Document Detail


Metabolites of 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) in human urine after consumption of charbroiled or fried beef.
MedLine Citation:
PMID:  12351156     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Heterocyclic amines (HAs) are carcinogenic combustion products formed during the cooking of meat at moderate to high temperatures. PhIP is the most common HA formed in fried, grilled or broiled meat, and is a colon, breast, and prostate carcinogen in rodents. The major metabolites of PhIP detected in human urine are N(2)-OH-PhIP-N(2)-glucuronide, PhIP-N(2)-glucuronide, N(2)-OH-PhIP-N(3)-glucuronide, and 4'-PhIP-sulphate. We have measured the time course of PhIP in untreated and acid- or alkali-hydrolyzed urines from 10 healthy non-smoking subjects ingesting identical amounts of char-broiled beef (containing both HAs and PAHs) for 5 days. The morning after the first day of broiled beef consumption (containing 7.7 micro g PhIP), urinary concentration of PhIP increased 14- to 38-fold above mean prefeed concentration. Following cessation of broiled meat consumption, urinary PhIP declined to near prefeed levels within 48-72 h. The ratio of alkali-labile PhIP metabolites to unmetabolized PhIP varied by 2.7-fold among subjects, ranging from 18:1 to 48:1. In a subsequent study we measured PhIP in acid-hydrolyzed urine from 66 subjects ingesting beef pan-fried at high temperature. A significant correlation (r=0.61, P<0.0001) was observed between the amount of fried meat ingested and concentration of PhIP in urines collected between 0 and 12h after feeding. Other investigators have identified 2-OH-PhIP in acid-hydrolyzed urine from these subjects, and also observed a significant correlation (r=0.52, P<0.0001) with the amount of fried meat ingested. Additional studies have measured PhIP metabolites in subjects consuming their normal (unrestricted) diet. PhIP was detected in acid-hydrolyzed urine from 20 to 50% of these subjects, depending on ethnic group. Taken together, these studies indicate that significant amounts of PhIP are bioavailable from ingestion of fried or char-broiled meats, and that urinary PhIP metabolites reflect recent (12-24h) ingestion. Furthermore, significant interindividual differences in the amounts of urinary PhIP metabolite excreted are observed following ingestion of similar amounts of PhIP. These differences do not correlate with interindividual differences in excretion of urinary pyrene metabolites in the same individuals after ingestion of char-broiled beef, indicating that levels of PhIP and pyrene metabolites in human urine are mediated by compound-specific metabolic factors.
Authors:
Paul T Strickland; Zheng Qian; Marlin D Friesen; Nathaniel Rothman; Rashmi Sinha
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.; Review    
Journal Detail:
Title:  Mutation research     Volume:  506-507     ISSN:  0027-5107     ISO Abbreviation:  Mutat. Res.     Publication Date:  2002 Sep 
Date Detail:
Created Date:  2002-09-27     Completed Date:  2002-11-27     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0400763     Medline TA:  Mutat Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  163-73     Citation Subset:  IM    
Affiliation:
Department of Environmental Health Sciences, Johns Hopkins Bloomberg School Public Health, Baltimore, MD 21205, USA.pstrickl@hjsph.edu
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MeSH Terms
Descriptor/Qualifier:
Animals
Carcinogens / administration & dosage,  metabolism*
Chromatography, High Pressure Liquid
Cookery*
Dietary Proteins / administration & dosage
Eating
Glucuronides / urine
Heterocyclic Compounds / adverse effects,  analysis
Humans
Imidazoles / administration & dosage,  metabolism*,  urine*
Meat Products*
Mutagens / metabolism*
Neoplasms / chemically induced,  metabolism
Quinoxalines / urine*
Grant Support
ID/Acronym/Agency:
P01-ES06052/ES/NIEHS NIH HHS; P30-ES03819/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Carcinogens; 0/Dietary Proteins; 0/Glucuronides; 0/Heterocyclic Compounds; 0/Imidazoles; 0/Mutagens; 0/Quinoxalines; 105650-23-5/2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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