An Endogenous Colon Mitosis Inhibitor and Dietary Calcium Inhibit the Increased Colonic Cell Proliferation Induced by Cholic Acid

Abstract

We have previously reported that a single intraperitoneal injection of the tripeptide pGlu-His-GlyOH (colon mitosis inhibitor (CMI] is followed by a transient reduction of cell proliferation in the colonic epithelium in mice. The effect of the tripeptide on accelerated cell proliferation in the colonic epithelium was tested during the acute response of the epithelial cells to a diet supplemented with cholic acid. The kinetics of this response was first examined with different amounts of calcium in the feed. We found an increased labeling index (LI) and mitotic rate 2 days after changing the diet, and this response was stronger in animals with a low-calcium cholic acid diet than in animals with cholic acid diet with a standard amount of calcium or a high-calcium cholic acid diet. After 2 weeks of treatment cell proliferation remained significantly elevated only in the animals with low-calcium cholic acid diet. The effect of CMI was tested 7 days after the change to a low-calcium cholic acid diet. Under these conditions a single dose of CMI (10(-12) mol per animal) was still followed by a transient reduction in the proliferative indices in the colonic epithelium. However, the decreases in LI was observed earlier after CMI treatment (at 2 h) in the animals fed a low-calcium cholic acid than in animals with a standard diet.