Toxicity and carcinogenicity mechanisms of fibrous antigorite.

Toxicity and carcinogenicity mechanisms of fibrous antigorite.
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DOI:
10.3390/ijerph2007010001
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发表时间:
2007-03-01
影响因子:
--
通讯作者:
Balazy, Michael
Balazy, Michael
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Cardile, Venera;Lombardo, Laura;Balazy, Michael

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我们研究了纤维叶蛇纹石对间皮细胞MeT-5A和单核巨噬细胞J774细胞系的影响,以进一步了解石棉纤维诱导的肺损伤和癌症的细胞机制。叶蛇纹石是一种具有石棉性质的矿物,往往与温石棉或透闪石伴生,经常作为主要矿物出现在西阿尔卑斯山丰富发现的几种蛇纹岩的脉中。含叶蛇纹石的颗粒在该地区的呼吸空气中比通常在城市环境空气中发现的颗粒更丰富。将MeT-5A和J774细胞暴露于浓度为5-100 μ g/ml的纤维叶蛇纹石72小时诱导剂量依赖性细胞毒性。叶蛇纹石还刺激ROS的产生,诱导亚硝酸盐和PGE 2的产生。MeT-5A细胞对叶蛇纹石的敏感性高于J774细胞。本研究的结果显示,纤维叶蛇纹石刺激环氧合酶和羟基和一氧化氮自由基的形成。这些变化代表了叶蛇纹石纤维的早期细胞反应,其导致许多病理和肿瘤状况,因为自由基和PGE 2作为肿瘤发病机制的介质发挥重要作用。了解叶蛇纹石和其他石棉颗粒的细胞反应机制,应有助于设计合理的预防和治疗方法。
We studied the effects of fibrous antigorite on mesothelial MeT-5A and monocyte-macrophage J774 cell lines to further understand cellular mechanisms induced by asbestos fibers leading to lung damage and cancer. Antigorite is a mineral with asbestiform properties, which tends to associate with chrysotile or tremolite, and frequently occurs as the predominant mineral in the veins of several serpentinite rocks found abundantly in the Western Alps. Particles containing antigorite are more abundant in the breathing air of this region than those typically found in urban ambient air. Exposure of MeT-5A and J774 cells to fibrous antigorite at concentrations of 5-100 microg/ml for 72 hr induced dose-dependent cytotoxicity. Antigorite also stimulated the ROS production, induced the generation of nitrite and PGE2. MeT-5A cells were more sensitive to antigorite than J774 cells. The results of this study revealed that the fibrous antigorite stimulates cyclooxygenase and formation of hydroxyl and nitric oxide radicals. These changes represent early cellular responses to antigorite fibers, which lead to a host of pathological and neoplastic conditions because free radicals and PGE2 play important roles as mediators of tumor pathogenesis. Understanding the mechanisms of the cellular responses to antigorite and other asbestos particles should be helpful in designing rational prevention and treatment approaches.