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N-acetyl cysteine alters the genotoxic and estrogenic properties of Alternaria toxins in naturally occurring mixtures

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Emerging Contaminants 2022年第1期8卷 30-38页

作者： Georg Aichinger Dino Grgic julia beisl Francesco Crudo Benedikt Warth Elisabeth Varga Doris Marko Department of Food Chemistry and Toxicology University of ViennaAustria Department of Health Sciences and Technology ETH ZurichSwitzerland

It is unclear if complex mycotoxin mixtures produced by Alternaria *** estrogenic and/or genotoxic under physiological conditions,particularly considering the co-occurrence with antioxidants in ***,this study focused on enlightening the impact of N-acetyl cysteine(NAC),as a representative antioxidative 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 *** 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 realtime *** results indicate that the strong genotoxic effects of epoxide-carrying perylene quinones such as ATX-II are erased in the presence of *** cellular effects of ATX-II/AOH mixtures are dominated by the genotoxicity of the perylene *** this mixture,AOH regained its estrogenicity when coincubated with *** contrast,NAC treatment of an AOH/CE mixture did not result in a recovery of estrogenicity,but in potentiated anti-estrogenic *** findings were in line with gene transcription data,that indicated the aryl hydrocarbon receptor(AhR)to be a prime mediator of Alternaria toxin e induced antagonistic effects towards estrogen receptor *** 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.

关键词： Mycotoxin DNA damage Xenoestrogen Combinatory toxicology Food contaminant Mixture effects

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