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
Altertoxin II is an epoxide-holding perylene quinone and secondary metabolite produced by Alternaria molds.Its genotoxic potential and the high concentrations determined in laboratory fungal cultures resulted in an in...Altertoxin II is an epoxide-holding perylene quinone and secondary metabolite produced by Alternaria molds.Its genotoxic potential and the high concentrations determined in laboratory fungal cultures resulted in an increased scientific interest in this emerging contaminant.However,no natural occurrence in food has been reported to date to the best of our knowledge.Here,we unambiguously identified altertoxin II in a naturally infected,unprocessed apple.Applying a validated LC-MS/MS method,fruit peel spots(approx.1 mm in diameter),typically associated with Alternaria infestation,were tested for 17 mycotoxins produced by this genus.Negligible concentrations of tentoxin were determined 24 h after harvest,and the dibenzopyrones alternariol,alternariol monomethyl ether(AME)and AME-3-sulfate after six months of storage.Overall,these contamination patterns can be considered unlikely to be of toxicological concern for consumers.However,an inconspicuous peel lesion(0.5×1 cm)separately sampled from a stored apple,exhibited considerably high concentrations of 14 Alternaria toxins,including dibenzopyrones,their barely studied modified forms(glucosides and sulfates),as well as genotoxic perylene quinones including altertoxin II.Considering the toxicological potential of this compound,contaminations in such infected fruit parts should not be underestimated,e.g.in the case of exposure through the consumption of fresh smoothies or fruit juices.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.
文摘Altertoxin II is an epoxide-holding perylene quinone and secondary metabolite produced by Alternaria molds.Its genotoxic potential and the high concentrations determined in laboratory fungal cultures resulted in an increased scientific interest in this emerging contaminant.However,no natural occurrence in food has been reported to date to the best of our knowledge.Here,we unambiguously identified altertoxin II in a naturally infected,unprocessed apple.Applying a validated LC-MS/MS method,fruit peel spots(approx.1 mm in diameter),typically associated with Alternaria infestation,were tested for 17 mycotoxins produced by this genus.Negligible concentrations of tentoxin were determined 24 h after harvest,and the dibenzopyrones alternariol,alternariol monomethyl ether(AME)and AME-3-sulfate after six months of storage.Overall,these contamination patterns can be considered unlikely to be of toxicological concern for consumers.However,an inconspicuous peel lesion(0.5×1 cm)separately sampled from a stored apple,exhibited considerably high concentrations of 14 Alternaria toxins,including dibenzopyrones,their barely studied modified forms(glucosides and sulfates),as well as genotoxic perylene quinones including altertoxin II.Considering the toxicological potential of this compound,contaminations in such infected fruit parts should not be underestimated,e.g.in the case of exposure through the consumption of fresh smoothies or fruit juices.
