Molecular Toxicology Research Laboratory, NIH-RCMI-Center for Environmental Health, Jackson State University, 1400 Lynch Street, Box 18540, Jackson, Mississippi 39217, USA.
Environ Toxicol. 2010 Dec;25(6):608-21. doi: 10.1002/tox.20621.
The development of nanotechnologies may lead to environmental release of nanomaterials that are potentially harmful to human health. Among the nanomaterials, multiwalled carbon nanotubes (MWCNTs) are already commercialized in various products which can be in direct contact with populations. However, few studies address their potential toxicity. Although a few reports on the cytotoxicity of carbon nanotubes (CNTs) have been published, very little is known about their toxicity or genotoxicity in mammalian cells. We have for the first time compared the clastogenic/genotoxic potential of functionalized and nonfunctionalized MWCNTs in bone marrow cells of Swiss-Webster mice; using mitotic index (MI), chromosome aberrations (CA), micronuclei (MN) formation, and DNA damage in leukocytes as toxicologic endpoints. Six groups of five male mice, each weighing ∼30 ± 2 g, were administered intraperitoneally, once a day for five days with doses of 0.25, 0.5, 0.75, mg/kg body weight (BW) of functionalized and nonfunctionalized MWCNTs. Four vehicle control groups (negative) and a positive control group (carbon black) were also made of 5 mice each. Chromosome and micronuclei from bone marrow cells and comet slides from leukocytes were examined following standard protocols. The results demonstrated that MWCNTs exposure significantly increased (P < 0.05) the number of structural chromosomal aberrations, the frequency of micronucleated cells and the level of DNA damage, and decreased the mitotic index in treated groups compared to control groups. MWCNTs were shown to be toxic at sufficiently high concentrations, however purified functionalized MWCNTs had a higher clastogenic/genotoxic potential compared to nonfunctionalized form of MWCNT. The results of our study suggest that exposure to MWCNT has the potential to cause genetic damage. Hence, careful monitoring should be done with respect to designing/synthesizing biocompatible carbon nanomaterials. Further characterization of their systemic toxicity, genotoxicity and carcinogenicity is also essential.
纳米技术的发展可能导致纳米材料释放到环境中，这些材料可能对人类健康造成潜在危害。在这些纳米材料中，多壁碳纳米管（MWCNTs）已经商业化应用于各种可直接与人群接触的产品中。然而，很少有研究涉及它们的潜在毒性。虽然已经发表了一些关于碳纳米管（CNTs）细胞毒性的报告，但对于它们在哺乳动物细胞中的毒性或遗传毒性知之甚少。我们首次比较了功能化和非功能化 MWCNTs 在瑞士-韦伯斯特小鼠骨髓细胞中的致裂/遗传毒性潜力；使用有丝分裂指数（MI）、染色体畸变（CA）、微核（MN）形成和白细胞中的 DNA 损伤作为毒理学终点。六组每组 5 只雄性小鼠，体重约 30±2g，每天腹腔注射一次，连续 5 天，剂量为 0.25、0.5、0.75mg/kg 体重（BW）的功能化和非功能化 MWCNTs。还设置了 4 个阴性载体对照组（阴性对照）和 1 个阳性对照组（炭黑），每组 5 只。根据标准方案检查骨髓细胞的染色体和微核以及白细胞的彗星载玻片。结果表明，与对照组相比，MWCNTs 暴露显著增加了（P<0.05）结构染色体畸变的数量、微核细胞的频率和 DNA 损伤的水平，并且降低了有丝分裂指数。MWCNTs 在足够高的浓度下显示出毒性，但与非功能化 MWCNT 相比，纯化的功能化 MWCNTs 具有更高的致裂/遗传毒性潜力。我们的研究结果表明，暴露于 MWCNT 有可能导致遗传损伤。因此，在设计/合成生物相容性碳纳米材料时应进行仔细监测。进一步表征其系统毒性、遗传毒性和致癌性也是必要的。
