Dietary selenium deficiency exacerbates DSS-induced epithelial injury and AOM/DSS-induced tumorigenesis

Autor: Barbara Fingleton, Sean S. Davies, Amber Bradley, Bobak Parang, Elena Matafonova, Vishruth K. Reddy, Kshipra Singh, Raymond F. Burk, Mary K. Lintel, Caitlyn W. Barrett, Rupesh Chaturvedi, Amy K. Motley, Keith T. Wilson, Wei Ning, Kristina E. Hill, Mary Kay Washington, Shenika Poindexter, Christopher S. Williams
Jazyk: angličtina
Rok vydání: 2013
Předmět:
Mouse
Carcinogenesis
Colorectal cancer
lcsh:Medicine
Tumor initiation
medicine.disease_cause
Inflammatory bowel disease
Mice
Oxidative Damage
chemistry.chemical_compound
0302 clinical medicine
Transforming Growth Factor beta
Molecular Cell Biology
Gastrointestinal Cancers
Basic Cancer Research
lcsh:Science
Cellular Stress Responses
0303 health sciences
Multidisciplinary
Cancer Risk Factors
Dextran Sulfate
Animal Models
Colitis
3. Good health
Oncology
8-Hydroxy-2'-Deoxyguanosine
Nutritional Correlates of Cancer
Micronutrient Deficiencies
030220 oncology & carcinogenesis
Colonic Neoplasms
Medicine
medicine.symptom
Signal Transduction
Research Article
Azoxymethane
Inflammation
Gastroenterology and Hepatology
Selenium
03 medical and health sciences
Model Organisms
Weight Loss
medicine
Animals
Neoplastic transformation
Biology
Nutrition
030304 developmental biology
Epidermal Growth Factor
business.industry
Inflammatory Bowel Disease
lcsh:R
Deoxyguanosine
medicine.disease
digestive system diseases
Diet
Mice
Inbred C57BL
Gene Expression Regulation
chemistry
Immunology
lcsh:Q
business
DNA Damage
Zdroj: PLoS ONE, Vol 8, Iss 7, p e67845 (2013)
PLoS ONE
ISSN: 1932-6203
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: