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Toxicol Lett. 2016 Apr 25;248:34-8. doi: 10.1016/j.toxlet.2016.02.017. Epub 2016 Mar 3.

DNA adducts induced by food mutagen PhIP in a mouse model expressing human sulfotransferases 1A1 and 1A2.

Author information

1
Department of Food, Water and Cosmetics, Division of Environmental Medicine, Norwegian Institute of Public Health, 0456 Oslo, Norway.
2
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.
3
Department of Food, Water and Cosmetics, Division of Environmental Medicine, Norwegian Institute of Public Health, 0456 Oslo, Norway. Electronic address: trine.husoy@fhi.no.

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.

KEYWORDS:

DNA adduct; Food processing contaminant; Genotoxicity; Liquid chromatography; Mass spectrometry; Sulfotransferase

PMID:
26940682
DOI:
10.1016/j.toxlet.2016.02.017
[Indexed for MEDLINE]
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