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 stud...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 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 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 realtime 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 coincubated 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 e 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.展开更多
文摘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 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 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 realtime 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 coincubated 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 e 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.
