Vejdovszky Katharina, Sack Matej, Jarolim Katharina, Aichinger Georg, Somoza Mark M, Marko Doris
University of Vienna, Faculty of Chemistry, Department of Food Chemistry and Toxicology, Waehringer Str. 38, A-1090 Vienna, Austria.
University of Vienna, Faculty of Chemistry, Department of Inorganic Chemistry, Althanstrasse 14, A-1090 Vienna, Austria.
Toxicol Lett. 2017 Feb 5;267:45-52. doi: 10.1016/j.toxlet.2016.12.011. Epub 2016 Dec 19.
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.
链格孢酚（AOH）和互隔交链孢酚毒素II（ATX II）是链格孢属真菌产生的霉菌毒素。由于预计它们会同时出现在受链格孢属真菌污染的食品和饲料中，我们研究了它们的联合作用问题。此外，还以探索性的方式对可能涉及的调控微小RNA进行了研究。对1:10或1:1（ATX II:AOH）恒定比例组合的细胞毒性测量结果表明，在HepG2、HT29和HCEC-1CT细胞中主要呈现相加作用。然而，在特定高剂量下发现了拮抗作用。对HepG2细胞中微小RNA表达谱的微阵列分析表明，AOH和ATX II对微小RNA的调控模式不同，包括几种目前尚无明确功能的微小RNA。其中，miR-4654、miR-4715_3p和miR-6720_3p被AOH上调，miR-5583_5p被ATX II下调。此外，参与阻碍DNA修复机制的miR-1323被ATX II降低。对选定微小RNA的数字液滴PCR（ddPCR）分析表明，AOH对miR-29a有调控作用，这可能在AOH诱导的细胞凋亡中发挥作用。miR-192和miR-224的调控与AOH和ATX II组合的拮抗细胞毒性作用有关。我们的研究是对AOH和ATX II联合作用的首次评估。
