EFFICIENT METHOD FOR RAPID INDUCTION OF ABERRANT CRYPT FOCI IN RATS WITH 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) induces aberran t crypt foci (ACFs) as well as colon cancer in F344 male rats. Conditi ons allowing rapid development of ACFs over a short period were invest igated. F344 male rats were fed 400 ppm of PhIP . HCl in a low-fat die t (LF) for 2 weeks and then given a PhIP-free, high-fat diet containin g PRIMEX (HF-PR) or safflower oil, or PhIP-free LF for 4 or 12 weeks. Rats fed HF-PR for 4 weeks gave the highest number of ACFs/rat (3.3) a nd their size in terms of aberrant crypts/ACF(2.7) was much larger tha n that obtained with conventional continuous feeding of PhIP for 25 we eks in the CE-2 diet. Therefore, 2 weeks of dietary exposure to 400 pp m of PhIP . HCl, followed by HF-PR for 4 weeks, is a practical and con venient method for obtaining ACFs. This protocol should be useful for studies of the early phase of colon carcinogenesis.