IMPACT OF CALCIUM AND VITAMIN D OR METHYL DONOR SUPPLEMENTATION ON INFLAMMATION-ASSOCIATED COLON TUMORIGENESIS IN C57BL/6J MICE
Class
Article
Graduation Year
2019
College
College of Agriculture and Applied Sciences
Department
Animal, Dairy, and Veterinary Sciences Department
Faculty Mentor
Abby Benninghoff
Presentation Type
Poster Presentation
Abstract
Previous studies showed that a rodent diet severely depleted in calcium, vitamin D, and methyl donors (folate, vitamin B12, choline, riboflavin, and pyridoxine) promoted intestinal tumorigenesis in mice, whereas restoring calcium and vitamin D blocked this effect. Our research group developed total Western diet (TWD), which is deficient in calcium, vitamin D and many of the methyl donor micronutrients. Consumption of this diet promoted colon tumorigenesis compared to a standard basal diet (AIN93G), and this effect appeared to be mediated primarily by the micronutrient fraction of the diet. In the present study, we hypothesized that restoring calcium and vitamin D (TWD+Ca/VitD) or methyl donor nutrients (TWD+MD) to standard amounts would suppress, at least partially, TWD-induced increases in tumor multiplicity and burden. The azoxymethane+dextran sodium sulfate (AOM+DSS) murine model of inflammation-associated colorectal cancer was employed using male C57BL/6J mice fed AIN93G, TWD, TWD+Ca/VitD or TWD+MD diets for 16 weeks. Endpoints assessed included tumor formation, symptoms of colitis, colon length, cecum weight, and body and fat mass gain. Energy intake in mice fed the TWD+Ca/VitD diet was significantly greater compared to both AIN93G and TWD diets. Notably, the final body weight for mice fed TWD+Ca/VitD was significantly greater than observed for all other diet groups. Also, fat mass was significantly greater in all mice fed the TWD compared to the AIN93G control, whereas adding Ca/VitD or MD did not improve body composition. Restoration of Ca/VitD to standard amounts blocked the promoting effect of TWD on symptoms of colitis, although adding back methyl donors did not affect colitis symptoms. As colitis is a major contributor to colon tumorigenesis, we expect to observe a similar pattern with respect to colon tumor multiplicity and burden. These observations suggest that suboptimal intakes of calcium and vitamin D may contribute to colitis and inflammation-associated colorectal cancer.
Location
North Atrium
Start Date
4-13-2017 10:30 AM
End Date
4-13-2017 11:45 AM
IMPACT OF CALCIUM AND VITAMIN D OR METHYL DONOR SUPPLEMENTATION ON INFLAMMATION-ASSOCIATED COLON TUMORIGENESIS IN C57BL/6J MICE
North Atrium
Previous studies showed that a rodent diet severely depleted in calcium, vitamin D, and methyl donors (folate, vitamin B12, choline, riboflavin, and pyridoxine) promoted intestinal tumorigenesis in mice, whereas restoring calcium and vitamin D blocked this effect. Our research group developed total Western diet (TWD), which is deficient in calcium, vitamin D and many of the methyl donor micronutrients. Consumption of this diet promoted colon tumorigenesis compared to a standard basal diet (AIN93G), and this effect appeared to be mediated primarily by the micronutrient fraction of the diet. In the present study, we hypothesized that restoring calcium and vitamin D (TWD+Ca/VitD) or methyl donor nutrients (TWD+MD) to standard amounts would suppress, at least partially, TWD-induced increases in tumor multiplicity and burden. The azoxymethane+dextran sodium sulfate (AOM+DSS) murine model of inflammation-associated colorectal cancer was employed using male C57BL/6J mice fed AIN93G, TWD, TWD+Ca/VitD or TWD+MD diets for 16 weeks. Endpoints assessed included tumor formation, symptoms of colitis, colon length, cecum weight, and body and fat mass gain. Energy intake in mice fed the TWD+Ca/VitD diet was significantly greater compared to both AIN93G and TWD diets. Notably, the final body weight for mice fed TWD+Ca/VitD was significantly greater than observed for all other diet groups. Also, fat mass was significantly greater in all mice fed the TWD compared to the AIN93G control, whereas adding Ca/VitD or MD did not improve body composition. Restoration of Ca/VitD to standard amounts blocked the promoting effect of TWD on symptoms of colitis, although adding back methyl donors did not affect colitis symptoms. As colitis is a major contributor to colon tumorigenesis, we expect to observe a similar pattern with respect to colon tumor multiplicity and burden. These observations suggest that suboptimal intakes of calcium and vitamin D may contribute to colitis and inflammation-associated colorectal cancer.