CARCINOGENICITY OF 2-AMINO-1-METHYL-6-PHENYLIMIDAZO[4,5-B]PYRIDINE (PHIP) IN THE RAT

A total of 10 highly-mutagenic heterocyclic amines have been identifie d to be carcinogenic in rodents. Among these, 2-amino-1-methyl-6-pheny limidazo[4,5-b]pyridine (PhIP), generally the most abundant with norma l cooking procedures, induces mammary and colon carcinomas in rats in a clear dose-dependent manner, In a two-generation exposure (transplac ental and trans-breast milk) experiment using Sprague-Dawley rats, an increased risk of mammary adenocarcinoma development was found in the second generation. Excretion of PhIP into the milk and transfer of PhI P to fetuses and neonates with resultant hepatic PhIP-DNA adduct forma tion were also confirmed. On the other hand PhIP mammary carcinogenesi s was significantly inhibited by coadministration of chlorophyllin or a synthetic antioxidant, 1-O-hexyl-2,3,5-trimethylhydroquinone, in lon g-term experiments using female F344 rats. The available findings stro ngly suggest that this food-derived carcinogen might be of importance as an environmental factor in the production of human cancers and that its carcinogenicity could be largely avoided by reducing intake of su ch compounds or by adoption of appropriate chemopreventive measures.