title: An in vitro study on the genotoxic effect of substituted furans in cells transfected with human metabolizing enzymes: 2,5-dimethylfuran and furfuryl alcohol.
abstract: 2,5-Dimethylfuran (DMF) and furfuryl alcohol (FFA) are two substituted furans that are formed during the processing of foods and have also been used as food flavorings. DMF and FFA are proposed to be bioactivated by human sulfotransferases (SULTs) which are not expressed in conventional cell lines used for genotoxicity testing. Therefore, in addition to the standard V79 cell line, we used a transfected V79 derived cell line co-expressing human cytochrome P450 (CYP) 2E1 and human SULT1A1 to assess the genotoxicity of DMF and FFA. The alkaline single cell gel electrophoresis (SCGE) assay was used to detect DNA damage in the form of single strand breaks and alkali-labile sites after exposure to DMF (0.5h; 0.5, 1, 1.5 or 2mM) or FFA (3h; 1, 3, 6 or 15mM). DMF induced DNA damage in V79 cells in a concentration-dependent manner irrespective of the expression of human CYP2E1 and SULT1A1. Almost no increase in the level of DNA damage was detected after exposure to FFA, except for a weak effect at the highest concentration in the transfected cell line. The results suggest that DNA damage in V79 cells from exposure to DMF detected by the alkaline SCGE assay is independent of human CYP2E1 and SULT1A1, and the genotoxic effect of FFA, as assessed by SCGE, is minimal in V79 cells.
authors.affiliation: Department of Food, Water and Cosmetics, Norwegian Institute of Public Health (NIPH), NO-0403 Oslo, Norway.
authors.forename: Minor P
authors.initials: MP
authors.lastname: Huffman
authors.affiliation: Department of Food, Water and Cosmetics, Norwegian Institute of Public Health (NIPH), NO-0403 Oslo, Norway.
authors.forename: Anja H
authors.initials: AH
authors.lastname: Høie
authors.affiliation: Department of Food, Water and Cosmetics, Norwegian Institute of Public Health (NIPH), NO-0403 Oslo, Norway.
authors.forename: Camilla
authors.initials: C
authors.lastname: Svendsen
authors.affiliation: Department of Chemicals and Radiation, National Institute of Public Health (NIPH), NO-0403 Oslo, Norway.
authors.forename: Gunnar
authors.initials: G
authors.lastname: Brunborg
authors.affiliation: Institute of Biochemistry, Graz University of Technology, A-8010 Graz, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Murkovic
authors.affiliation: Department of Nutritional Toxicology, German Institute of Human Nutrition, Potsdam-Rehbrücke, 14558 Nuthetal, Germany, and 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, Norwegian Institute of Public Health (NIPH), NO-0403 Oslo, Norway, trine.husoy@fhi.no.
authors.forename: Trine
authors.initials: T
authors.lastname: Husøy
mesh_terms: D000818:Animals; D015239:Arylsulfotransferase / Q000235:genetics / Q000378:metabolism*; D001711:Biotransformation; D002460:Cell Line; D020552:Comet Assay; D003412:Cricetulus; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D005663:Furans / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D009153:Mutagens / Q000633:toxicity*; D014162:Transfection; D019076:Transgenes
chemical_list: D005663:Furans; D009153:Mutagens; D004247:DNA; C012986:furfuryl alcohol; C037555:2,5-dimethylfuran; D019392:Cytochrome P-450 CYP2E1; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human