Unraveling the mechanisms involved in zearalenone-mediated toxicity in permanent fish cell cultures
Unraveling the mechanisms involved in zearalenone-mediated toxicity in permanent fish cell cultures
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DOI：
10.1016/j.toxicon.2014.06.005
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发表时间：
2014-09-15
期刊：
影响因子：
2.8
通讯作者：
Burkhardt-Holm, Patricia
中科院分区：
文献类型：
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作者：
Pietsch, Constanze;Noser, Juerg;Burkhardt-Holm, Patricia
玉米赤霉烯酮（ZEN）作为一种污染物在世界范围内广泛存在于农场动物和鱼类饲料中，需要对ZEN的毒性作用机制进行评价。本研究调查了ZEN在鱼细胞系中可能的代谢，表明主要发生葡萄糖醛酸化。研究表明，高达20,000 ng ml（-1）的ZEN浓度能够以剂量-反应方式影响永久性鱼细胞培养中的细胞活力，在五种测试细胞系之间具有不同的反应模式，其中溶酶体似乎是ZEN的主要目标。ZEN毒性经常在氧化应激的背景下被讨论。我们的研究表明，当监测活性氧（ROS）的产生时，细胞系的双相反应。通过测量脂质过氧化、DNA链断裂和细胞内谷胱甘肽水平的改变来观察细胞损伤。ZEN的代谢，特别是在浓度超过7500 ng ml(-1) ZEN时，不能阻止细胞毒性。ZEN作为一种雌激素化合物可能涉及与雌激素受体（ER）结合介导的过程。由于一种细胞系没有检测到内质网的表达，内质网介导的途径似乎不太可能在这些细胞中出现。这证实了溶酶体途径是鱼细胞中ZEN的主要靶点。(C) 2014 Elsevier Ltd.版权所有。
The world-wide occurrence of zearalenone (ZEN) as a contaminant in feed for farm animals and fish requires the evaluation of toxicity mechanisms of action of ZEN. The present study investigates possible metabolization of ZEN in fish cell lines suggesting that mainly glucuronidation takes place. It demonstrates that concentrations up to 20,000 ng ml(-1) ZEN are capable of influencing cell viability in permanent fish cell cultures in a dose-response manner with different response patterns between the five tested cell lines, whereby lysosomes appeared to be the main target of ZEN. ZEN toxicity is often discussed in the context of oxidative stress. Our study shows a biphasic response of the cell lines when reactive oxygen species (ROS) production is monitored. Damage in cells was observed by measuring lipid peroxidation, DNA strand breaks, and alterations of intracellular glutathione levels. Metabolization of ZEN, especially at concentrations above 7500 ng ml(-1) ZEN, does not prevent cytotoxicity. ZEN as an estrogenic compound may involve processes mediated by binding to estrogen receptors (ER). Since one cell line showed no detectable expression of ER, an ER-mediated pathway seems to be unlikely in these cells. This confirms a lysosomal pathway as a main target of ZEN in fish cells. (C) 2014 Elsevier Ltd. All rights reserved.