title: Epoxide reduction to an alcohol: a novel metabolic pathway for perylene quinone-type alternaria mycotoxins in mammalian cells.
abstract: The group of perylene quinone-type Alternaria toxins contains several congeners with epoxide groups, for example, altertoxin II (ATX II) and stemphyltoxin III (STTX III). Recent studies in our laboratory have disclosed that the epoxide moieties of ATX II and STTX III are reduced to alcohols in human colon Caco-2 cells, thereby resulting in the formation of altertoxin I (ATX I) and alteichin, respectively. In the present study, this pathway was demonstrated for ATX II in three other mammalian cell lines. Furthermore, the chemical reaction of this toxin with monothiols like glutathione could be shown, and the structures of the reaction products were tentatively elucidated by UV and mass spectrometry. Chemical reaction of ATX II with dithiols capable of forming five- and six-membered rings gave rise to ATX I, thus providing a clue for the molecular mechanism of the epoxide reduction pathway of ATX II. Both epoxide reduction and glutathione conjugation appear to attenuate, but not completely abolish, the genotoxicity of ATX II.
authors.affiliation: Institute of Applied Biosciences, Unit of Food Toxicology, Karlsruhe Institute of Technology (KIT) , Karlsruhe D-76131, Germany.
authors.forename: Stefanie C
authors.initials: SC
authors.lastname: Fleck
authors.forename: Erika
authors.initials: E
authors.lastname: Pfeiffer
authors.forename: Joachim
authors.initials: J
authors.lastname: Podlech
authors.forename: Manfred
authors.initials: M
authors.lastname: Metzler
mesh_terms: D000111:Acetylcysteine / Q000737:chemistry; D000438:Alcohols / Q000378:metabolism; D000528:Alternaria; D000818:Animals; D001551:Benz(a)Anthracenes / Q000737:chemistry / Q000494:pharmacology*; D018938:Caco-2 Cells; D002460:Cell Line; D003412:Cricetulus; D004249:DNA Damage; D004852:Epoxy Compounds / Q000378:metabolism; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism; D045325:HCT116 Cells; D056945:Hep G2 Cells; D006801:Humans; D009183:Mycotoxins / Q000737:chemistry / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010569:Perylene / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000737:chemistry
chemical_list: D000438:Alcohols; D001551:Benz(a)Anthracenes; D004852:Epoxy Compounds; D009183:Mycotoxins; D013438:Sulfhydryl Compounds; C050234:altertoxin II; C050233:altertoxin I; D010569:Perylene; D005978:Glutathione; D000111:Acetylcysteine