Vinca Institute of Nuclear Sciences, PO Box 522, Belgrade, Serbia.
Nanotechnology. 2010 Jan 8;21(1):015102. doi: 10.1088/0957-4484/21/1/015102. Epub 2009 Nov 30.
Carbon nanotubes are unique one-dimensional macromolecules with promising applications in biology and medicine. Since their toxicity is still under debate, here we present a study investigating the genotoxic properties of purified single wall carbon nanotubes (SWCNTs), multiwall carbon nanotubes (MWCNTs), and amide functionalized purified SWCNTs on cultured human lymphocytes employing cytokinesis block micronucleus assay and enumeration of gamma H2AX foci as a measure of double strand breaks (DSBs) of the DNA in normal human fibroblasts. SWCNTs induce micronuclei (MN) formation in lymphocytes and decrease the proliferation potential (CBPI) of cells. In a fibroblast cell line the same dose of SWCNTs induces gamma H2AX foci 2.7-fold higher than in a control. Amide functionalized purified SWCNTs behave differently: they do not disturb the cell proliferation potential of harvested lymphocytes, but induce micronuclei to a higher extent than SWCNTs. When applied on fibroblasts, amide functionalized SWCNTs also induce gamma H2AX foci, 3.18-fold higher than the control. The cellular effects of MWCNTs display the broad spectrum of clastogenic properties seen as the highest incidence of induced lymphocyte micronuclei and anaphase bridges among nuclei in binucleated cells. Surprisingly, the incidence of induced gamma H2AX foci was not as high as was expected by the micronucleus test, which indicates that MWCNTs act as clastogen and aneugen agents simultaneously. Biological endpoints investigated in this study indicate a close relationship between the electrochemical properties of carbon nanotubes and observed genotoxicity.
碳纳米管是独特的一维大分子,在生物学和医学中有广泛的应用前景。由于其毒性仍存在争议,我们在此研究了纯化的单壁碳纳米管(SWCNTs)、多壁碳纳米管(MWCNTs)和酰胺功能化的纯化 SWCNTs 在培养的人淋巴细胞中的遗传毒性特性,采用细胞有丝分裂阻断微核试验和γH2AX 焦点的计数来衡量正常人类成纤维细胞中的 DNA 双链断裂(DSBs)。SWCNTs 诱导淋巴细胞中的微核(MN)形成,并降低细胞的增殖潜力(CBPI)。在成纤维细胞系中,相同剂量的 SWCNTs 诱导的 γH2AX 焦点比对照高 2.7 倍。酰胺功能化的纯化 SWCNTs 的行为不同:它们不会干扰收获的淋巴细胞的细胞增殖潜力,但诱导微核的程度高于 SWCNTs。当应用于成纤维细胞时,酰胺功能化的 SWCNTs 也会诱导 γH2AX 焦点,比对照高 3.18 倍。MWCNTs 的细胞效应显示出广泛的断裂剂特性,表现为诱导淋巴细胞微核和双核细胞中核间后期桥的发生率最高。令人惊讶的是,诱导 γH2AX 焦点的发生率并不像微核试验所预期的那样高,这表明 MWCNTs 同时作为断裂剂和着丝粒剂发挥作用。本研究中研究的生物学终点表明,碳纳米管的电化学性质与观察到的遗传毒性之间存在密切关系。