Carcinogenesis, Vol. 21, No. 11, 2065-2072,
November 2000
© 2000 Oxford University Press
Carcinogenesis |
Identification of urine metabolites of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine following consumption of a single cooked chicken meal in humans
Biology and Biotechnology Research Program, L-452, Lawrence Livermore National Laboratory, Livermore, CA 94550, USA
Many studies suggest that mutagenic/carcinogenic chemicals in the diet, like 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), may play a role in human cancer initiation. We have developed a method to quantify PhIP metabolites in human urine and have applied it to samples from female volunteers who had eaten a meal of cooked chicken. For this analysis, urine samples (5 ml) were spiked with a deuterium-labeled internal standard, adsorbed to a macroporous polymeric column and then eluted with methanol. After a solvent exchange to 0.01 M HCl, the urine extracts were passed through a filter, applied to a benzenesulfonic acid column, washed with methanol/acid and eluted with ammonium acetate and concentrated on a C18 column. The metabolites were eluted from the C18 column and quantified by LC/MS/MS. In our studies of human PhIP metabolism, eight volunteers were fed 200 g of cooked chicken containing a total of 27 µg PhIP. Urine samples were collected for 24 h after the meal, in 6 h aliquots. Although no metabolites could be found in urine collected from volunteers before eating the chicken, four major human PhIP metabolites, N2-OH-PhIP-N2-glucuronide, PhIP-N2-glucuronide, 4'-PhIP-sulfate and N2-OH-PhIP-N3-glucuronide, were found in the urine after the chicken meal. The volunteers in the study excreted 4–53% of the ingested PhIP dose in the urine. The rate of metabolite excretion varied among the subjects, however, in all of the subjects the majority of the metabolites were excreted in the first 12 h. Very little metabolite was detected in the urine after 18 h. In humans, N2-OH-PhIP-N2 glucuronide is the most abundant urinary metabolite, followed by PhIP-N2-glucuronide. The variation seen in the total amount, excretion time and metabolite ratios with our method suggests that individual digestion, metabolism and/or other components of the diet may influence the absorption and amounts of metabolic products produced from PhIP.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. W. Dellinger, G. Chen, A. S. Blevins-Primeau, J. Krzeminski, S. Amin, and P. Lazarus Glucuronidation of PhIP and N-OH-PhIP by UDP-glucuronosyltransferase 1A10 Carcinogenesis, November 1, 2007; 28(11): 2412 - 2418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Tang, J. J. Liu, A. Rundle, C. Neslund-Dudas, A. T. Savera, C. H. Bock, N. L. Nock, J. J. Yang, and B. A. Rybicki Grilled Meat Consumption and PhIP-DNA Adducts in Prostate Carcinogenesis Cancer Epidemiol. Biomarkers Prev., April 1, 2007; 16(4): 803 - 808. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Malfatti, E. A. Ubick, and J. S. Felton The impact of glucuronidation on the bioactivation and DNA adduction of the cooked-food carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in vivo Carcinogenesis, November 1, 2005; 26(11): 2019 - 2028. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J Gibney, M. Walsh, L. Brennan, H. M Roche, B. German, and B. van Ommen Metabolomics in human nutrition: opportunities and challenges Am. J. Clinical Nutrition, September 1, 2005; 82(3): 497 - 503. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. G. Walters, P. J. Young, C. Agus, M. G. Knize, A. R. Boobis, N. J. Gooderham, and B. G. Lake Cruciferous vegetable consumption alters the metabolism of the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) in humans Carcinogenesis, September 1, 2004; 25(9): 1659 - 1669. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Fang, R. J. Edwards, M. Bartlet-Jones, G. W. Taylor, S. Murray, and A. R. Boobis Urinary N2-(2'-deoxyguanosin-8-yl)PhIP as a biomarker for PhIP exposure Carcinogenesis, June 1, 2004; 25(6): 1053 - 1062. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Zhu, P. Chang, M. L. Bondy, A. A. Sahin, S. E. Singletary, S. Takahashi, T. Shirai, and D. Li Detection of 2-Amino-1-Methyl-6-Phenylimidazo[4,5-b]-Pyridine-DNA Adducts in Normal Breast Tissues and Risk of Breast Cancer Cancer Epidemiol. Biomarkers Prev., September 1, 2003; 12(9): 830 - 837. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. S. Hecht Human urinary carcinogen metabolites: biomarkers for investigating tobacco and cancer Carcinogenesis, June 1, 2002; 23(6): 907 - 922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W.G. Stillwell, R. Sinha, and S.R. Tannenbaum Excretion of the N2-glucuronide conjugate of 2-hydroxyamino-1-methyl-6-phenylimidazo[4,5-b]pyridine in urine and its relationship to CYP1A2 and NAT2 activity levels in humans Carcinogenesis, May 1, 2002; 23(5): 831 - 838. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Langouet, A. Paehler, D. H. Welti, N. Kerriguy, A. Guillouzo, and R. J. Turesky Differential metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in rat and human hepatocytes Carcinogenesis, January 1, 2002; 23(1): 115 - 122. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Malfatti and J. S. Felton N-Glucuronidation of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine (PhIP) and N-hydroxy-PhIP by specific human UDP-glucuronosyltransferases Carcinogenesis, July 1, 2001; 22(7): 1087 - 1093. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bardelli, D. P. Cahill, G. Lederer, M. R. Speicher, K. W. Kinzler, B. Vogelstein, and C. Lengauer Carcinogen-specific induction of genetic instability PNAS, April 5, 2001; (2001) 81082898. [Abstract] [Full Text]
|
|
|
|
|
|
A. Bardelli, D. P. Cahill, G. Lederer, M. R. Speicher, K. W. Kinzler, B. Vogelstein, and C. Lengauer From the Cover: Carcinogen-specific induction of genetic instability PNAS, May 8, 2001; 98(10): 5770 - 5775. [Abstract] [Full Text] [PDF]
|
|