title: Bioactivation of food genotoxicants 5-hydroxymethylfurfural and furfuryl alcohol by sulfotransferases from human, mouse and rat: a comparative study.
abstract: 5-Hydroxymethylfurfural (HMF) and furfuryl alcohol (FFA) are moderately potent rodent carcinogens that are present in thermally processed foodstuffs. The carcinogenic effects were hypothesized to originate from sulfotransferase (SULT)-mediated bioactivation yielding DNA-reactive and mutagenic sulfate esters, a confirmed metabolic pathway of HMF and FFA in mice. It is known that orthologous SULT forms substantially differ in substrate specificity and tissue distribution. This could influence HMF- and FFA-induced carcinogenic effects. Here, we studied HMF and FFA sulfoconjugation by 30 individual SULT forms of humans, mice and rats. The catalytic efficiencies (k cat/K M) of HMF sulfoconjugation of human SULT1A1 (13.7 s(-1) M(-1)), mouse Sult1a1 (15.8 s(-1) M(-1)) and 1d1 (4.8 s(-1) M(-1)) and rat Sult1a1 (5.3 s(-1) M(-1)) were considerably higher than those of all other SULT forms investigated (≤0.73 s(-1 )M(-1)). FFA sulfoconjugation was monitored using adenosine as a nucleophilic scavenger for the reactive 2-sulfoxymethylfuran (t 1/2 = 20 s at 37 °C). The resulting adduct N (6)-((furan-2-yl)methyl)-adenosine (N (6)-MF-A) was quantified by isotope-dilution UPLC-MS/MS. The rates of N (6)-MF-A formation showed that hSULT1A1 and its orthologues in mice and rats were also the most important contributors to FFA sulfoconjugation in each of the species. Taken together, the catalytic capacity of hSULT1A1 is comparable to that of mSult1a1 in mice, the species in which carcinogenic effects of HMF and FFA were detected. This is of primary concern due to the expression of hSULT1A1 in many different tissues.
authors.affiliation: Research Group Genotoxic Food Contaminants, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany. sachse@dife.de.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Sachse
authors.affiliation: Department of Nutritional Toxicology, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, 14558, Nuthetal, Germany. meinl@dife.de.
authors.forename: Walter
authors.initials: W
authors.lastname: Meinl
authors.affiliation: Department of Nutritional Toxicology, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, 14558, Nuthetal, Germany. yasmin.sommer@bfr.bund.de.|German Federal Institute for Risk Assessment (BfR), Max-Dohrn-Strasse 8-10, 10589, Berlin, Germany. yasmin.sommer@bfr.bund.de.
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Sommer
authors.affiliation: Department of Nutritional Toxicology, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, 14558, Nuthetal, Germany. glatt@dife.de.
authors.forename: Hansruedi
authors.initials: H
authors.lastname: Glatt
authors.affiliation: Biochemical Institute for Environmental Carcinogens, Prof. Dr. Gernot Grimmer-Foundation, 22927, Grosshansdorf, Germany. albrecht.seidel@biu-grimmer.de.
authors.forename: Albrecht
authors.initials: A
authors.lastname: Seidel
authors.affiliation: Research Group Genotoxic Food Contaminants, German Institute of Human Nutrition (DIfE) Potsdam-Rehbrücke, Arthur-Scheunert-Allee 114-116, 14558, Nuthetal, Germany. monien@dife.de.
authors.forename: Bernhard H
authors.initials: BH
authors.lastname: Monien
mesh_terms: D065767:Activation, Metabolic; D015239:Arylsulfotransferase / Q000378:metabolism*; D002273:Carcinogens / Q000378:metabolism* / Q000633:toxicity; D002384:Catalysis; D002853:Chromatography, Liquid; D005506:Food Contamination; D005662:Furaldehyde / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity; D005663:Furans / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D007527:Isoenzymes; D007700:Kinetics; D011994:Recombinant Proteins / Q000378:metabolism; D018570:Risk Assessment; D013045:Species Specificity; D053719:Tandem Mass Spectrometry
chemical_list: D002273:Carcinogens; D005663:Furans; D007527:Isoenzymes; D011994:Recombinant Proteins; C008046:5-hydroxymethylfurfural; C012986:furfuryl alcohol; D005662:Furaldehyde; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human; C513291:Sult1a1 protein, mouse; C573795:Sult1a1 protein, rat
keywords: 5-Hydroxymethylfurfural; Food carcinogens; Furfuryl alcohol; Sulfotransferase; UPLC-MS/MS