Abstract

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.

抽象的

吸入多壁碳纳米管（MWCNT）会引起肺部炎症。根据工业应用，会生产出具有不同理化特性的碳纳米管，并且可能会暴露工人。这引起了对这些纳米材料的长期健康影响的关注。由于MWCNT种类繁多，因此必须研究各种形状的CNT的毒理学作用，并更好地了解理化性质对其毒性的影响。在这项研究中，大鼠仅通过鼻子暴露于两种不同形态的原始MWCNT：长而厚的NM-401或短而薄的NM-403。吸入四周后，在恢复期的四个不同时间对动物实施安乐死：三天（短期），30天和90天（中期）和180天（长期）。对暴露动物的全肺转录组和支气管肺泡灌洗液中的蛋白质组进行了分析，以了解MWCNT潜在的毒性机制。吸入NM-401后，我们观察到差异表达的基因和蛋白质的数量呈剂量依赖性增加，而两种浓度的NM-403之间没有明显差异。吸入NM-403后，与NM-401相比，在四个暴露后时间之间差异表达的基因和蛋白质的数量变化较小，这支持了此类CNT的持久作用。我们的毒理基因组学方法可洞悉MWCNT暴露后的不同毒理学特征。