title: Bioactivation of 5-hydroxymethyl-2-furaldehyde to an electrophilic and mutagenic allylic sulfuric acid ester.
abstract: 5-Hydroxymethyl-2-furaldehyde (HMF), a ubiquitous food contaminant, has been proposed to be metabolically activated through sulfonation of its allylic hydroxyl functional group. In support of this idea, we have found the strong direct mutagenicity of chemically synthesized sulfuric acid ester, 5-sulfooxymethylfurfural (SMF), in Salmonella typhimurium TA104. The intrinsic mutagenicity of this reactive ester was significantly inhibited by glutathione and glutathione S-transferase activity in dialyzed rat liver cytosol. The metabolic formation of SMF was elucidated by enhanced mutagenicity of HMF in the presence of rat hepatic cytosol enriched with the sulfo-group donor, 3'-phosphoadenosine-5'-phosphosulfate (PAPS). The PAPS- and cytosol-dependent mutagenicity of HMF was markedly lessened by sulfotransferase inhibitors such as 2,6-dichloro-4-nitrophenol and dehydroepiandrosterone. These results suggest that HMF can be metabolically activated to an allylic sulfuric acid ester which may play a role as an ultimate electrophilic metabolite in toxification of the parent compound in vivo.
authors.affiliation: Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Connecticut 06520-8034, USA.
authors.forename: Y C
authors.initials: YC
authors.lastname: Lee
authors.forename: M
authors.initials: M
authors.lastname: Shlyankevich
authors.forename: H K
authors.initials: HK
authors.lastname: Jeong
authors.forename: J S
authors.initials: JS
authors.lastname: Douglas
authors.forename: Y J
authors.initials: YJ
authors.lastname: Surh
mesh_terms: D000818:Animals; D001711:Biotransformation; D003600:Cytosol / Q000201:enzymology; D003687:Dehydroepiandrosterone / Q000494:pharmacology; D005662:Furaldehyde / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D005978:Glutathione / Q000494:pharmacology; D005982:Glutathione Transferase / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology; D009152:Mutagenicity Tests; D009153:Mutagens / Q000494:pharmacology*; D009596:Nitrophenols / Q000494:pharmacology; D010724:Phosphoadenosine Phosphosulfate / Q000378:metabolism; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects*; D015238:Sulfotransferases / Q000037:antagonists & inhibitors; D013464:Sulfuric Acids / Q000378:metabolism
chemical_list: D009153:Mutagens; D009596:Nitrophenols; D013464:Sulfuric Acids; D003687:Dehydroepiandrosterone; D010724:Phosphoadenosine Phosphosulfate; C015802:2,6-dichloro-4-nitrophenol; C008046:5-hydroxymethylfurfural; D005662:Furaldehyde; D005982:Glutathione Transferase; D015238:Sulfotransferases; D005978:Glutathione