title: DNA adducts induced by food mutagen PhIP in a mouse model expressing human sulfotransferases 1A1 and 1A2.
abstract: Food processing contaminant 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) has previously been shown to induce formation of DNA adducts in vivo. In a previous study the adduct levels were found to increase in a mouse model expressing human (h) sulfotransferases (SULTs) 1A1 and 1A2 after PhIP exposure, detected by (32)P-postlabelling. Isotope dilution ultra performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) is emerging as the method of choice for selective and reproducible detection of known DNA adducts. In the present study we investigated the level and distribution of PhIP induced DNA adducts in male FVB mice 9-11 weeks of age with hSULT mice or wild-type mice (wt) using UPLC-MS/MS. Mice received a single administration of 75 mg/kg bw PhIP by oral gavage, and DNA was analysed 3h after exposure. C8-(2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine- N(2)-yl)-2'-deoxyguanosine (C8-PhIP-dG) adduct levels are significantly higher in PhIP exposed hSULT mice compared with PhIP exposed wt mice. The liver was the least affected organ in wild-type mice, whereas it was the most affected organ in hSULT mice with a 14-fold higher adduct level.
authors.affiliation: Department of Food, Water and Cosmetics, Division of Environmental Medicine, Norwegian Institute of Public Health, 0456 Oslo, Norway.
authors.forename: Anja Hortemo
authors.initials: AH
authors.lastname: Høie
authors.affiliation: Research Group Genotoxic Food Contaminants, Department of Nutritional Toxicology, German Institute of Human Nutrition Potsdam-Rehbrücke, 14558 Nuthetal, Germany; Department of Food Safety, Federal Institute for Risk Assessment, 10589 Berlin, Germany.
authors.forename: Bernhard Hans
authors.initials: BH
authors.lastname: Monien
authors.affiliation: Research Group Genotoxic Food Contaminants, Department of Nutritional Toxicology, German Institute of Human Nutrition Potsdam-Rehbrücke, 14558 Nuthetal, Germany; Department of Food Safety, Federal Institute for Risk Assessment, 10589 Berlin, Germany.
authors.forename: Hansruedi
authors.initials: H
authors.lastname: Glatt
authors.affiliation: Department of Food, Water and Cosmetics, Division of Environmental Medicine, Norwegian Institute of Public Health, 0456 Oslo, Norway.
authors.forename: Hege
authors.initials: H
authors.lastname: Hjertholm
authors.affiliation: Department of Food, Water and Cosmetics, Division of Environmental Medicine, Norwegian Institute of Public Health, 0456 Oslo, Norway. Electronic address: trine.husoy@fhi.no.
authors.forename: Trine
authors.initials: T
authors.lastname: Husøy
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015239:Arylsulfotransferase / Q000235:genetics*; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000493:pharmacokinetics*; D005506:Food Contamination; D006801:Humans; D007093:Imidazoles / Q000493:pharmacokinetics* / Q000633:toxicity*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009153:Mutagens / Q000493:pharmacokinetics / Q000633:toxicity*; D009928:Organ Specificity; D053719:Tandem Mass Spectrometry; D014018:Tissue Distribution
chemical_list: C502239:2-amino-1-methyl-6-phenolimidazo(4,5-b)pyridine-DNA adduct; D018736:DNA Adducts; D007093:Imidazoles; D009153:Mutagens; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human; C513290:SULT1A2 protein, human
keywords: DNA adduct; Food processing contaminant; Genotoxicity; Liquid chromatography; Mass spectrometry; Sulfotransferase