Duncan Kelly E, Cook Philip M, Gavett Stephen H, Dailey Lisa A, Mahoney Ron K, Ghio Andrew J, Roggli Victor L, Devlin Robert B
Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U,S, Environmental Protection Agency, Research Triangle Park, NC 27711, USA.
Part Fibre Toxicol. 2014 Jan 8;11:2. doi: 10.1186/1743-8977-11-2.
An abnormally high incidence of lung disease has been observed in the residents of Libby, Montana, which has been attributed to occupational and environmental exposure to fibrous amphiboles originating from a nearby contaminated vermiculite mine. The composition of Libby amphibole (LA) is complex and minimal toxicity data are available. In this study, we conduct a comparative particle toxicity analysis of LA compared with standard reference asbestiform amphibole samples.
Primary human airway epithelial cells (HAEC) were exposed to two different LA samples as well as standard amphibole reference samples. Analysis of the samples included a complete particle size distribution analysis, calculation of surface area by electron microscopy and by gas adsorption and quantification of surface-conjugated iron and hydroxyl radical production by the fibers. Interleukin-8 mRNA levels were quantified by qRT-PCR to measure relative pro-inflammatory response induced in HAEC in response to amphibole fiber exposure. The relative contribution of key physicochemical determinants on the observed pro-inflammatory response were also evaluated.
The RTI amosite reference sample contained the longest fibers and demonstrated the greatest potency at increasing IL-8 transcript levels when evaluated on an equal mass basis. The two LA samples and the UICC amosite reference sample consisted of similar particle numbers per milligram as well as similar particle size distributions and induced comparable levels of IL-8 mRNA. A strong correlation was observed between the elongated particle (aspect ratio ≥3:1) dose metrics of length and external surface area. Expression of the IL-8 data with respect to either of these metrics eliminated the differential response between the RTI amosite sample and the other samples that was observed when HAEC were exposed on an equal mass basis.
On an equal mass basis, LA is as potent as the UICC amosite reference sample at inducing a pro-inflammatory response in HAEC but is less potent than the RTI amosite sample. The results of this study show that the particle length and particle surface area are highly correlated metrics that contribute significantly to the toxicological potential of these amphibole samples with respect to the inflammogenic response induced in airway epithelial cells.
在蒙大拿州利比的居民中观察到肺部疾病的异常高发病率，这归因于职业和环境暴露于源自附近受污染蛭石矿的纤维状闪石。利比闪石（LA）的成分复杂，且可用的毒性数据极少。在本研究中，我们对LA与标准参考石棉状闪石样品进行了比较颗粒毒性分析。
将原代人气道上皮细胞（HAEC）暴露于两种不同的LA样品以及标准闪石参考样品。对样品的分析包括完整的粒度分布分析、通过电子显微镜和气体吸附计算表面积以及定量纤维表面结合的铁和羟基自由基的产生。通过qRT-PCR定量白细胞介素-8 mRNA水平，以测量HAEC在暴露于闪石纤维后诱导的相对促炎反应。还评估了关键物理化学决定因素对观察到的促炎反应的相对贡献。
当以等质量为基础进行评估时，RTI铁石棉参考样品包含最长的纤维，并且在增加IL-8转录水平方面表现出最大的效力。两个LA样品和UICC铁石棉参考样品每毫克的颗粒数相似，粒度分布也相似，并诱导了相当水平的IL-8 mRNA。在细长颗粒（长径比≥3:1）的长度和外表面积剂量指标之间观察到强相关性。相对于这些指标中的任何一个表达IL-8数据，消除了在以等质量为基础暴露HAEC时观察到的RTI铁石棉样品与其他样品之间的差异反应。
在等质量基础上，LA在诱导HAEC促炎反应方面与UICC铁石棉参考样品一样有效，但比RTI铁石棉样品效力低。本研究结果表明，颗粒长度和颗粒表面积是高度相关的指标，对这些闪石样品在气道上皮细胞中诱导的炎症反应的毒理学潜力有显著贡献。
