COLONIC HYPERPROLIFERATION INDUCED IN RATS AND MICE BY NUTRITIONAL-STRESS DIETS CONTAINING 4 COMPONENTS OF A HUMAN WESTERN-STYLE DIET (SERIES 2)

In a previous study colonic hyperplasia and hyperproliferation were induced in mice and rats by a nutritional-stress diet, based on the AIN-76A semisynthetic diet modified to contain four suggested high-risk components of the human Western-style diet: increased fat and phosphate and decreased calcium and vitamin D contents. In this study the effect of raising calcium alone to near the median level (0.22 mg/kcal) and to a high level (1.3 mg/kcal), comparable to adult human dietary intake, was tested in mice and rats while retaining the three other high-risk components. With median calcium intake the nutritional-stress diet induced hyperproliferation of epithelial cells in colonic crypts, with increased numbers of proliferating cells in crypt columns in sigmoid colon of mice (P < 0.001) and rats (P = 0.02) and in the ascending colon of mice (P = 0.01). With high calcium intake, hyperproliferation was reduced almost to control amounts in the presence of unchanged fat, phosphate, and vitamin D.