Document Detail

Human exposure to heterocyclic amine food mutagens/carcinogens: relevance to breast cancer.
MedLine Citation:
PMID:  11921178     Owner:  NLM     Status:  MEDLINE    
Heterocyclic amines produced from overcooked foods are extremely mutagenic in numerous in vitro and in vivo test systems. One of these mutagens, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), induces breast tumors in rats and has been implicated in dietary epidemiology studies as raising the risk of breast cancer in humans. Efforts in our laboratory and others have centered on defining the exposure to PhIP and other dietary mutagens derived from cooked food. We accomplish this by analyzing the foods with a series of solid-phase extractions and HPLC. We have developed an LC/MS/MS method to analyze the four major human PhIP metabolites (sulfates and glucuronides) following a single meal containing 27 microg of cooking-produced PhIP in 200 g of grilled meat. Although the intake of PhIP was similar for each of eight women, the total amount excreted in the urine and the metabolite profiles differed among the subjects. It appears that adsorption (digestion) from the meat matrix, other foods in the diet, and genetic differences in metabolism may contribute to the variation. The four major metabolites that can be routinely assayed in the urine are N(2)-OH-PhIP-N(2)-glucuronide, PhIP-N(2)-glucuronide, 4'-PhIP-glucuronide, and N(2)-OH-PhIP-N3-glucuronide. This work is suited to investigate individual exposure and risk, especially for breast cancer, from these potent dietary mutagens.
James S Felton; Mark G Knize; Cynthia P Salmon; Michael A Malfatti; Kristen S Kulp
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.; Review    
Journal Detail:
Title:  Environmental and molecular mutagenesis     Volume:  39     ISSN:  0893-6692     ISO Abbreviation:  Environ. Mol. Mutagen.     Publication Date:  2002  
Date Detail:
Created Date:  2002-03-28     Completed Date:  2002-04-18     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8800109     Medline TA:  Environ Mol Mutagen     Country:  United States    
Other Details:
Languages:  eng     Pagination:  112-8     Citation Subset:  IM    
Molecular and Structural Biology Division, Lawrence Livermore National Laboratory, Livermore, California 94551, USA.
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MeSH Terms
Amines / adverse effects,  analysis
Breast Neoplasms / chemically induced*
Carcinogens / adverse effects*
Food Analysis
Glucuronides / urine
Heterocyclic Compounds / adverse effects,  analysis
Imidazoles / adverse effects*
Meat / analysis
Mutagens / adverse effects*
Grant Support
Reg. No./Substance:
0/Amines; 0/Carcinogens; 0/Glucuronides; 0/Heterocyclic Compounds; 0/Imidazoles; 0/Mutagens; 105650-23-5/2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine

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