Induction of genotoxic effects and modulation of the intracellular calcium level in syrian hamster embryo (SHE) fibroblasts caused by ochratoxin A
Induction of genotoxic effects and modulation of the intracellular calcium level in syrian hamster embryo (SHE) fibroblasts caused by ochratoxin A
复制标题
DOI：
10.1016/s0278-6915(99)00057-5
复制
发表时间：
1999-07-01
影响因子：
4.3
通讯作者：
Schiffmann, D
中科院分区：
文献类型：
--
作者：
Dopp, E;M端ller, J;Schiffmann, D
真菌毒素赭曲霉毒素A(OTA)是一种天然存在的食品污染物。OTA的遗传毒性仍然存在争议，因为在各种微生物和哺乳动物的基因突变检测中得到了相互矛盾的结果。在本研究中，研究了OTA对SHE细胞微核(MN)的诱导作用。SHE-微核试验显示OTA以剂量和时间依赖的方式诱导MN。动粒分析结果表明，OTA的遗传毒性主要涉及碎裂事件。有丝分裂障碍的诱导与细胞内钙离子浓度([Ca~(2+)](I))的变化密切相关。对OTA引起的[Ca~(2+)](I)变化的时间进程的研究表明，所获得的信号是类似生理反应的短脉冲信号。在没有细胞外钙的情况下，一个长期的信号表明细胞内的钙储存或通道可能受到损害。我们的数据表明，OTA诱导的[Ca~(2+)](I)升高是由细胞内钙释放和细胞外钙内流引起的。最后，研究了细胞内钙离子水平的变化对肌动蛋白细胞骨架的影响。肌动蛋白细丝的可视化显示出时间和浓度依赖的效应。细胞收缩，纤维解聚。我们得出结论，OTA通过与肌动蛋白的直接不可逆结合来破坏肌动蛋白细丝。(C)1999爱思唯尔科学有限公司。保留所有权利。
The mycotoxin ochratoxin A (OTA) is a naturally occuring contaminant of food. The genotoxic status of OTA is still controversial because contradictory results were obtained in various microbial and mammalian gene mutation assays. In this study, OTA was investigated to examine its potency to induce micronuclei (MN) in SHE cells. The SHE-micronucleus assay revealed that OTA induces MN in a dose- and time-dependent manner. The results of kinetochore analysis revealed that mainly clastogenic events are involved in OTA genotoxicity. Induction of mitotic disturbances can be closely related to changes of the intracellular calcium concentration ([Ca2+](i)). The investigated time course of OTA-induced [Ca2+](i) changes revealed that the obtained signal is a short spike signal resembling physiological responses. In the absence of extracellular calcium, a long-lasting signal indicates possible damage to intracellular calcium stores or channels. Our data show that the OTA-induced [Ca2+](i) rise is caused by Ca2+-release from intracellular stores as well as Ca2+ influx from extracellular area. Finally, the influence of the changed intracellular calcium level on the actin cytoskeleton was investigated. Visualization of the actin filaments revealed time- and concentration-dependent effects. Cell shrinkage and depolymerized filaments were observed. We conclude that OTA disrupts actin filaments by a direct irreversible binding to actin. (C) 1999 Elsevier Science Ltd. All rights reserved.