DNA and protein adduct formation in the colon and blood of humans after exposure to a dietary-relevant dose of 2-amino-1-methyl-6-phenylimidazo[4,5- b]pyridine

Karen H. Dingley, Kellie D. Curtis, Susan Nowell, James S. Felton, Nicholas P. Lang, Ken W Turteltaub

Research output: Contribution to journalArticlepeer-review

160 Scopus citations

Abstract

Epidemiology studies have indicated that certain dietary components, including well-cooked meat, are risk determinants for colon cancer. Cooked meat can contain significant quantities of heterocyclic aromatic amines (HCAs), which have been established as carcinogens in laboratory animals. 2- Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is usually the most mass-abundant HCA, with concentrations up to 480 ppb. We used accelerator mass spectrometry to establish whether DNA and protein adducts can be detected in humans exposed to a quantity of PhIP comparable with levels of exposure that occur in the diet. Five human volunteers were administered a dietary-relevant dose of [14C]PhIP (70-84 μg) 48-72 h before surgery for removal of colon tumors. Blood samples were collected at various time points, and albumin, hemoglobin, and WBC DNA were extracted for analysis by accelerator mass spectrometry. Tissue samples were collected during surgery and used to assess either tissue available doses of [14C]PhIP or adduct levels. The results of this study show: (a) PhIP is activated to a form that will bind to albumin, hemoglobin, and WBC DNA in peripheral blood. WBC DNA adducts were unstable and declined substantially over 24 h; (b) PhIP is bioavailable to the colon, with levels in normal tissue in the range 42-122 pg PhIP/g tissue; and (c) PhIP binds to both protein and DNA in the colon. DNA adduct levels in the normal tissue were 35-135 adducts/1012 nucleotides, which was significantly lower than tumor tissue. The results of this study demonstrate that PhIP is bioavailable to the human colon following defined dietary-relevant doses and forms DNA and protein adducts.

Original languageEnglish (US)
Pages (from-to)507-512
Number of pages6
JournalCancer Epidemiology Biomarkers and Prevention
Volume8
Issue number6
StatePublished - 1999
Externally publishedYes

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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