Comparative effects of secondary bile acids, deoxycholic and lithocholic acids, on aberrant crypt foci growth in the postinitiation phases of colon carcinogenesis

Abstract

The objective of this study was to investigate the effect of deoxycholic (DCA) and lithocholic (LCA) acids on the postinitiation phases of colon cancer. Male Sprague‐Dawley rats (n = 170) were injected with azoxymethane (2 injections at 15 mg/kg body wt sc given 1 wk apart) and fed a control (CON) AIN‐93 diet. Two weeks after the second azoxymethane injection, 10 animals were killed and aberrant crypt foci (ACF) were enumerated. The remaining animals were randomly assigned to four diet groups: 1) CON, 2) DCA, 3) LCA, and 4) high fat (HF, a positive control group). Bile acid diets consisted of 0.2% by weight DCA or LCA; HF diets consisted of 20% fat (5% soybean oil + 15% beef tallow by weight). Animals were killed at Weeks 3, 12, and 20 (from 1st carcinogen injection), and number and growth features of ACF and adenomatous lesions were enumerated in the colon. At Week 12, ACF number and small, medium, and large (1–3, 4–6, and ≥7 crypts/focus, respectively) ACF were higher in the HF group than in the DCA, LCA, and CON groups (p ≤ 0.05). By Week 20, ACF number and small, medium, and large ACF were similar in the LCA and HF groups, whereas the response was similar in the DCA and CON groups. Average crypt multiplicity was higher in the HF and LCA groups than in the DCA and CON groups (p ≤ 0.05). Microadenoma (MA) incidence was higher in the HF group than in the CON and LCA groups (p ≤ 0.05). Regional distribution patterns for ACF number were similar to MA and tumor distribution patterns within the CON, DCA, and HF groups. In the LCA group, ACF number and MA showed a proximal predominance in regional distribution, whereas tumors showed a distal predominance. HF diets provided the most stimulatory environment, immediately enhancing the number and growth of ACF and MA incidence. In conclusion, HF and LCA diets exerted distinct effects on postinitiation phases of colon cancer, whereas the DCA diet did not.