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Epoxide reduction to an alcohol: a novel metabolic pathway for perylene quinone-type alternaria mycotoxins in mammalian cells.

Authors
  • Fleck, Stefanie C
  • Pfeiffer, Erika
  • Podlech, Joachim
  • Metzler, Manfred
Type
Published Article
Journal
Chemical Research in Toxicology
Publisher
American Chemical Society
Publication Date
Feb 17, 2014
Volume
27
Issue
2
Pages
247–253
Identifiers
DOI: 10.1021/tx400366w
PMID: 24428710
Source
Medline
License
Unknown

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.

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