DNA reactivity of altertoxin II: Identification of two covalent guanine adducts formed under cell-free conditions. (1st October 2020)

• Record Type: Journal Article
• Authors: Soukup, Sebastian T.; Fleck, Stefanie C.; Pfeiffer, Erika; Podlech, Joachim; Kulling, Sabine E.; Metzler, Manfred
• Is Part Of: Toxicology letters. Volume 331(2020)
• Page Start: 75
• Page End: 81
• Publication Date: 2020-10-01
• Subjects: amu atomic mass unit -- AOH alternariol -- AME alternariol methyl ether -- ATX altertoxin -- dA-C8-ABP N-(deoxyadenosin-8-yl)-4-aminobiphenyl -- dC-ATX II-2H2O deoxycytidinyl-ATX II - 2 H2O -- dG-ATX II deoxyguanosinyl-ATX II -- dG-ATX II-2H2O deoxyguanosinyl-ATX II - 2 H2O -- dG-C8-ABP N-(deoxyguanosin-8-yl)-4-aminobiphenyl -- fpg formamidopyrimidine-DNA-glycosylase -- HPRT hypoxanthine guanine phosphoribosyl transferase -- N-OH-ABP N-hydroxy-4-aminobiphenyl -- STTX stemphyltoxin; Altertoxin II -- DNA adduct -- Guanine adduct -- Cytosine adduct -- Alternaria toxin; Toxicology -- Periodicals; 363.179
• DOI: 10.1016/j.toxlet.2020.05.018
• Languages: English
• ISSNs: 0378-4274

Abstract

Highlights: The Alternaria mycotoxin altertoxin II contains an epoxide group. Incubation of altertoxin II with DNA gives rise to three covalent DNA adducts. Two adducts with guanine and one with cytosine were identified by LC–MS. The direct reactivity of altertoxin II with DNA may explain its high mutagenicity. Abstract: Fungi of the genus Alternaria infest many agricultural crops and produce numerous mycotoxins, of which altertoxin II (ATX II) is one of the most mutagenic metabolites. ATX II carries an epoxide group but the formation of DNA adducts has not been demonstrated to date. We report now that ATX II gives rise to two covalent adducts with guanine when incubated with DNA under cell-free conditions. These adducts were demonstrated by LC-high resolution MS after enzymatic degradation of the incubated DNA to deoxynucleosides. The major adduct results from the covalent binding of ATX II, presumably through the epoxide group, to guanine, whereas the minor guanine adduct is derived from the major one by the elimination of two equivalents of water. In addition, a third adduct was detected, formed through covalent binding of ATX II to cytosine followed by the loss of two equivalents of water. The direct DNA reactivity of ATX II may explain its high mutagenicity.