Structural Defects Play a Major Role in the Acute Lung Toxicity of Multiwall Carbon Nanotubes: Toxicological Aspects
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- 作者：Julie Muller ; Franç ; ois Huaux ; Antonio Fonseca ; Janos B. Nagy ; Nicolas Moreau ; Monique Delos ; Encarnacion Raymundo-Piñ ; ero ; Franç ; ois Bé ; guin ; Micheline Kirsch-Volders ; Ivana Fenog
- 刊名：Chemical Research in Toxicology
- 出版年：2008
- 出版时间：September 15, 2008
- 年：2008
- 卷：21
- 期：9
- 页码：1698-1705
- 全文大小：443K
- 年卷期：v.21,no.9(September 15, 2008)
- ISSN：1520-5010
文摘
Experimental studies indicate that carbon nanotubes (CNTs) have the potential to induce adverse pulmonary effects, including alveolitis, fibrosis, and genotoxicity in epithelial cells. Here, we explored the physicochemical determinants of these toxic responses with progressively and selectively modified CNTs: ground multiwall CNTs modified by heating at 600 °C (loss of oxygenated carbon functionalities and reduction of oxidized metals) or at 2400 °C (annealing of structural defects and elimination of metals) and by grinding the material that had been heated at 2400 °C before (introduction of structural defects in a metal-deprived framework). The CNTs were administered intratracheally (2 mg/rat) to Wistar rats to evaluate the short-term response (3 days) in bronchoalveolar lavage fluid (LDH, proteins, cellular infiltration, IL-1β, and TNF-α). The long-term (60 days) lung response was assessed biochemically by measuring the lung hydroxyproline content and histologically. In vitro experiments were also performed on rat lung epithelial cells to assess the genotoxic potential of the modified CNTs with the cytokinesis block micronucleus assay. The results show that the acute pulmonary toxicity and the genotoxicity of CNT were reduced upon heating but restored upon grinding, indicating that the intrinsic toxicity of CNT is mainly mediated by the presence of defective sites in their carbon framework.