排序方式: 共有3条查询结果,搜索用时 0 毫秒
1
1.
Maricica Pacurari Diane Schwegler-Berry Sherri Friend Steven S. Leonard Robert R. Mercer Val Vallyathan 《毒物与环境化学》2013,95(5):1045-1072
Single-walled carbon nanotubes (SWCNT) are being developed to be used in many industrial and biomedical applications. However, SWCNT's durability and likely fibrous morphology have raised health concerns. The present investigations were focused on understanding the cellular and molecular mechanisms induced by raw SWCNT (SWCNT) in human bronchial-epithelial cells (BEAS-2B). Asbestos (crocidolite) was used as a positive control. Exposure of BEAS-2B cells to SWCNT induced apoptosis, DNA damage, and oxidative stress. The generation of hydroxyl radical (?OH) and increase of superoxide dismutase (SOD) activity were concentration-dependent. The increase in apoptosis was associated with activation of caspase-3, caspase-7, and poly (ADP-ribose) polymerase-1 (PARP-1). A short recovery period of 6?h of cells from SWCNT exposure resulted in reversal of caspase-3 and caspase-7, and a partial reversal of PARP-1 activation. The activation of PARP-1, caspase-3, and caspase-7 was only partially diminished after a recovery of 6?h from the exposure to crocidolite. Exposure of BEAS-2B cells to SWCNT resulted in the phosphorylation of protein p42/44 (p42/44) and protein p38 (p38). SWCNT did not induce protein serine-threonine kinase (AKT) phosphorylation. For all the above end points, crocidolite induced a greater response compared to SWCNT. SWCNT induced a significant activation of activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB), and the effect was inhibited by mitogen-activated protein kinase (MAPK) inhibitors. SWCNT also induced significant increase in the expression levels of c-Jun, βIGH3, and CD44 genes. The results of this study show that the molecular mechanism for raw SWCNT-mediated toxicity in BEAS-2B cells is through the activation of caspase-3, caspase-7, and PARP-1. Furthermore, the mechanism of AP-1 and NF-κB activation is through MAPK. This bioactivity of raw SWCNT is associated with the generation of oxidative stress and DNA damage. Considering the role of airway epithelium as a critical barrier for normal pulmonary function and focal point for tumor development, this study demonstrates that raw SWCNT activate molecular events which may be linked to adverse biological responses implicated in pulmonary diseases. 相似文献
2.
3.
Wes Gibbons 《Environmental geochemistry and health》1998,20(4):213-230
The risk to human health associated with the inhalation of amphibole asbestos has become devastatingly ap- parent this century. The most commonly utilised asbestiform amphiboles, crocidolite (blue asbestos) and amosite (brown asbestos), are implicated in a variety of diseases related to cell damage within the respiratory tract and adjacent areas. Blue and brown asbestos fibres have a morphology and mineralogy which makes them more biopersistent and biochemically reactive than chrysotile (white asbestos). The long-term pres- ence of such fibres within and around the lungs can result in fibrous scarring, lung cancer, and is the major cause of the once extremely rare tumour known as diffuse malignant mesothelioma. Therefore, despite the fact that asbestiformamphiboles comprise approximately 5%of industrially utilised asbestos (the rest being chrysotile), they have been disproportionately pathogenic. Almost all amphibole asbestos sold on the world market was mined from Palaeoproterozoic ironstones in either the northern Cape Province (blue) or Trans- vaal (brown and blue) areas in South Africa. Production peaked from 1966–1978 when around 2 million tons of crocidolite and1million tons of amosite were produced and exported to be used mainly in asbestos-based cement products and many types of building materials. Crocidolite mixed with chrysotile was commonly used in pressure pipes and gaskets, whereas amosite mixed with chrysotile was especially suitable for gut- ters, roofing, and insulation boards. Amid- to late 20th century amphibole asbestos-related cancer epidemic has consequently struck not only mining and milling communities in producer countries, but many groups of workers (and their relatives and neighbours) exposed to amphibole asbestos-bearing materials in importer countries. Although belated closure and reparation of the mines and imposition of threshold safety limits in the workplace will eventually stem this epidemic the death toll has not yet peaked. Given the long latency period (decades) typical of mesothelioma and bronchogenic carcinoma and the fact that amphibole asbes- tos-bearing materials are still present in some buildings, asbestos-related cancer will inevitably continue to be a major cause of death in many countries worldwide well into the next century. 相似文献
1