Mammary gland carcinogenesis by food-derived heterocyclic amines and studies on the mechanisms of carcinogenesis of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP).

The heterocyclic amines (HCAs) comprise a family of mutagenic/carcinogenic compounds found in cooked meat. Several HCAs including 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) are mammary gland carcinogens in rats. One mammary gland carcinogen, PhIP, is the most prevalent in the human diet. This article reviews the mechanisms of mammary gland carcinogenesis of PhIP including metabolic processing, DNA adduct formation, effects on mammary gland development, cell signaling, and the genomic alterations found in PhIP-induced rat mammary gland carcinomas.