REDUCTION OF ABERRANT CRYPT FOCI INDUCED IN RAT COLON WITH AZOXYMETHANE OR METHYLNITROSOUREA BY FEEDING CHOLIC-ACID

Recent studies in our laboratory have demonstrated that feeding cholic acid (CHA) to rats treated with a single dose of azoxymethane (AOM) reduces the growth of putative preneoplastic lesions, aberrant crypt foci (ACF), in a dose-dependent manner [1]. This finding was unexpected since CHA has been reported to promote colon cancer in rats receiving multiple treatments of the colon carcinogen, methylnitrosourea (MNU). The main objective of the present investigation was to evaluate the effect of the type of carcinogen and treatment protocol on the induction and growth of ACF in conjunction with CHA treatment Male Sprague - Dawley rats received 0, 1 or 2 treatments with AOM or MNU and were fed either the AIN-76A or AIN- 76A plus 0.2% CHA diet for 4 weeks. The total number and average size of ACF were significantly reduced in CHA-fed animals regardless of the type or number of treatments of carcinogen. The greatest reduction of ACF due to CHA-feeding was seen in the distal colon. The average crypt multiplicity (number of crypts in each ACF) was not altered by diet or carcinogen treatment. Colonic cell proliferation (crypt height and number of mitotic figures) was significantly increased in CHA-fed animals compared to control diet animals. Therefore, feeding CHA for 4 weeks reduced the number and size of ACF in rats induced by 1 or 2 injections of AOM or MNU, despite stimulation of colonic cell proliferation. These findings suggest further investigation is needed to understand the mechanism of promotion by cholic acid and the value of number and growth characteristics of ACF as a biological endpoint in the pathogenesis of colon cancer.