Bergamini C, Fato R, Biagini G, Pugnaloni A, Giantomassi F, Foresti E, Lesci G I, Roveri N, Lenaz G
Department of Biochemistry G. Moruzzi, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
Cell Mol Biol (Noisy-le-grand). 2007 Jan 21;52 Suppl:OL905-13.
Asbestos fibers, such as chrysotile and crocidolite, are known to have cytotoxic effects on different cell types. In vivo exposure to asbestos fibers can induce both fibrotic and malignant lung diseases , however, the mechanisms linking exposure to the subsequent development of the diseases are unknown. Numerous investigations suggest the involvement of reactive oxygen species (ROS). ROS are known to damage biological macromolecules including proteins, cell membrane lipids and nucleic acids; alterations of these essential cellular components can alter cell function and can drive the cell to neoplastic transformation or to cell death. Because the mitochondrial respiratory chain is an important source of ROS and RNS (reactive nitogen species) in the cells, we have investigated the effects of aqueous extracts of asbestos (natural and synthetic) fibers on some mitochondrial activities. Our data show that crocidolite fibers release substances in solution that may interfere directly with the mitochondrial cytochrome oxidase complex. Moreover, the calcium ions released from these fibers induce opening of the permeability transition pore of the inner membrane leading to a possible cytotoxic effect due to the release of apoptotic factors normally localized in the mitochondrial intermembrane space. In addition, crocidolite extracts enhance the mitochondrial production of ROS. No significant biochemical effects are exerted by chrysotile, either natural or synthetic, on isolated mitochondria. Nevertheless, all asbestos fibers tested induce morphological alterations visualized by transmission electron microscopy and morphometric analysis.
温石棉和青石棉等石棉纤维对不同细胞类型具有细胞毒性作用。体内暴露于石棉纤维可诱发肺纤维化和恶性肺病，然而，暴露与后续疾病发展之间的关联机制尚不清楚。大量研究表明活性氧（ROS）参与其中。已知ROS会损害包括蛋白质、细胞膜脂质和核酸在内的生物大分子；这些重要细胞成分的改变会改变细胞功能，并可促使细胞发生肿瘤转化或细胞死亡。由于线粒体呼吸链是细胞内ROS和活性氮（RNS）的重要来源，我们研究了石棉（天然和合成）纤维水提取物对某些线粒体活性的影响。我们的数据表明，青石棉纤维在溶液中释放的物质可能直接干扰线粒体细胞色素氧化酶复合物。此外，从这些纤维中释放的钙离子会诱导内膜通透性转换孔开放，由于通常位于线粒体内膜间隙的凋亡因子释放，可能导致细胞毒性作用。此外，青石棉提取物会增强线粒体ROS的产生。天然或合成温石棉对分离的线粒体均未产生明显的生化影响。然而，所有测试的石棉纤维均会诱导形态学改变，这可通过透射电子显微镜和形态计量分析观察到。
