Colonic hyperplasia and hyperproliferation induced by a nutritional stress diet with four components of Western-style...

We studied the effects of specific nutritional modifications on colonic epithelial cell proliferation in mice and rats. The nutritional stress diet developed for this study was based on the AIN (American Institute of Nutrition)-76A semisynthetic diet, modified to contain four suggested risk factors of the human Western-style diet: increased fat and phosphate and decreased calcium and vitamin D content. We fed diets to mice and rats for 12 weeks beginning at 3 weeks of age. Hyperplasia developed in both sigmoid and ascending colon of mice and rats with lengthening of colonic crypts. Hyperproliferation developed in the sigmoid colon of mice and rats, and in the ascending colon of rats, with increased [3H]thymidine-labeling of epithelial cells. Thus, in colonic mucosa, the nutritional stress diet, which included risk factors of a Western-style diet, induced changes that occur in carcinogen-induced rodent models and in humans who are at increased risk for colonic neoplasia.