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Biomonitoring an albumin adduct of the cooked meat carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in humans.
- Source :
- Carcinogenesis; Dec2018, Vol. 39 Issue 12, p1455-1462, 8p
- Publication Year :
- 2018
-
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<superscript>34</superscript> 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- PROSTATE cancer
ALBUMINS
Subjects
Details
- Language :
- English
- ISSN :
- 01433334
- Volume :
- 39
- Issue :
- 12
- Database :
- Complementary Index
- Journal :
- Carcinogenesis
- Publication Type :
- Academic Journal
- Accession number :
- 133871267
- Full Text :
- https://doi.org/10.1093/carcin/bgy125