Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, UI Research Park, Iowa City, IA 52242-5000, USA.
Department of Occupational and Environmental Health, University of Iowa, UI Research Park, Iowa City, IA 52242-5000, USA.
Toxicology. 2014 Mar 20;317:31-9. doi: 10.1016/j.tox.2014.01.005. Epub 2014 Jan 19.
Human exposure to polybrominated diphenyl ethers (PBDEs) can occur via ingestion of indoor dust, inhalation of PBDE-contaminated air and dust-bound PBDEs. However, few studies have examined the pulmonary toxicity of particle-bound PBDEs, mainly due to the lack of an appropriate particle-cell exposure system. In this study we developed an in vitro exposure system capable of generating particle-bound PBDEs mimicking dusts containing PBDE congeners (BDEs 35, 47 and 99) and delivering them directly onto lung cells grown at an air-liquid interface (ALI). The silica particles and particles-coated with PBDEs ranged in diameter from 4.3 to 4.5 μm and were delivered to cells with no apparent aggregation. This experimental set up demonstrated high reproducibility and sensitivity for dosing control and distribution of particles. ALI exposure of cells to PBDE-bound particles significantly decreased cell viability and induced reactive oxygen species generation in A549 and NCI-H358 cells. In male Sprague-Dawley rats exposed via intratracheal insufflation (0.6 mg/rat), particle-bound PBDE exposures induced inflammatory responses with increased recruitment of neutrophils to the lungs compared to sham-exposed rats. The present study clearly indicates the potential of our exposure system for studying the toxicity of particle-bound compounds.
人类接触多溴二苯醚(PBDEs)可能通过摄入室内灰尘、吸入受 PBDE 污染的空气和灰尘结合的 PBDE 来实现。然而,很少有研究探讨颗粒结合的 PBDE 的肺毒性,主要是因为缺乏合适的颗粒细胞暴露系统。在这项研究中,我们开发了一种体外暴露系统,能够产生模拟含有 PBDE 同系物(BDEs 35、47 和 99)的灰尘的颗粒结合的 PBDE,并将其直接递送到在气液界面(ALI)上生长的肺细胞。直径为 4.3 至 4.5μm 的二氧化硅颗粒和涂覆有 PBDE 的颗粒被递送到细胞中,没有明显的聚集。这种实验装置表现出了高度的重现性和剂量控制以及颗粒分布的敏感性。A549 和 NCI-H358 细胞的 ALI 暴露于 PBDE 结合颗粒会显著降低细胞活力,并诱导活性氧的产生。在通过气管内滴注(0.6mg/rat)暴露于雄性 Sprague-Dawley 大鼠的情况下,与假暴露大鼠相比,颗粒结合的 PBDE 暴露会引起肺部中性粒细胞的募集增加,从而引发炎症反应。本研究清楚地表明,我们的暴露系统有潜力用于研究颗粒结合化合物的毒性。