Mineral fibers induce apoptosis in syrian hamster embryo fibroblasts
Mineral fibers induce apoptosis in syrian hamster embryo fibroblasts
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DOI：
10.1159/000163954
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发表时间：
1995-07-01
期刊：
影响因子：
5
通讯作者：
Schiffmann, D
中科院分区：
文献类型：
--
作者：
Dopp, E;Nebe, B;Schiffmann, D
众所周知，石棉和其他矿物纤维会诱发肺癌和间皮瘤。然而，纤维诱导癌变的主要机制仍有待阐明。先前的研究，包括我们自己的研究，已经表明石棉引起特定的有丝分裂干扰，微核形成和典型的染色质结构变化，类似于细胞凋亡。这种效应被认为是程序性细胞死亡，移除受损或癌前细胞。我们研究了石棉（石棉、青石棉、温石棉）和陶瓷纤维对细胞凋亡的诱导作用。凝胶电泳鉴定DNA片段呈典型阶梯状，测定细胞内钙浓度，流式细胞术测定凋亡细胞百分比。不同纤维对叙利亚仓鼠胚胎（SHE）细胞凋亡的诱导作用不同。根据纤维类型的不同，3-33%的细胞发生凋亡。温石棉是诱导细胞凋亡最有效的纤维。此外，凋亡的SHE细胞细胞内钙水平升高。温石棉在暴露时间（66-72小时）明显长于顺铂（24小时）后诱导细胞凋亡。鉴于这些发现，我们假设温石棉诱导细胞凋亡是由于细胞内调节途径的长期变化。
It is known that asbestos and other mineral fibers induce lung cancer and mesothelioma. However, the primary mechanisms of fiber-induced carcinogenesis still remain to be elucidated. Previous studies, including our own, have shown that asbestos causes specific mitotic disturbances, micronucleus formation and typical changes in chromatin structure resembling those of apoptosis. This effect has been considered as programmed cell death removing damaged or pre-cancerous cells. We investigated the induction of apoptosis by asbestos (amosite, crocidolite, chrysotile) and ceramic fibers. The typical ladder pattern of DNA fragments was identified by means of gel electrophoresis, the intracellular calcium concentration was measured and flow cytometry analyses were carried out to determine the percentage of apoptotic cells. The different fibers showed different potencies for the induction of apoptosis in Syrian hamster embryo (SHE) cells. Depending on the type of fiber applied 3-33% of cells underwent apoptosis. Chrysotile proved to be the most potent inducer of apoptosis compared to the other fibers. In addition, an increased intracellular calcium level was observed in apoptotic SHE cells. Chrysotile induced apoptosis after a considerably longer exposure time (66-72 h) than cisplatin (24 h). In view of these findings we hypothesize that chrysotile induces apoptosis resulting from long-term changes in intracellular regulation pathways.