Characterization of a peptide adduct formed by N-acetoxy-2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP), a reactive intermediate of the food carcinogen PhIP

• Published in: Food and chemical toxicology 2004-08, Vol.42 (8), p.1367-1372
• Main Authors: Chepanoske, C.L, Brown, K, Turteltaub, K.W, Dingley, K.H
• Format: Article
• Language: English
• Subjects: acyltransferases; Adduct; Biological and medical sciences; biomarkers; carcinogenesis; Carcinogenesis, carcinogens and anticarcinogens; carcinogenicity; carcinogens; Carcinogens - metabolism; Chemical agents; chemical structure; Chromatography, High Pressure Liquid; cooking; Cysteine - metabolism; DNA adducts; enzyme activity; Food Contamination - analysis; food intake; Food toxicology; genotoxicity; Heterocyclic amine; heterocyclic amines; Humans; Imidazoles - metabolism; Mass Spectrometry; meat; Medical sciences; Models, Biological; Molecular Weight; natural toxicants; peptides; Peptides - metabolism; PhIP; Protein; protein metabolism; Quinolines - metabolism; risk factors; Serum Albumin - metabolism; Spectrometry, Mass, Electrospray Ionization; Structure; sulfotransferases; Toxicology; Tumors
• ISSN: 0278-6915; 1873-6351
• DOI: 10.1016/j.fct.2003.11.012

2-Amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP) is a member of a class of compounds known as the heterocyclic amines (HCAs) that are formed in meat during cooking. It is a multi-organ carcinogen in rodents forms adducts and with DNA and protein. Although protein adducts are not thought to be involved in cancer development, they may be useful as internal dosimeters of PhIP exposure and bioactivation. Towards the goals of characterizing the adducts formed in humans and the development of an assay for quantitation of adduct levels, we have characterized a peptide adduct formed by the putative genotoxic metabolite, N-acetoxy-PhIP. A model peptide with the internal sequence Leu–Gln–Lys–Cys–Pro–Tyr, which is homologous to a potential target sequence for HCAs in human serum albumin, was reacted with N-acetoxy-PhIP and an adduct was identified and further characterized by LC–ESI-MS/MS. N-acetoxy-PhIP is covalently bound to the peptide via cysteine and the exocyclic amino group of PhIP. Future work is needed to establish if this adduct is formed and is stable in vivo in humans following exposure to PhIP.