Growth features of aberrant crypt foci that resist modulation by cholic acid

Previously, we demonstrated that feeding rats a diet containing 0.2% cholic acid (CHA-diet) resulted in the elimination or remodelling of a number of aberrant crypt foci (ACF) in their primal stages (1-3 crypts/focus). The present investigation was conducted to determine if ACF with advanced growth features will respond differently than their primal counterparts to the CHA-diet. Sprague-Dawley male rats were injected with azoxymethane (20 mg/ kg) and were maintained on a control diet for 21 weeks. At week 21, three rats were killed and their colons were assessed for ACE. The remaining animals were randomly divided into two groups, which were fed a control diet or a CHA-diet respectively, After 3 weeks of feeding, the rats (n = 5) were killed and their colons were assessed for the number, size (area occupied by each focus) and crypt multiplicity (number of crypts/focus). The CHA-diet resulted in a significant (P 4 crypts/focus, a 50.4% reduction. Treatment with CHA resulted in a marked reduction in the population of ACF with 1-2 or 3-4 crypt multiplicity with area >5-1Ox10(-2) mm2. These findings demonstrate that ACF with advanced growth features are phenotypically different from their primal counterparts in resisting the responses elicited by the CHA-diet even at a late time point, and that morphological heterogeneity among ACF may represent different biological states.