Mrakovcic Maria, Meindl Claudia, Leitinger Gerd, Roblegg Eva, Fröhlich Eleonore
*Center for Medical Research, Medical University of Graz; Institute for Cell Biology, Histology and Embryology, Medical University of Graz; and Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, Karl-Franzens-University of Graz, 8010 Graz, Austria.
*Center for Medical Research, Medical University of Graz; Institute for Cell Biology, Histology and Embryology, Medical University of Graz; and Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, Karl-Franzens-University of Graz, 8010 Graz, Austria *Center for Medical Research, Medical University of Graz; Institute for Cell Biology, Histology and Embryology, Medical University of Graz; and Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, Karl-Franzens-University of Graz, 8010 Graz, Austria.
Toxicol Sci. 2015 Mar;144(1):114-27. doi: 10.1093/toxsci/kfu260. Epub 2014 Dec 10.
Long carbon nanotubes (CNTs) resemble asbestos fibers due to their high length to diameter ratio and they thus have genotoxic effects. Another parameter that might explain their genotoxic effects is contamination with heavy metal ions. On the other hand, short (1-2 µm) CNTs do not resemble asbestos fibers, and, once purified from contaminations, they might be suitable for medical applications. To identify the role of fiber thickness and surface properties on genotoxicity, well-characterized short pristine and carboxylated single-walled (SCNTs) and multi-walled (MCNTs) CNTs of different diameters were studied for cytotoxicity, the cell's response to oxidative stress (immunoreactivity against hemoxygenase 1 and glutathione levels), and in a hypoxanthine guanine phosphoribosyltransferase (HPRT) assay using V79 chinese hamster fibroblasts and human lung adenocarcinoma A549 cells. DNA repair was demonstrated by measuring immunoreactivity against activated histone H2AX protein. The number of micronuclei as well as the number of multinucleated cells was determined. CNTs acted more cytotoxic in V79 than in A549 cells. Plain and carboxylated thin (<8 nm) SCNTs and MCNTs showed greater cytotoxic potential and carboxylated CNTs showed indication for generating oxidative stress. Multi-walled CNTs did not cause HPRT mutation, micronucleus formation, DNA damage, interference with cell division, and oxidative stress. Carboxylated, but not plain, SCNTs showed indication for in vitro DNA damage according to increase of H2AX-immunoreactive cells and HPRT mutation. Although short CNTs presented a low in vitro genotoxicity, functionalization of short SCNTs can render these particles genotoxic.
长碳纳米管（CNT）由于其高长径比而类似于石棉纤维，因此具有遗传毒性作用。另一个可能解释其遗传毒性作用的参数是重金属离子污染。另一方面，短（1 - 2微米）的CNT不像石棉纤维，并且一旦从污染物中纯化出来，它们可能适用于医学应用。为了确定纤维厚度和表面性质对遗传毒性的作用，研究了具有良好特征的不同直径的短原始和羧基化单壁（SCNT）和多壁（MCNT）CNT对细胞毒性、细胞对氧化应激的反应（针对血红素加氧酶1的免疫反应性和谷胱甘肽水平），并使用V79中国仓鼠成纤维细胞和人肺腺癌A549细胞进行次黄嘌呤鸟嘌呤磷酸核糖转移酶（HPRT）测定。通过测量针对活化组蛋白H2AX蛋白的免疫反应性来证明DNA修复。确定了微核的数量以及多核细胞的数量。CNT在V79细胞中比在A549细胞中表现出更强的细胞毒性。普通和羧基化的薄（<8纳米）SCNT和MCNT显示出更大的细胞毒性潜力，并且羧基化的CNT显示出产生氧化应激的迹象。多壁CNT不会引起HPRT突变、微核形成、DNA损伤、干扰细胞分裂和氧化应激。根据H2AX免疫反应性细胞的增加和HPRT突变，羧基化而非普通的SCNT显示出体外DNA损伤的迹象。尽管短CNT在体外表现出低遗传毒性，但短SCNT的功能化可使这些颗粒具有遗传毒性。
