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 aberrant crypt foci (ACFs) as well as colon cancer in F344 male rats. Conditions allowing rapid development of ACFs over a short period were investigated. F344 male rats were fed 400 ppm of PhIP x HCl in a low-fat diet (LF) for 2 weeks and then given a PhIP-free, high-fat diet containing 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) and their size in terms of aberrant crypts/ACF (2.7) was much larger than that obtained with conventional continuous feeding of PhIP for 25 weeks in the CE-2 diet. Therefore, 2 weeks of dietary exposure to 400 ppm of PhIP x HCl, followed by HF-PR for 4 weeks, is a practical and convenient method for obtaining ACFs. This protocol should be useful for studies of the early phase of colon carcinogenesis.