Effects of sodium cholate on experimental carcinogenesis and cell proliferation in an excluded colonic segment.

Abstract

Bile salts appear to be important promoters of colon carcinogenesis. This study was designed to assess the importance of the fecal stream in cholic acid-induced colon tumor promotion. Male Sprague-Dawley rats underwent transverse colostomy after induction with dimethylhydrazine (DMH) and the excluded distal colon was irrigated with saline or sodium cholate (23 microM) 5 times per week until sacrifice. Controls initially injected with saline were similarly treated. All surviving animals were sacrificed at 28 weeks after the last DMH injection. Five animals from each group were randomly chosen to assess tritiated thymidine labeling and distribution by autoradiography in normal appearing colon mucosa of irrigated bowel. Cholate irrigation failed to increase tumor yield or modify the proportion of adenomas and adenocarcinomas in this model. Paradoxically, fewer tumors per affected rat were noted with sodium cholate irrigation. Cholate irrigation also failed to affect crypt cellularity, thymidine labeling indices, and labeling distribution in DMH-treated rats and controls. An effect of DMH was seen, however, with an increase in thymidine labeling index and increased labeling in the top half of the crypt in all DMH-treated groups. This study suggests that tumor promotion with primary bile salts is not a direct affect and may result from further bile salt metabolism within the fecal stream. DMH-induced changes in cell proliferation were reproduced with this model. Use of an excluded colon segment to assess the effect of suspected tumor promoters on carcinogenesis or colon mucosal cell proliferation is feasible and may be a useful model for future studies.