Acute effects of dietary cholic acid and methylazoxymethanol acetate on colon epithelial cell proliferation; metabolism of bile salts and neutral sterols in conventional and germfree SD rats.

The acute effects of cholic acid ingestion on methylazoxymethanol acetate [(MAM) CAS: 592-62-1]-treated conventional and germfree rats were investigated. Male SD rats were divided into 4 treatment groups. The first group received control chow; the second group, control chow plus 0.5% cholic acid; the third group, control chow plus MAM; and the fourth group, control chow plus 0.5% cholic acid plus MAM. Fecal bile acids, cholesterol, cholesteral degradation products, and neutral sterols, as well as labeling indices and numbers of epithelial cells per crypt column, were measured after 6 weeks of treatment. The administration of MAM to germfree groups diminished both fecal bulk and the amount of fecal water. MAM did not affect the fecal bile acid composition. Analysis of the fecal bile acids in conventional rats fed cholic acid demonstrated that half of the bile acids were in a form of deoxycholic acid. In the germfree groups fed cholic acid, 90% of the bile acids appeared unaltered in the feces. Neither in the germfree nor in the conventional groups was an effect seen of MAM on the output of fecal neutral sterols. The addition of cholic acid to the food decreased the output of neutral sterols both in the conventional (P less than .001) and in the germfree (P less than .02) animals. The germfree animals showed a reduced amount of neutral steroid excretion (P less than .01) when compared to the findings for the conventional groups. MAM had no influence on the fecal cholesterol or coprostanol output. The consumption of 0.5% cholic acid decreased the total output of cholesterol (P less than .05). The excretion of coprostanol was significantly diminished in the conventional rats fed cholic acid (P less than .001). No difference in labeling indices was observed between conventional and germfree rats, whether treated with cholic acid, MAM, or cholic acid plus MAM. However, all germfree groups showed less epithelial cells per crypt column (P less than .001) than did conventional animals.