DNA and protein adduct formation in the colon and blood of humans after exposure to a to dietary-relevant dose of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.
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 mug) 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. (...)
Mots-clés Pascal : Tumeur maligne, Côlon, Carcinogène, Amine, Composé aromatique, Régime alimentaire, Plasma sanguin, Epidémiologie, Marqueur biologique, Facteur risque, Technique, Homme, Appareil digestif pathologie, Intestin pathologie, Côlon pathologie
Mots-clés Pascal anglais : Malignant tumor, Colon, Carcinogen, Amine, Aromatic compound, Diet, Blood plasma, Epidemiology, Biological marker, Risk factor, Technique, Human, Digestive diseases, Intestinal disease, Colonic disease
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 99-0413510
Code Inist : 002B13B01. Création : 22/03/2000.