Efficient Method for Rapid Induction of Aberrant Crypt Foci in Rats with 2‐Amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine

Abstract
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‐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‐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.