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.