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Diet Induced Obesity Increases the Risk of Colonic Tumorigenesis in Mice
Authors:Angelos K Sikalidis  Mark D Fitch  Sharon E Fleming
Institution:1. Department of Nutritional Sciences and Toxicology, University of California, Berkeley, CA, 94720, USA
2. Harvard Institutes of Medicine, Dana-Farber Cancer Institute, 77 Avenue Louis Pasteur, Boston, MA, 02115, USA
Abstract:A large body of epidemiological data indicates that obesity increases the risk of colon cancer in humans. There are limited studies using rodent models where the relationship between obesity and colon cancer has been studied. In this study, wild-type diet-induced obese (DIO) mice and lean wild-type controls were used to investigate the influence of obesity on the risk of colon cancer. We hypothesized that the obese phenotype would exhibit increased colonic tumorigenesis. Colon cancer was chemically induced by injecting the mice with azoxymethane (AOM) at levels that we experimentally determined to result in equivalent AOM concentrations in circulating blood. Risk of colon cancer was assessed via microscopic examination of entire colons for aberrant crypts, aberrant crypt foci and proliferation levels. The DIO mice were found to have significantly more aberrant crypts and aberrant crypt foci as well as increased proliferation of colonocytes per mouse compared to wild-type control mice, supporting the epidemiological data that obesity increases the risk of colonic tumorigenesis.
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