A cochlear cell line as an in vitro system for drug ototoxicity screening

A cochlear cell line as an in vitro system for drug ototoxicity screening
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DOI:
10.1159/000071059
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发表时间:
2003-07-01
影响因子:
1.6
通讯作者:
Kalinec, F
Kalinec, F
中科院分区:
医学3区
文献类型:
--
作者:
Kalinec, GM;Webster, P;Kalinec, F

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氨基糖苷类抗生素、髓袢利尿剂、利尿剂等常用药理学药物具有耳毒性。然而,由于内耳组织的有限可用性和药物对实验动物的副作用,对药物耳毒性的细胞和分子机制的理解受到阻碍。来自听觉感觉器官的永生细胞系,对耳毒性药物敏感,并在可以系统操纵的环境中生长,将促进旨在阐明这些机制的研究。这种永生化细胞系也可用于发现预防药物诱导的感音神经性听力损失的新型治疗剂。在这里,我们报告了一个条件永生化的器官Corti衍生的上皮细胞系,这表明细胞凋亡的激活证据时,暴露于已知的耳毒性药物。该细胞系可能是研究耳毒性的细胞和分子机制以及筛选潜在的耳毒性或耳保护特性的新药理学药物的极好的体外系统。版权所有(C)2003 S. Karger AG,巴塞尔。
Aminoglycoside antibiotics, loop diuretics, antineoplastic agents and other commonly used pharmacological drugs are ototoxic. Understanding of the cellular and molecular mechanisms underlying drug ototoxicity, however, has been hampered by the limited availability of inner ear tissues and drug side effects on laboratory animals. Immortalized cell lines derived from the auditory sensory organ, sensitive to ototoxic drugs and growing in environments that can be systematically manipulated, would facilitate the research directed at elucidating these mechanisms. Such immortalized cell lines could also be used to discover novel therapeutic agents for preventing drug-induced sensorineural hearing loss. Here, we report a conditionally immortalized organ of Corti-derived epithelial cell line, which shows evidence of activation of apoptosis when exposed to known ototoxic drugs. This cell line may be an excellent in vitro system to investigate the cellular and molecular mechanisms involved in ototoxicity and for screening of the potential ototoxicity or otoprotective properties of new pharmacological drugs. Copyright (C) 2003 S. Karger AG, Basel.