Comparative lung toxicity of engineered nanomaterials utilizing in vitro, ex vivo and in vivo approaches.
Comparative lung toxicity of engineered nanomaterials utilizing in vitro, ex vivo and in vivo approaches.
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DOI：
10.1186/s12951-014-0047-3
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发表时间：
2014-11-26
影响因子：
10.2
通讯作者：
Gilmour MI
中科院分区：
文献类型：
--
作者：
Kim YH;Boykin E;Stevens T;Lavrich K;Gilmour MI
尽管目前对工程纳米材料的管制是在一种新化学品的背景下进行的，或作为现有化学品的一种新用途，但危险评估在很大程度上仍然依赖于母体化合物的历史毒性研究资料，可能没有考虑到与工程纳米材料的小尺寸和高表面积有关的特殊性质。虽然适当筛选和预测ENM的潜在毒性很重要，但也有人担心，目前的毒性测试将需要更多的实验动物，应该开发和验证可靠的替代品。在这里，我们评估了比较呼吸毒性ENM在三种不同的方法，采用在体内，体外和离体毒性测试方法。本研究测试了五种ENM（SiO2（10）、CeO 2（23）、CeO 2（88）、TiO 2（10）和TiO 2（200）;括号表示平均ENM直径（nm））的毒性。通过口咽抽吸将CD-1小鼠以100 μg的剂量暴露于ENM。小鼠肺组织切片和肺泡巨噬细胞也分别暴露于浓度为22-132和3.1-100 μg/mL的ENM。在暴露后4和/或24小时评估肺损伤和炎症的生物标志物。小尺寸ENM（SiO2（10），CeO 2（23），但不是TiO 2（10））在小鼠体内（体内）显著引起促炎反应，表明在肺部观察到的毒性取决于尺寸和化学成分。同样，与其他ENM相比，SiO2（10）和/或CeO 2（23）在肺组织切片（离体）和肺泡巨噬细胞（体外）中的毒性也更大。类似的炎症反应模式（例如，当采用基于细胞表面积（μg/cm 2）而不是培养基体积（μg/mL）的剂量度量时，在离体和体外都观察到白细胞介素-6）。暴露于ENM诱导急性肺部炎症反应的大小和化学成分依赖性的方式。细胞培养和肺切片技术提供了相似的效应特征，有助于弥合我们对体内、离体和体外毒性结局的理解中的差距。本文的在线版本（doi：10.1186/s12951-014-0047-3）包含补充材料，可供授权用户使用。
Although engineered nanomaterials (ENM) are currently regulated either in the context of a new chemical, or as a new use of an existing chemical, hazard assessment is still to a large extent reliant on information from historical toxicity studies of the parent compound, and may not take into account special properties related to the small size and high surface area of ENM. While it is important to properly screen and predict the potential toxicity of ENM, there is also concern that current toxicity tests will require even heavier use of experimental animals, and reliable alternatives should be developed and validated. Here we assessed the comparative respiratory toxicity of ENM in three different methods which employed in vivo, in vitro and ex vivo toxicity testing approaches. Toxicity of five ENM (SiO2 (10), CeO2 (23), CeO2 (88), TiO2 (10), and TiO2 (200); parentheses indicate average ENM diameter in nm) were tested in this study. CD-1 mice were exposed to the ENM by oropharyngeal aspiration at a dose of 100 μg. Mouse lung tissue slices and alveolar macrophages were also exposed to the ENM at concentrations of 22–132 and 3.1-100 μg/mL, respectively. Biomarkers of lung injury and inflammation were assessed at 4 and/or 24 hr post-exposure. Small-sized ENM (SiO2 (10), CeO2 (23), but not TiO2 (10)) significantly elicited pro-inflammatory responses in mice (in vivo), suggesting that the observed toxicity in the lungs was dependent on size and chemical composition. Similarly, SiO2 (10) and/or CeO2 (23) were also more toxic in the lung tissue slices (ex vivo) and alveolar macrophages (in vitro) compared to other ENM. A similar pattern of inflammatory response (e.g., interleukin-6) was observed in both ex vivo and in vitro when a dose metric based on cell surface area (μg/cm2), but not culture medium volume (μg/mL) was employed. Exposure to ENM induced acute lung inflammatory effects in a size- and chemical composition-dependent manner. The cell culture and lung slice techniques provided similar profiles of effect and help bridge the gap in our understanding of in vivo, ex vivo, and in vitro toxicity outcomes. The online version of this article (doi:10.1186/s12951-014-0047-3) contains supplementary material, which is available to authorized users.
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影响因子：
10
作者：
Hinderliter PM;Minard KR;Orr G;Chrisler WB;Thrall BD;Pounds JG;Teeguarden JG
通讯作者：
Teeguarden JG
影响因子：
10.4
作者：
Bonner JC;Silva RM;Taylor AJ;Brown JM;Hilderbrand SC;Castranova V;Porter D;Elder A;Oberdörster G;Harkema JR;Bramble LA;Kavanagh TJ;Botta D;Nel A;Pinkerton KE
通讯作者：
Pinkerton KE
影响因子：
5
作者：
Ma, Jane Y.;Zhao, Hongwen;Ma, Joseph K.
通讯作者：
Ma, Joseph K.
DOI：
10.1164/rccm.201002-0185oc
发表时间：
2010-12-01
影响因子：
24.7
作者：
Kim, Yong Ho;Fazlollahi, Farnoosh;Crandall, Edward D.
通讯作者：
Crandall, Edward D.
影响因子：
4.6
作者：
Hiraiwa K;van Eeden SF
通讯作者：
van Eeden SF