carcinogenesis by modulating cellular kinetics and reducing inflammation, potentially by preserving mucosal barrier function.
Insights
Black bean and soy flour diets inhibit colon cancer by modulating gene expression. These diets reduce inflammation and cell proliferation, suggesting a protective effect against carcinogen-induced tumors.
Area of Science:
- Nutritional Science
- Gastroenterology
- Molecular Biology
Background:
- Previous studies showed black bean (BB) and soy flour (SF) diets inhibit azoxymethane (AOM)-induced colon cancer.
- Understanding the molecular mechanisms underlying this inhibition is crucial for cancer prevention strategies.
Purpose of the Study:
- To identify genes altered by AOM treatment in colonic mucosa.
- To determine how BB and SF diets attenuate these AOM-induced changes.
Main Methods:
- Ninety-five male F344 rats were fed control, BB-, or SF-based diets after AOM or saline injection.
- Gene expression profiling was performed on colonic mucosa using microarrays after 31 weeks.
Main Results:
- AOM treatment upregulated genes related to immunity and extracellular matrix.
- BB and SF diets downregulated innate immunity and cell cycle genes.
- Bean-based diets showed lower induction of extracellular matrix and innate immunity genes by AOM.
Conclusions:
- Black beans and soy flour inhibit colon carcinogenesis by modulating cellular kinetics and reducing inflammation.
- Bean consumption may preserve mucosal barrier function, contributing to cancer prevention.
