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.
Toxicol Appl Pharmacol. 2013 Oct 1;272(1):191-8. doi: 10.1016/j.taap.2013.05.023. Epub 2013 Jun 2.
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.
脱氧雪腐镰刀菌烯醇（DON）是欧洲和北美的农作物中最常见的一种单端孢霉烯族毒素。DON 通常与其他类型 B 的单端孢霉烯族毒素共存，如 3-乙酰脱氧雪腐镰刀菌烯醇（3-ADON）、15-乙酰脱氧雪腐镰刀菌烯醇（15-ADON）、雪腐镰刀菌烯醇（NIV）和呋塞米毒素-X（FX）。尽管单个霉菌毒素的细胞毒性已得到广泛研究，但霉菌毒素混合物毒性的数据有限。本研究旨在评估 B 型单端孢霉烯族毒素共同暴露对肠道上皮细胞的相互作用。增殖的 Caco-2 细胞分别单独或在二元或三元混合物中暴露于递增剂量的 B 型单端孢霉烯族毒素。MTT 试验和中性红摄取分别与线粒体和溶酶体功能相关，用于测量肠道上皮细胞的细胞毒性。五种测试的霉菌毒素对增殖肠细胞具有剂量依赖性效应，可按毒性递增顺序分类：3-ADON<15-ADON≈DON<NIV≪FX。二元或三元混合物也表现出剂量依赖性效应。在低浓度（细胞毒性效应在 10%到 30-40%之间）下，霉菌毒素组合具有协同作用；然而，DON-NIV-FX 混合物表现出拮抗作用。在较高浓度（细胞毒性效应约为 50%）下，组合具有相加或近乎相加的作用。这些结果表明，食品和饮食中低剂量霉菌毒素的同时存在可能比单独的霉菌毒素更具毒性。考虑到饮食中经常同时存在几种霉菌毒素以及消费者接触的毒素浓度，这种协同作用应该被考虑进去。
