title: Conversion of Suspected Food Carcinogen 5-Hydroxymethylfurfural by Sulfotransferases and Aldehyde Dehydrogenases in Postmitochondrial Tissue Preparations of Humans, Mice, and Rats.
abstract: The food contaminant 5-hydroxymethylfurfural (HMF) is formed by heat- and acid-catalyzed reactions from carbohydrates. More than 80% of HMF is metabolized by oxidation of the aldehyde group in mice and rats. Sulfo conjugation yields mutagenic 5-sulfoxymethylfurfural, the probable cause for the neoplastic effects observed in HMF-treated rodents. Considerable metabolic differences between species hinder assessing the tumorigenic risk associated with human dietary HMF uptake. Here, we assayed HMF turnover catalyzed by sulfotransferases or by aldehyde dehydrogenases (ALDHs) in postmitochondrial preparations from liver, kidney, colon, and lung of humans, mice, and rats. The tissues-specific clearance capacities of HMF sulfo conjugation (CL(SC)) and ALDH-catalyzed oxidation (CL(OX)) were concentrated to the liver. The hepatic clearance CL(SC) in mice (males: 487 µl/min/kg bw, females: 2520 µl/min/kg bw) and rats (males: 430 µl/min/kg bw, females: 198 µl/min/kg bw) were considerably higher than those in humans (males: 21.2 µl/min/kg bw, females: 32.2 µl/min/kg bw). The ALDH-related clearance rates CLOX in mice (males: 3400 ml/min/kg bw, females: 1410 ml/min/kg bw) were higher than those of humans (males: 436 ml/min/kg bw, females: 646 ml/min/kg bw) and rats (males: 627 ml/min/kg bw, females: 679 ml/min/kg bw). The ratio of CL(OX) to CL(SC) was lowest in female mice. This finding indicated that HMF sulfo conjugation was most substantial in the liver of female mice, a target tissue for HMF-induced neoplastic effects, and that humans may be less sensitive regarding HMF sulfo conjugation compared with the rodent models.
authors.affiliation: *Research Group Genotoxic Food Contaminants, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, 14558 Nuthetal, Germany; Department of Molecular Toxicology, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, 14558 Nuthetal, Germany; and.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Sachse
authors.affiliation: Department of Molecular Toxicology, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, 14558 Nuthetal, Germany; and.
authors.forename: Walter
authors.initials: W
authors.lastname: Meinl
authors.affiliation: Department of Food Safety, Federal Institute for Risk Assessment (BfR), 10589 Berlin, Germany.
authors.forename: Hansruedi
authors.initials: H
authors.lastname: Glatt
authors.affiliation: *Research Group Genotoxic Food Contaminants, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, 14558 Nuthetal, Germany; Department of Food Safety, Federal Institute for Risk Assessment (BfR), 10589 Berlin, Germany bernhard.monien@bfr.bund.de.
authors.forename: Bernhard H
authors.initials: BH
authors.lastname: Monien
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D005260:Female; D005662:Furaldehyde / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D008658:Inactivation, Metabolic; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D009928:Organ Specificity; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity; D015238:Sulfotransferases / Q000378:metabolism*; D053719:Tandem Mass Spectrometry
chemical_list: D002273:Carcinogens; C008046:5-hydroxymethylfurfural; D005662:Furaldehyde; D000444:Aldehyde Dehydrogenase; D015238:Sulfotransferases
keywords: 5-hydroxymethylfurfural; aldehyde dehydrogenase; metabolism; sulfotransferase