Dietary Selenium Deficiency Exacerbates DSS-Induced Epithelial Injury and AOM/DSS-Induced Tumorigenesis
Year: 2013
Type: article
Abstract: Selenium (Se) is an essential micronutrient that exerts its functions via selenoproteins. Little is known about the role of Se in inflammatory bowel disease (IBD). Epidemiological studies have inversely correlated nutritional Se status with IBD severity and colon cancer risk. Moreover, molecular studies have revealed that Se deficiency activates WNT signaling, a pathway essential to intestinal stem cell programs and pivotal to injury recovery processes in IBD that is also activated in inflammatory neoplastic transformation. In order to better understand the role of Se in epithelial injury and tumorigenesis resulting from inflammatory stimuli, we examined colonic phenotypes in Se-deficient or -sufficient mice in response to dextran sodium sulfate (DSS)-induced colitis, and azoxymethane (AOM) followed by cyclical administration of DSS, respectively. In response to DSS alone, Se-deficient mice demonstrated increased morbidity, weight loss, stool scores, and colonic injury with a concomitant increase in DNA damage and increases in inflammation-related cytokines. As there was an increase in DNA damage as well as expression of several EGF and TGF-β pathway genes in response to inflammatory injury, we sought to determine if tumorigenesis was altered in the setting of inflammatory carcinogenesis. Se-deficient mice subjected to AOM/DSS treatment to model colitis-associated cancer (CAC) had increased tumor number, though not size, as well as increased incidence of high grade dysplasia. This increase in tumor initiation was likely due to a general increase in colonic DNA damage, as increased 8-OHdG staining was seen in Se-deficient tumors and adjacent, non-tumor mucosa. Taken together, our results indicate that Se deficiency worsens experimental colitis and promotes tumor development and progression in inflammatory carcinogenesis.
Source: PLoS ONE
Authors: Caitlyn W. Barrett, Kshipra Singh, Amy K. Motley, Mary K. Lintel, Elena Matafonova, Amber M. Bradley, Wei Ning, Shenika V. Poindexter, Bobak Parang, Vishruth K. Reddy, Rupesh Chaturvedi, Barbara M. Fingleton, Mary K. Washington, Keith T. Wilson, Sean S. Davies, Kristina E. Hill, Raymond F. Burk, Christopher S. Williams
Language: English
Subfield: Nutrition and Dietetics
Field: Nursing
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,382
Funders: U.S. Department of Veterans Affairs, Vanderbilt University, National Institutes of Health, Vanderbilt Digestive Diseases Research Center, Vanderbilt University Medical Center, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Complementary and Integrative Health
Awards: G1046522931, G12621515, The role of MTGR1 in intestinal biology and inflammation, G165687094, G1788375732, G1806196891, G2068463214, G2268269956, G2523599096, G256475304, G3007470758, Medical Scientist Training Program, G4220223662, G4308745201, G4321410071, G4694584828, The Role of BVES in Intestinal Repair Programs and Inflammatory Bowel Disease, SPORE in GI Cancer, G48435065, Initiative for Maximizing Student Development, G6678749481, G721623835, G725763919, G7642566612, G7931416476, G8734882506, G9000018122, G9000023350, G9000040438, G9000064184, G9000076948, G9000109563, G9000311349, Molecular and Cellular Basis for Digestive Diseases, G932275120
OpenAlex ID: W2007445491