Titel
N-acetyl cysteine alters the genotoxic and estrogenic properties of Alternaria toxins in naturally occurring mixtures
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Abstract
It is unclear if complex mycotoxin mixtures produced by Alternaria spp. act estrogenic and/or genotoxic under physiological conditions, particularly considering the co-occurrence with antioxidants in food. Thus, this study focused on enlightening the impact of N-acetyl cysteine (NAC), as a representative anti-oxidative SH-donor, on the mentioned toxicological endpoints of the signature Alternaria toxins alternariol (AOH), altertoxin-II (ATX-II) and a complex extract (CE) of an Alternaria alternata culture. Using Ishikawa cells as an in vitro model, we monitored alterations in toxin concentrations by LC-MS/MS, estrogenicity by alkaline phosphatase assays, cytotoxicity by sulforhodamine B assays, genotoxicity by single-cell gel electrophoresis and the transcription of selected genes of interest by quantitative real-time PCR. The results indicate that the strong genotoxic effects of epoxide-carrying perylene quinones such as ATX-II are erased in the presence of NAC. The cellular effects of ATX-II/AOH mixtures are dominated by the genotoxicity of the perylene chinone. In this mixture, AOH regained its estrogenicity when co-incubated with NAC. In contrast, NAC treatment of an AOH/CE mixture did not result in a recovery of estrogenicity, but in potentiated anti-estrogenic effects. These findings were in line with gene transcription data, that indicated the aryl hydrocarbon receptor (AhR) to be a prime mediator of Alternaria toxin – induced antagonistic effects towards estrogen receptor signaling. Taken together, further studies on potential endocrine-disruptive properties of non-genotoxic perylene quinones should be a future research priority in the field of these emerging contaminants.
Stichwort
MycotoxinDNA damageXenoestrogenCombinatory toxicologyFood contaminantMixture effects
Objekt-Typ
Sprache
Englisch [eng]
Persistent identifier
phaidra.univie.ac.at/o:1623903
Erschienen in
Titel
Emerging Contaminants
Band
8
ISSN
2405-6650
Erscheinungsdatum
2022
Seitenanfang
30
Seitenende
38
Publication
Elsevier BV
Erscheinungsdatum
2022
Zugänglichkeit
Rechteangabe
© 2022 The Authors

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