Single-walled carbon nanotube-induced mitotic disruption
Single-walled carbon nanotube-induced mitotic disruption
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DOI：
10.1016/j.mrgentox.2011.11.017
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发表时间：
2012-06-14
影响因子：
1.9
通讯作者：
Reynolds, S. H.
中科院分区：
文献类型：
--
作者：
Sargent, L. M.;Hubbs, A. F.;Reynolds, S. H.
碳纳米管是纳米技术最早的产品之一，在医学、电子和制造业中有许多潜在的应用。碳纳米管的低密度、小尺寸和生物持久性给暴露控制和监测带来了挑战，并可能使工人呼吸道暴露。我们先前已经显示了培养的原代和永生化的人气道上皮细胞暴露于24，48和96 μ g/cm（2）的单壁碳纳米管（SWCNT）的有丝分裂纺锤体畸变。为了研究暴露工人中预期浓度下的有丝分裂纺锤体畸变，将原代和永生化人气道上皮细胞暴露于SWCNT 24 - 72 h，剂量相当于暴露20周（对于未另行规定的颗粒物，允许暴露限值）。我们现在已经证明了在这些剂量下，中心体碎片化，有丝分裂纺锤体破坏和非整倍体染色体数目。数据进一步证明多极有丝分裂纺锤体占破坏的有丝分裂的95%。多极有丝分裂纺锤体的增加与有丝分裂G2期细胞数量的增加相关，表明有丝分裂检查点反应。在暴露于0.024、0.24、2.4和24 μ g/cm（2）单壁碳纳米管的细胞中，观察到纳米管与有丝分裂纺锤体微管、中心体和浓缩染色质相关。三维重建显示中心体结构内的碳纳米管。较低的剂量不会导致细胞毒性或减少24小时后的集落形成，但是，三天后，显着的细胞毒性观察到的SWCNT暴露的细胞。集落形成试验表明，增加的增殖后7天曝光。我们的研究结果表明，在职业相关剂量的单壁碳纳米管有丝分裂纺锤体的显着中断。在碳纳米管暴露的细胞中观察到的增殖增加表明将遗传损伤传递给子细胞的可能性更大。中心体的破坏在包括肺癌在内的许多实体瘤中是常见的。由此产生的非整倍体是许多癌症进展中的早期事件，表明它可能在肿瘤发生和肿瘤进展中起作用。这些结果表明，在处理和加工碳纳米管时应谨慎。由爱思唯尔公司出版
Carbon nanotubes were among the earliest products of nanotechnology and have many potential applications in medicine, electronics, and manufacturing. The low density, small size, and biological persistence of carbon nanotubes create challenges for exposure control and monitoring and make respiratory exposures to workers likely. We have previously shown mitotic spindle aberrations in cultured primary and immortalized human airway epithelial cells exposed to 24, 48 and 96 mu g/cm(2) single-walled carbon nanotubes (SWCNT). To investigate mitotic spindle aberrations at concentrations anticipated in exposed workers, primary and immortalized human airway epithelial cells were exposed to SWCNT for 24-72 h at doses equivalent to 20 weeks of exposure at the Permissible Exposure Limit for particulates not otherwise regulated. We have now demonstrated fragmented centrosomes, disrupted mitotic spindles and aneuploid chromosome number at those doses. The data further demonstrated multipolar mitotic spindles comprised 95% of the disrupted mitoses. The increased multipolar mitotic spindles were associated with an increased number of cells in the G2 phase of mitosis, indicating a mitotic checkpoint response. Nanotubes were observed in association with mitotic spindle microtubules, the centrosomes and condensed chromatin in cells exposed to 0.024, 0.24, 2.4 and 24 mu g/cm(2) SWCNT. Three-dimensional reconstructions showed carbon nanotubes within the centrosome structure. The lower doses did not cause cytotoxicity or reduction in colony formation after 24 h; however, after three days, significant cytotoxicity was observed in the SWCNT-exposed cells. Colony formation assays showed an increased proliferation seven days after exposure. Our results show significant disruption of the mitotic spindle by SWCNT at occupationally relevant doses. The increased proliferation that was observed in carbon nanotube-exposed cells indicates a greater potential to pass the genetic damage to daughter cells. Disruption of the centrosome is common in many solid tumors including lung cancer. The resulting aneuploidy is an early event in the progression of many cancers, suggesting that it may play a role in both tumorigenesis and tumor progression. These results suggest caution should be used in the handling and processing of carbon nanotubes.. Published by Elsevier B.V.