Acute and chronic effect of dietary cholic acid on colonic epithelial cell proliferation.

Administration of cholic acid (1.0% of the diet) to male Fisher rats for 3 days resulted in increased numbers of DNA synthesizing epithelial cells per colonic crypt column as compared to those found in either control or 0.2% cholic acid-fed rats. The middle third of the crypt was the area stimulated to contribute the additional proliferating cells. The maximum number of 3H-TdR-labeled cells was doubled by 24 h and migration had processed further up the colonic crypt of the 1% cholic acid-fed rats than the 0.2% cholic acid or control animals. Compared with cholic acid-deprived rats, long-term dietary intake of 0.2% cholic acid (26 weeks) was found to heighten the numbers of labeled cells per column and expand the proliferative compartment. The enhanced manifestation of colonic neoplasia in MNU-induced rats consuming cholic acid (previously reported by us) appears related to the elevated levels of cell proliferation brought about in response to the deleterious action of the bile acid on the mucosa. Increased numbers of epithelial cells undergoing DNA synthesis in cholic acid-treated animals would allow the earlier expression of malignant transformation in the large intestine.