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

Nicholas P. Lang, Susan Nowell, Michael A. Malfatti, Kristen S. Kulp, Mark G. Knize, Cindy Davis, Joyce Massengill, Suzanne Williams, Stewart MacLeod, Karen H. Dingley, James S. Felton, Ken W Turteltaub

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

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 70-84μg [2-14C] PhIP (17.5μCi 14C) 48-72h before scheduled colon surgery. Blood and urine collected for the next 48-72h 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-SO4 levels in the urine at 0-4h (R=0.86, P=0.059). The CYP1A2 activity had a negative correlation with PhIP serum levels at 1h (R=0.94, P=0.06) and a positive correlation with urine N-OH-PhIP levels at 0-4h (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. Copyright (C) 1999 Elsevier Science Ireland Ltd.

Original languageEnglish (US)
Pages (from-to)135-138
Number of pages4
JournalCancer Letters
Volume143
Issue number2
DOIs
StatePublished - Sep 1999
Externally publishedYes

Keywords

  • 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
  • CYP1A2
  • Metabolism
  • Phenotype
  • SULT1A1

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

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    Lang, N. P., Nowell, S., Malfatti, M. A., Kulp, K. S., Knize, M. G., Davis, C., Massengill, J., Williams, S., MacLeod, S., Dingley, K. H., Felton, J. S., & Turteltaub, K. W. (1999). In vivo human metabolism of [2-14C]2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Cancer Letters, 143(2), 135-138. https://doi.org/10.1016/S0304-3835(99)00142-1