Institut National de Recherche et de Sécurité (INRS), Vandoeuvre-lès-Nancy Cedex, France.
Systems Biology Ireland, School of Medicine and Medical Sciences, University College Dublin, Belfield, Ireland.
Nanotoxicology. 2021 Mar;15(2):238-256. doi: 10.1080/17435390.2020.1851418. Epub 2020 Dec 17.
Inhalation of multi-walled carbon nanotubes (MWCNTs) induces lung inflammation. Depending on industrial applications, CNTs with different physicochemical characteristics are produced and workers can potentially be exposed. This raises concerns about the long-term health effects of these nanomaterials. Because of the wide variety of MWCNTs, it is essential to study the toxicological effects of CNTs of various shapes and to better understand the impact physical and chemical properties have on their toxicity. In this study, rats were exposed by nose-only to two pristine MWCNTs with different morphologies: the long and thick NM-401 or the short and thin NM-403. After four weeks of inhalation, animals were euthanized at four different times during the recovery period: three days (short-term), 30 and 90 days (intermediate-term) and 180 days (long-term). Analyses of the transcriptome in the whole lung and the proteome in the bronchoalveolar lavage fluid of exposed animals were performed to understand the MWCNT underlying mechanisms of toxicity. Following inhalation of NM-401, we observed a dose-dependent increase in the number of differentially expressed genes and proteins, whereas there is no clear difference between the two concentrations of NM-403. After NM-403 inhalation, the number of differentially expressed genes and proteins varied less between the four post-exposure times compared to NM-401, which supports the postulation of a persistent effect of this type of CNT. Our toxicogenomics approaches give insights into the different toxicological profile following MWCNT exposure.
吸入多壁碳纳米管(MWCNTs)会引起肺部炎症。根据不同的工业应用,会生产出具有不同物理化学特性的 CNT,而工人则有可能接触到这些 CNT。这引发了人们对这些纳米材料长期健康影响的担忧。由于 MWCNTs 的种类繁多,研究各种形状的 CNT 的毒理学效应以及更好地了解物理和化学性质对其毒性的影响至关重要。在这项研究中,通过鼻腔吸入方式使大鼠仅暴露于两种具有不同形态的原始 MWCNTs 中:长而粗的 NM-401 或短而细的 NM-403。吸入四周后,在恢复期间的四个不同时间点对动物进行安乐死:三天(短期)、30 天和 90 天(中期)以及 180 天(长期)。对暴露动物的整个肺部的转录组和支气管肺泡灌洗液的蛋白质组进行分析,以了解 MWCNT 的毒性作用机制。在吸入 NM-401 后,我们观察到差异表达基因和蛋白质的数量呈剂量依赖性增加,而 NM-403 的两种浓度之间没有明显差异。与 NM-401 相比,吸入 NM-403 后,四个暴露后时间之间差异表达基因和蛋白质的数量变化较小,这支持了这种 CNT 具有持续作用的假说。我们的毒理基因组学方法深入了解了 MWCNT 暴露后的不同毒理学特征。