Genotoxicity of three food processing contaminants in transgenic mice expressing human sulfotransferases 1A1 and 1A2 as assessed by the in vivo alkaline single cell gel electrophoresis assay.
The food processing contaminants 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 5-hydroxymethylfurfural (HMF) and 2,5 dimethylfuran (DMF) are potentially both mutagenic and carcinogenic in vitro and/or in vivo, although data on DMF is lacking. The PHIP metabolite N-hydroxy-PhIP and HMF are bioactivated by sulfotransferases (SULTs). The substrate specificity and tissue distribution of SULTs differs between species. A single oral dose of PhIP, HMF or DMF was administered to wild-type (wt) mice and mice expressing human SULT1A1/1A2 (hSULT mice). DNA damage was studied using the in vivo alkaline single cell gel electrophoresis (SCGE) assay. No effects were detected in wt mice. In the hSULT mice, PhIP and HMF exposure increased the levels of DNA damage in the liver and kidney, respectively. DMF was not found to be genotoxic. The observation of increased DNA damage in hSULT mice compared with wt mice supports the role of human SULTs in the bioactivation of N-hydroxy-PhIP and HMF in vivo.
Department of Food, Water and Cosmetics, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway.
Anja Hortemo
AH
Høie
Department of Food, Water and Cosmetics, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway.
Camilla
C
Svendsen
Department of Chemicals and Radiation, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway.
Gunnar
G
Brunborg
Department of Nutritional Toxicology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.|Department of Food Safety, Federal Institute for Risk Assessment, Berlin, Germany.
Hansruedi
H
Glatt
Office of the Director-General, Norwegian Institute of Public Health, Oslo, Norway.
Jan
J
Alexander
Department of Nutritional Toxicology, German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
Walter
W
Meinl
Department of Food, Water and Cosmetics, Division of Environmental Medicine, Norwegian Institute of Public Health, Oslo, Norway.
Trine
T
Husøy
D000284:Administration, Oral; D000818:Animals; D015239:Arylsulfotransferase / Q000235:genetics*; D020552:Comet Assay / Q000379:methods*; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D005506:Food Contamination; D005511:Food Handling; D005662:Furaldehyde / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000633:toxicity; D005663:Furans / Q000008:administration & dosage / Q000633:toxicity; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000633:toxicity; D008297:Male; D008822:Mice, Transgenic; D009152:Mutagenicity Tests / Q000379:methods*
D005663:Furans; D007093:Imidazoles; C008046:5-hydroxymethylfurfural; C049584:2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine; D005662:Furaldehyde; C037555:2,5-dimethylfuran; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human; C513290:SULT1A2 protein, human
DNA cross linking; DNA strand break; comet assay; furan derivative; heterocyclic amine; sulfotransferase