title: Modulation of the cellular redox status by the Alternaria toxins alternariol and alternariol monomethyl ether.
abstract: The mycotoxin alternariol (AOH) has been reported to possess genotoxic properties, inducing enhanced levels of DNA damage after only 1 h of incubation. In the present study we addressed the question whether the induction of oxidative stress might contribute to the genotoxic effects of AOH or its naturally occurring monomethylether (AME). In the dichlorofluorescein (DCF) assay, treatment of HT29 cells for 1 h enhanced the formation of dichlorofluorescein, indicative for ROS formation. The total glutathione (tGSH) was transiently decreased. In accordance with the results of the DCF assay, AOH and AME enhanced the proportion of the transcription factor Nrf2 in the nucleus. Concomitantly, the Nrf2/ARE-dependent genes γ-glutamylcysteine ligase (γ-GCL) and glutathione-S-transferase (GSTA1/2) showed enhanced transcript levels. After 24 h of incubation this effect was also reflected on the protein level by an increase of GST activity. However, in spite of the positive DCF assay and the activation of the redox-sensitive Nrf2/ARE-pathway, the level of oxidative DNA damage, measured in the comet assay by the addition of formamidopyrimidine-DNA-glycosylase (fpg) remained unaffected. Of note, after 3 h of incubation no significant DNA damaging potential of AOH and AME was detectable, indicating either inactivation of the compounds or enhanced DNA repair. In summary, the mycotoxins AOH and AME were found to modulate the redox balance of HT29 cells but without apparent negative effect on DNA integrity.
authors.affiliation: University of Vienna, Department of Food Chemistry and Toxicology, Waehringer Str. 38, A-1090 Vienna, Austria.
authors.forename: Christine
authors.initials: C
authors.lastname: Tiessen
authors.forename: Markus
authors.initials: M
authors.lastname: Fehr
authors.forename: Christoph
authors.initials: C
authors.lastname: Schwarz
authors.forename: Simone
authors.initials: S
authors.lastname: Baechler
authors.forename: Katharina
authors.initials: K
authors.lastname: Domnanich
authors.forename: Ute
authors.initials: U
authors.lastname: Böttler
authors.forename: Gudrun
authors.initials: G
authors.lastname: Pahlke
authors.forename: Doris
authors.initials: D
authors.lastname: Marko
mesh_terms: D000528:Alternaria / Q000737:chemistry*; D020552:Comet Assay; D016895:Culture Media, Serum-Free; D004249:DNA Damage / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000633:toxicity*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D015394:Molecular Structure; D009183:Mycotoxins / Q000737:chemistry / Q000633:toxicity*; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress
chemical_list: D016895:Culture Media, Serum-Free; D007783:Lactones; D009183:Mycotoxins; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D005978:Glutathione; C005197:alternariol; C018206:alternariol monomethyl ether