Biomonitoring an albumin adduct of the cooked meat carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5- b ]pyridine in humans

Medjda Bellamri, Yi Wang, Kim Yonemori, Kami K. White, Lynne R. Wilkens, Loïc Le Marchand, Robert J. Turesky

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is formed in cooked meats and may be linked to dietary-associated colorectal, prostate and mammary cancers. Genotoxic N-oxidized metabolites of PhIP react with the Cys 34 of albumin (Alb) to form a sulfinamide adduct, a biomarker of the biologically effective dose. We examined the kinetics of PhIP-Alb adduct formation in plasma of volunteers on a 4-week semicontrolled diet of cooked meat containing known quantities of PhIP. The adduct was below the limit of detection (LOD) (10 femtograms PhIP/mg Alb) in most subjects before the meat feeding but increased by up to 560-fold at week 4 in subjects who ate meat containing 8.0 to 11.7 μg of PhIP per 150-200 g serving. In contrast, the adduct remained below the LOD in subjects who ingested 1.2 or 3.0 μg PhIP per serving. Correlations were not seen between PhIP-Alb adduct levels and PhIP intake levels (P = 0.76), the amount of PhIP accrued in hair (P = 0.13), the amounts of N-oxidized urinary metabolites of PhIP (P = 0.66) or caffeine CYP1A2 activity (P = 0.55), a key enzyme involved in the bioactivation of PhIP. The half-life of the PhIP-Alb adduct was <2 weeks, signifying that the adduct was not stable. PhIP-Alb adduct formation is direct evidence of bioactivation of PhIP in vivo. However, the PhIP hair biomarker is a longer lived and more sensitive biomarker to assess exposure to this potential human carcinogen.

Original languageEnglish (US)
Pages (from-to)1455-1462
Number of pages8
JournalCarcinogenesis
Volume39
Issue number12
DOIs
StatePublished - Dec 31 2018

Bibliographical note

Funding Information:
This research was supported by grant R01CA122320 (R.J.T.). Mass spectrometry was carried out in the Analytical Biochemistry Shared Resource of the Masonic Cancer Center, University of Minnesota, funded in part by Cancer Center Support Grant CA-077598

Funding Information:
This research was supported by grant R01CA122320 (R.J.T.). Mass spectrometry was carried out in the Analytical Biochemistry Shared Resource of the Masonic Cancer Center, University of Minnesota, funded in part by Cancer Center Support Grant CA-077598. Conflict of Interest Statement: None declared.

Publisher Copyright:
© The Author(s) 2018. Published by Oxford University Press. All rights reserved.

Fingerprint

Dive into the research topics of 'Biomonitoring an albumin adduct of the cooked meat carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5- b ]pyridine in humans'. Together they form a unique fingerprint.

Cite this