title: Non-synergistic cytotoxic effects of Fusarium and Alternaria toxin combinations in Caco-2 cells.
abstract: Exposure of humans and animals to mycotoxins via food and feed generally involves a conglomeration of compounds contaminating the consumed products. Investigations on combinatory effects of mycotoxins are therefore of great importance. In this study, cytotoxic effects of binary mixtures of the Fusarium toxins enniatin B, aurofusarin, deoxynivalenol, nivalenol and zearalenone, and tenuazonic acid produced by Alternaria spp., were evaluated by the WST-1 assay in the colorectal carcinoma cell-line Caco-2 after 24h of incubation. The selection of these mycotoxins was based on typically occurring natural contamination patterns in grains. Aurofusarin, which can be found abundantly in contaminated foodstuff and has not been toxicologically characterized properly so far, showed pronounced cytotoxicity, decreasing the mitochondrial activity at 10μM to 51% compared to a solvent control. Combinations of other mycotoxins with aurofusarin showed additive effects. In contrast, binary mixtures of enniatin B, deoxynivalenol, nivalenol and zearalenone at cytotoxic concentrations, predominantly resulted in antagonistic effects. Binary combinations of these four Fusarium toxins with tenuazonic acid also revealed interacting effects leading to a decrease in cytotoxicity, compared to expected combinatory effects. Especially in combination with deoxynivalenol, tenuazonic acid was found to significantly reduce the cytotoxicity of this mycotoxin in Caco-2 cells. Synergistic effects were not observed for any toxin combination under the chosen conditions.
authors.affiliation: University of Vienna, 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, Department of Food Chemistry and Toxicology, Waehringer Str. 38, A-1090 Vienna, Austria.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Warth
authors.affiliation: Center for Analytical Chemistry, Department for Agrobiotechnology (IFA-Tulln), University of Natural Resources and Life Sciences, Vienna (BOKU), Konrad-Lorenz-Str. 20, Vienna, A-3430 Tulln, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Sulyok
authors.affiliation: University of Vienna, 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: D000465:Algorithms; D000528:Alternaria / Q000737:chemistry*; D018938:Caco-2 Cells; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D002523:Edible Grain / Q000737:chemistry; D005506:Food Contamination / Q000032:analysis; D005670:Fusarium / Q000737:chemistry*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009183:Mycotoxins / Q000633:toxicity*
chemical_list: D009183:Mycotoxins
keywords: Antagonism; Caco-2; Combinatory effects; Food contaminants; Mycotoxins; WST-1 assay