The Effects of Diverse Dietary Interventions on Markers of Colon Cancer Risk in Carcinogen-Treated Rodents

Abstract

Colon cancer, a leading cause of cancer-related deaths worldwide, is largely preventable through lifestyle modifications including diet. While epidemiologic evidence associates foods rich in phytochemicals and dietary fiber with a reduced risk of cancer, the chemopreventive efficacy of specific dietary interventions to reduce colon cancer risk is still uncertain. In four studies, this thesis aims to explore the effects of three dietary interventions (red wheat, apiaceous and cruciferous vegetables, and prebiotic dietary fiber) on colon cancer risk in rodents and to characterize the effectiveness of the Total Western diet as a rodent background diet for colon cancer and inflammatory disease models. The first study used a mouse model to explore the effects of different wheat classes and milling fractions on colon cancer prevention. However, the results were inconclusive. Ultimately this mouse model was unsuitable due to challenges with the carcinogen dosage and toxicity, tissue incompatibility with a major biomarker assay, and the limited volume of tissue available for study due to a mouse’s small size. The second study continued this work using a rat model and added the variable of a comparison of background diets: a standard, optimized rodent diet (AIN-93G) or a newer diet based on the typical Western diet (Total Western Diet; TWD). We found some evidence that whole red wheat may reduce CC risk, but only with the TWD background diet, indicating that TWD may be a better background diet for CC rodent models. The third study examined the effects of apiaceous and cruciferous vegetables on colonic inflammation and compared TWD with the Diet Induced Obesity (DIO) model, which uses the same micronutrient concentrations as the AIN-93G diet. Vegetables decreased colon inflammation, but only with the TWD background diet, further supporting its use in modeling lifestyle diseases. The final study examined the effects of prebiotic dietary fibers, including the novel prebiotic fiber polylactose, on CC risk. We found no evidence that polylactose decreases CC risk, but limited evidence that polydextrose decreases CC risk indicates the need for further research in this area. Taken together, these studies expand our understanding of the effect of diet on CC risk by highlighting the detrimental role of mild micronutrient deficiency modeled by the TWD and providing modest support for consuming nutrient rich foods such as whole red wheat, apiaceous and cruciferous vegetables, and prebiotic fibers to reduce CC risk.