In vivo human metabolism of [2- 14C]2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine (PhIP)

• Published in: Cancer letters Vol. 143; no. 2; pp. 135 - 138
• Main Authors: Lang, Nicholas P., Nowell, Susan, Malfatti, Michael A., Kulp, Kristen S., Knize, Mark G., Davis, Cindy, Massengill, Joyce, Williams, Suzanne, MacLeod, Stewart, Dingley, Karen H., Felton, James S., Turteltaub, Kenneth W.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01.09.1999; Elsevier
• Subjects: 2-Amino-1-methyl-6-phenylimidazo[4,5- b]pyridine; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Carcinogenesis, carcinogens and anticarcinogens; CYP1A2; Foods and miscellaneous; Humans; Imidazoles - administration & dosage; Imidazoles - blood; Imidazoles - toxicity; Imidazoles - urine; Male; Mass Spectrometry; Medical sciences; Metabolism; Mutagens - administration & dosage; Mutagens - metabolism; Mutagens - toxicity; Phenotype; SULT1A1; Tumors; SULT1A1; Phenotype; Metabolism; 2-Amino-1-methyl-6-phenylimidazo[4,5- b]pyridine; CYP1A2; Sulfotransferases; Human; Urine; Aryl sulfotransferase; Enzyme; Digestive system; Metabolite; Transferases; Cytochrome P450; Gut; Carcinogenesis; Pyridine derivatives; Carcinogen; Serum; Colon; Pharmacokinetics; Radiopharmaceuticals; Arylamine; Labelled compound; Food
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/S0304-3835(99)00142-1

To better understand the interactions of the pathways of activation and detoxification on the metabolism of the putative carcinogen, PhIP, we administered a dose of 70–84 μg [2- 14C] PhIP (17.5 μCi 14C) 48–72 h before scheduled colon surgery. Blood and urine collected for the next 48–72 h was evaluated by linear accelerator mass spectroscopy (AMS) and scintillation counting LC-MS to identify specific PhIP metabolites. The thermostable phenol sulfotransferase (SULT1A1) phenotype was correlated with the 4′-PhIP-SO 4 levels in the urine at 0–4 h ( R=0.86, P=0.059). The CYP1A2 activity had a negative correlation with PhIP serum levels at 1 h ( R=0.94, P=0.06) and a positive correlation with urine N-OH-PhIP levels at 0–4 h ( R=0.85, P=0.15). This low level radioisotope method of determining the influence of phenotype on metabolism will significantly improve our understanding of the interrelationships of these pathways and provide a critical foundation for the development of individual risk assessment.