INTESTINAL MUTAGENICITY OF 2 CARCINOGENIC FOOD MUTAGENS IN TRANSGENICMICE - 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE AND AMINO(ALPHA)CARBOLINE

The heterocyclic amines produced during the cooking of meat, including amino(alpha)carboline (A alpha C) and 2-amino-1-methyl-6-phenylimidaz o[4,5-b]pyridine (PhIP), are potent bacterial mutagens and are carcino genic in rodents. PhIP is mutagenic in the small intestine, but its mu tagenicity in the colon, where most human intestinal cancers arise, ha s not been reported, nor has the mutagenicity of A alpha C. In this st udy, A alpha C (800 p.p.m.) was fed for 30 and 45 days and PhIP (100 a nd 400 p.p.m.) was fed for 30, 60 and 90 days to groups of F-1 (C57BL/ 6xSWR) mice hemizygous for multiple tandem copies of a lad transgene ( the Big Blue(TM) mouse) and heterozygous at the endogenous Dlb-1 locus , The mutant frequencies were assayed at Dlb-1 and at lad in the small intestine and at lacI in the colon, PhIP induced mutations at both lo ci in the small intestine and induced slightly fewer mutations in the colon, The accumulation of mutations at both loci appears to be linear with both PhIP concentration and duration of exposure and, thus, with dose(concentration x duration). The linear increase with time is in a greement with predictions about the effectiveness of chronic treatment protocols for tests of in vivo mutagenicity, Unlike PhIP, A alpha C i nduced mutations specifically in the colon and not in the small intest ine, thereby showing a dramatic tissue specificity, The rate (mutation s/p.p.m. day) was similar to PhIP.