Department of Molecular Science and Technology, Ajou University, Suwon, Korea.
PLoS One. 2011;6(10):e25892. doi: 10.1371/journal.pone.0025892. Epub 2011 Oct 7.
The toxicological studies on carbon nanotubes (CNTs) have been urgently needed from the emerging diverse applications of CNTs. Physicochemical properties such as shape, diameter, conductance, surface charge and surface chemistry of CNTs gained during manufacturing processes play a key role in the toxicity. In this study, we separated the semi-conductive components of SWCNTs (semi-SWCNTs) and evaluated the toxicity on days 1, 7, 14 and 28 after intratracheal instillation in order to determine the role of conductance. Exposure to semi-SWCNTs significantly increased the growth of mice and significantly decreased the relative ratio of brain weight to body weight. Recruitment of monocytes into the bloodstream increased in a time-dependent manner, and significant hematological changes were observed 28 days after exposure. In the bronchoalveolar lavage (BAL) fluid, secretion of Th2-type cytokines, particularly IL-10, was more predominant than Th1-type cytokines, and expression of regulated on activation normal T cell expressed and secreted (RANTES), p53, transforming growth factor (TGF)-β, and inducible nitric oxide synthase (iNOS) increased in a time-dependent manner. Fibrotic histopathological changes peaked on day 7 and decreased 14 days after exposure. Expression of cyclooxygenase-2 (COX-2), mesothelin, and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) also peaked on day 7, while that of TGF-β peaked on days 7 and 14. Secretion of histamine in BAL fluid decreased in a time-dependent manner. Consequently, we suggest that the brain is the target organ of semi-SWCNTs brought into the lung, and conductance as well as length may be critical factors affecting the intensity and duration of the inflammatory response following SWCNT exposure.
碳纳米管(CNTs)的毒理学研究已迫切需要,因为 CNTs 的新兴多种应用正在出现。在制造过程中获得的 CNTs 的物理化学性质,如形状、直径、电导率、表面电荷和表面化学性质,在毒性中起着关键作用。在这项研究中,我们分离了单壁碳纳米管(SWCNTs)的半导体成分(半-SWCNTs),并评估了气管内滴注后 1、7、14 和 28 天的毒性,以确定电导率的作用。暴露于半-SWCNTs 显著增加了小鼠的生长,并显著降低了脑重与体重的相对比值。单核细胞向血液中的募集呈时间依赖性增加,并且在暴露后 28 天观察到显著的血液学变化。在支气管肺泡灌洗液(BAL)中,Th2 型细胞因子,特别是 IL-10 的分泌比 Th1 型细胞因子更为明显,并且调节激活正常 T 细胞表达和分泌(RANTES)、p53、转化生长因子(TGF)-β和诱导型一氧化氮合酶(iNOS)的表达呈时间依赖性增加。纤维化组织病理学变化在第 7 天达到峰值,并在暴露后 14 天减少。环氧合酶-2(COX-2)、间皮素和磷酸化信号转导和转录激活因子 3(pSTAT3)的表达也在第 7 天达到峰值,而 TGF-β的表达在第 7 天和第 14 天达到峰值。BAL 液中组胺的分泌呈时间依赖性减少。因此,我们认为大脑是进入肺部的半-SWCNTs 的靶器官,电导率以及长度可能是影响 SWCNT 暴露后炎症反应强度和持续时间的关键因素。