2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE INCREASES THE NUMBERSOF TUMORS, CYSTIC CRYPTS AND ABERRANT CRYPT FOCI IN MULTIPLE INTESTINAL NEOPLASIA MICE

The multiple intestinal neoplasia (Min) mice have a mutation in the mu rine adenomatous polyposis coli (Apc) gene rendering them highly susce ptible to spontaneous intestinal adenoma formation, similar to the fam ilial adenomatous polyposis (FAP) syndrome in humans. We studied wheth er the most abundant mutagenic heterocyclic amine isolated from cooked food, 2-amino-1-methyl- 6-phenylimidazo[4,5-b]pyridine (PhIP), could influence early intestinal neoplasia in C57BL/6J-Min/+ and C57BL/6J-+/ + (wild-type) mice of both sexes. PhIP was given in 4 weekly i.p. inje ctions of 50 mg/kg, Ten weeks after the start of the experiment, PhIP had significantly increased the numbers of small tumors and cystic cry pts in the proximal section of the small intestine in male Min/+ mice, and the numbers of aberrant crypt foci (ACF) in the large intestines of both males and females. The effects of PhIP were more pronounced in male than in female Min/+ mice. In +/+ mice, no tumors or cystic cryp ts in the small intestine, and no tumors and only a very few ACF in th e large intestine, were induced by PhIP. These results show that a sub stance frequently present in the human diet is able to enhance the neo plastic process induced by a genetic lesion, which is also commonly fo und both in inherited and sporadic colon carcinomas in humans.