title: In vitro combinatory effects of the Alternaria mycotoxins alternariol and altertoxin II and potentially involved miRNAs.
abstract: Alternariol (AOH) and altertoxin II (ATX II) are mycotoxins formed by Alternaria spp. Since they are expected to co-occur in Alternaria-infested food and feed, we addressed the question of combinatory effects. In addition, potentially involved regulatory microRNAs were surveyed in an exploratory approach. Cytotoxicity measurements in constant ratio combinations of 1:10 or 1:1 (ATX II: AOH) mainly revealed additive effects in HepG2, HT29 and HCEC-1CT cells. Yet, in specific high doses antagonism was found. Microarray analysis of miRNA expression profiles in HepG2 cells indicated different patterns of miRNA regulation by AOH and ATX II, including several miRNA species for which no distinct functions are currently known. Among others, miR-4654, miR-4715_3p and miR-6720_3p were up-regulated by AOH and miR-5583_5p was down-regulated by ATX II. Additionally, miR-1323, involved in hindering DNA repair mechanisms, was decreased by ATX II. Digital droplet PCR (ddPCR) analysis of selected miRNAs indicated regulation of miR-29a by AOH, which might play a role in AOH-induced apoptosis. miR-192 and miR-224 regulation was associated with antagonistic cytotoxic effects of AOH and ATX II combinations. Our study represents the first evaluation on combinatory effects of AOH and ATX II.
authors.affiliation: University of Vienna, Faculty of Chemistry, Department of Food Chemistry and Toxicology, Waehringer Str. 38, A-1090 Vienna, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Vejdovszky
authors.affiliation: University of Vienna, Faculty of Chemistry, Department of Inorganic Chemistry, Althanstrasse 14, A-1090 Vienna, Austria.
authors.forename: Matej
authors.initials: M
authors.lastname: Sack
authors.affiliation: University of Vienna, Faculty of Chemistry, Department of Food Chemistry and Toxicology, Waehringer Str. 38, A-1090 Vienna, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Jarolim
authors.affiliation: University of Vienna, Faculty of Chemistry, Department of Food Chemistry and Toxicology, Waehringer Str. 38, A-1090 Vienna, Austria.
authors.forename: Georg
authors.initials: G
authors.lastname: Aichinger
authors.affiliation: University of Vienna, Faculty of Chemistry, Department of Inorganic Chemistry, Althanstrasse 14, A-1090 Vienna, Austria.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Somoza
authors.affiliation: University of Vienna, Faculty of Chemistry, Department of Food Chemistry and Toxicology, Waehringer Str. 38, A-1090 Vienna, Austria. Electronic address: doris.marko@univie.ac.at.
authors.forename: Doris
authors.initials: D
authors.lastname: Marko
mesh_terms: D000528:Alternaria / Q000378:metabolism*; D001551:Benz(a)Anthracenes / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005506:Food Contamination; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D019073:HT29 Cells; D056945:Hep G2 Cells; D006801:Humans; D007783:Lactones / Q000633:toxicity*; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction
chemical_list: D001551:Benz(a)Anthracenes; D007783:Lactones; C546783:MIRN192 microRNA, human; C546140:MIRN224 microRNA, human; D035683:MicroRNAs; C050234:altertoxin II; C005197:alternariol
keywords: Alternaria alternata; Chemical mixtures; Cytotoxicity; Mycotoxins; ddPCR; miRNA