中文摘要：霉菌毒素是由各种真菌形成的有毒次生代谢产物，是天然的食物污染物。这些不同种类的化合物会引发多种毒性机制，包括干扰内分泌。就大多数化学物质而言，目前对霉菌毒素风险的评估，与大多数化学物质一样，都基于单一化合物的作用。然而，近年来对天然混合物中因单一物质间相互作用而可能增强风险的担忧大大增加。本文详细研究了三种霉菌性雌激素的组合作用，包括镰刀菌产生的玉米赤霉烯酮（ZEN）和α-玉米赤霉烯醇（α-ZEL）及链格孢产生的具有细胞毒性及雌激素作用的霉菌毒素链格孢酚(AOH)等内分泌干扰物。为了评估组合作用，在腺癌细胞系Ishikawa中测试了碱性磷酸酶（AlP）的雌激素依赖性活化和细胞增殖。
研究发现三种真菌毒素都可作为部分激动剂。大多数二元组合，即使在α-ZEL的浓度非常低的情况下，也在AlP测定中显示出很强的协同作用。霉菌毒素混合物的这些增强现象强调了迫切需要将组合效应纳入未来的风险评估，特别是涉及内分泌干扰物时。据悉，本文研究真菌类雌激素的协同效应尚属首次。
外文摘要： Mycotoxins are toxic secondary metabolites formed by various fungal species that are found as natural contaminants in food. This very heterogeneous group of compounds triggers multiple toxic mechanisms, including endocrine disruptive potential. Current risk assessment of mycotoxins, as for most chemical substances, is based on the effects of single compounds. However, concern on a potential enhancement of risks by interactions of single substances in naturally occurring mixtures has greatly increased recently. In this study, the combinatory effects of three mycoestrogens were investigated in detail. This includes the endocrine disruptors zearalenone (ZEN) and α-zearalenol (α-ZEL) produced by Fusarium fungi and alternariol (AOH), a cytotoxic and estrogenic mycotoxin formed by Alternaria species. For evaluation of effects, estrogen-dependent activation of alkaline phosphatase (AlP) and cell proliferation were tested in the adenocarcinoma cell line Ishikawa. The estrogenic potential varied among the single substances. Half maximum effect concentrations (EC50) for AlP activation were evaluated for α-ZEL, ZEN and AOH as 37 pM, 562 pM and 995 nM, respectively. All three mycotoxins were found to act as partial agonists. The majority of binary combinations, even at very low concentrations in the case of α-ZEL, showed strong synergism in the AlP assay. These potentiating phenomena of mycotoxin mixtures highlight the urgent need to incorporate combinatory effects into future risk assessment, especially when endocrine disruptors are involved. To the best of our knowledge, this study presents the first investigation on synergistic effects of mycoestrogens.
外文关键词：Xenoestrogen；Natural toxin；Food safety；Food contaminants；Chemical mixtures
作者：Vejdovszky, K；Hahn, K；Braun, D；Warth, B；Marko, D
作者单位：Univ Vienna
期刊名称：ARCHIVES OF TOXICOLOGY
期刊影响因子：6.637
出版年份：2017
出版刊次：3
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