The Effect of Bile Acids on Colonic Epithelial Cell Proliferation in Rats

The effect of bile acids on the proliferation of colonic epithelial cells was investigated in male Wistar rats. Although a decrease of ^3H-TdR incorporation was observed in bile fistula rats, it increased by intraduodenal administration of deoxycholic acid (DCA) or lithocholic acid (LCA). A promoting effect of ^3H-TdR incorporation was also seen in intrarectal administration of DCA and LCA. The administration of DMH alone increased the ^3H-TdR incorporation. Moreover, the addition of intrarectal DCA or LCA to DMH enhanced the increase markedly. An autoradiographic analysis revealed that the increased ^3H-TdR incorporation was caused by the increase of ^3H-TdR labeled epithelial cells and the enlargement of the proliferative compartment of colonic crypts. On the other hand, cholic acid (CA) and chenodeoxycholic acid (CDCA) had a slight or no effect on ^3H-TdR incorporation. A weekly dose of 30mg/kg of DMH and 5 mg of DCA or LCA for 14 weeks resulted in the development of colonic malignant tumors in 3 out of 8 rats in the former and 1 out of 8 in the latter, while no malignant tumors were found in8 rats when given DMH alone, and it given with CA or CDCA. These findings indicate that DCA and LCA, the secondary bile acids, stimulate colonic epithelial cell proliferation, which is considered to be closely related to the promoting effect of the bile acids on colonic carcinogenesis.