FURTHER INVESTIGATION OF THE EFFECT OF CHOLIC-ACID ON THE INDUCTION, GROWTH-CHARACTERISTICS AND STABILITY OF ABERRANT CRYPT FOCI IN RAT COLON

We previously reported that the colons of animals injected with azoxym ethane (AOM) and fed a diet containing cholic acid (CHA) had lower num bers of aberrant crypt foci (ACF) than those in animals fed a control diet. To follow up on this observation, a series of studies was conduc ted to determine whether CHA affects the development of ACF in a dose- and time-dependent manner, and the possible mechanism(s) involved. Sp rague Dawley male rats were injected with AOM (20 mg/kg s.c.), and one week later randomly allocated to groups fed diets containing 0, 0.05, 0.1 or 0.2% CHA by weight, for 4 weeks. Their colons were scored for the number, size and location of ACF, number of crypts per ACF, and mi totic activity. It was observed that the number and size of ACF decrea sed with increasing levels of CHA. Mitotic activity was higher (P < 0. 05) in the 0.2% CHA diet (CHA-diet) group compared to the 0% CHA group . To determine if timing of intervention with the CHA-diet was critica l, rats were allocated to the CHA-diet before or after AOM injection. The ACF-reducing effect of 0.2% CHA diet was evident (P less than or e qual to 0.05) only after AOM injection. Intervention with the CHA-diet 4 weeks after AOM injection demonstrated that the diet eliminated and /or remodelled a large proportion (50%) of ACF which had developed wit hin 4 weeks and inhibited the growth of those ACF that persisted. This effect was also associated with higher (P less than or equal to 0.05) mitotic activity in the colon. Discontinuing the treatment of rats wi th the CHA-diet resulted in a rapid increase in the number of ACF in t heir colons, establishing that the growth inhibitory effect of the CHA -diet on ACF was reversible. In conclusion, it was demonstrated that t he CHA-diet modulated the number of ACF by inhibiting their developmen t and growth and by eliminating or remodelling a selected population o f ACF.