title: New insights into mycotoxin mixtures: the toxicity of low doses of Type B trichothecenes on intestinal epithelial cells is synergistic.
abstract: Deoxynivalenol (DON) is the most prevalent trichothecene mycotoxin in crops in Europe and North America. DON is often present with other type B trichothecenes such as 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), nivalenol (NIV) and fusarenon-X (FX). Although the cytotoxicity of individual mycotoxins has been widely studied, data on the toxicity of mycotoxin mixtures are limited. The aim of this study was to assess interactions caused by co-exposure to Type B trichothecenes on intestinal epithelial cells. Proliferating Caco-2 cells were exposed to increasing doses of Type B trichothecenes, alone or in binary or ternary mixtures. The MTT test and neutral red uptake, respectively linked to mitochondrial and lysosomal functions, were used to measure intestinal epithelial cytotoxicity. The five tested mycotoxins had a dose-dependent effect on proliferating enterocytes and could be classified in increasing order of toxicity: 3-ADON<15-ADON≈DON<NIV≪FX. Binary or ternary mixtures also showed a dose-dependent effect. At low concentrations (cytotoxic effect between 10 and 30-40%), mycotoxin combinations were synergistic; however DON-NIV-FX mixture showed antagonism. At higher concentrations (cytotoxic effect around 50%), the combinations had an additive or nearly additive effect. These results indicate that the simultaneous presence of low doses of mycotoxins in food commodities and diet may be more toxic than predicted from the mycotoxins alone. Considering the frequent co-occurrence of trichothecenes in the diet and the concentrations of toxins to which consumers are exposed, this synergy should be taken into account.
authors.affiliation: INRA, UMR 1331 Toxalim, Research Center in Food Toxicology, F-31027 Toulouse, France; Université de Toulouse, ENVT, INP, UMR 1331 Toxalim, F-31076 Toulouse, France; Institut des Sciences Biomédicales Appliquées, Cotonou, Bénin.
authors.forename: Imourana
authors.initials: I
authors.lastname: Alassane-Kpembi
authors.forename: Martine
authors.initials: M
authors.lastname: Kolf-Clauw
authors.forename: Thierry
authors.initials: T
authors.lastname: Gauthier
authors.forename: Roberta
authors.initials: R
authors.lastname: Abrami
authors.forename: François A
authors.initials: FA
authors.lastname: Abiola
authors.forename: Isabelle P
authors.initials: IP
authors.lastname: Oswald
authors.forename: Olivier
authors.initials: O
authors.lastname: Puel
mesh_terms: D000465:Algorithms; D018938:Caco-2 Cells; D002470:Cell Survival / Q000187:drug effects; D004396:Coloring Agents; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology* / Q000187:drug effects*; D009183:Mycotoxins / Q000633:toxicity*; D013778:Tetrazolium Salts; D013844:Thiazoles; D014255:Trichothecenes / Q000633:toxicity*
chemical_list: D004396:Coloring Agents; D009183:Mycotoxins; D013778:Tetrazolium Salts; D013844:Thiazoles; D014255:Trichothecenes; C002469:fusarenon-X; C043247:3-acetyldeoxynivalenol; C038405:nivalenol; C046760:15-acetyldeoxynivalenol; C022616:thiazolyl blue; C007262:deoxynivalenol
keywords: 15-ADON; 15-acetyldeoxynivalenol; 3,(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide; 3-ADON; 3-acetyldeoxynivalenol; CI; Combination index; Cytotoxicity; DON; DRI; Dose reduction index; FX; IC(50); MTT; Mycotoxin; NIV; Synergy; Trichothecenes; combination index; deoxynivalenol; dose reduction index; f(a); fraction affected; fusarenon-X; inhibitory concentration 50%; nivalenol