Human exposure to heterocyclic amine food mutagens/carcinogens: Relevance to breast cancer

James S. Felton, Mark G. Knize, Cynthia P. Salmon, Michael A. Malfatti, Kristen S. Kulp

Research output: Contribution to journalArticlepeer-review

69 Scopus citations

Abstract

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 μg 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 N2-OH-PhIP-N2-glucuronide, PhIP-N2-glucuronide, 4′-PhIP-glucuronide, and N2-OH-PhlP-N3-glucuronide. This work is suited to investigate individual exposure and risk, especially for breast cancer, from these potent dietary mutagens.

Original languageEnglish (US)
Pages (from-to)112-118
Number of pages7
JournalEnvironmental and Molecular Mutagenesis
Volume39
Issue number2-3
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • Chemoprevention
  • Dietary mutagen
  • Glucuronide
  • Heterocyclic aromatic amines
  • PhIP
  • Tumorigenicity

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Genetics
  • Genetics(clinical)
  • Toxicology
  • Health, Toxicology and Mutagenesis

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