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一种毒理学套件,适用于比较模型人肺细胞对柴油尾气颗粒及其提取物的平行毒性反应。

A toxicology suite adapted for comparing parallel toxicity responses of model human lung cells to diesel exhaust particles and their extracts.

作者信息

Turner Jane, Hernandez Mark, Snawder John E, Handorean Alina, McCabe Kevin M

机构信息

Department of Civil, Environmental and Architectural Engineering, University of Colorado, Boulder, Colorado, USA.

Biomonitoring Research, National Institute for Occupational Safety and Health, Cincinnati, Ohio, USA.

出版信息

Aerosol Sci Technol. 2015;49(8):599-610. doi: 10.1080/02786826.2015.1053559.

Abstract

Epidemiological studies have shown that exposure to airborne particulate matter can be an important risk factor for some common respiratory diseases. While many studies have shown that particulate matter exposures are associated with inflammatory reactions, the role of specific cellular responses in the manifestation of primary hypersensitivities, and the progression of respiratory diseases remains unclear. In order to better understand mechanisms by which particulate matter can exert adverse health effects, more robust approaches to support studies are warranted. In response to this need, a group of accepted toxicology assays were adapted to create an analytical suite for screening and evaluating the effects of important, ubiquitous atmospheric pollutants on two model human lung cell lines (epithelial and immature macrophage). To demonstrate the utility of this suite, responses to intact diesel exhaust particles, and mass-based equivalent doses of their organic extracts were examined. Results suggest that extracts have the potential to induce greater biological responses than those associated with their colloidal counterpart. Additionally, macrophage cells appear to be more susceptible to the cytotoxic effects of both intact diesel exhaust particles and their organic extract, than epithelial cells tested in parallel. As designed, the suite provided a more robust basis for characterizing toxicity mechanisms than the analysis of any individual assay. Findings suggest that cellular responses to particulate matter are cell line dependent, and show that the collection and preparation of PM and/or their extracts have the potential to impact cellular responses relevant to screening fundamental elements of respiratory toxicity.

摘要

流行病学研究表明,接触空气中的颗粒物可能是一些常见呼吸道疾病的重要风险因素。虽然许多研究表明,接触颗粒物与炎症反应有关,但特定细胞反应在原发性超敏反应表现以及呼吸道疾病进展中的作用仍不清楚。为了更好地理解颗粒物对健康产生不利影响的机制,需要更有力的方法来支持相关研究。为满足这一需求,对一组公认的毒理学检测方法进行了调整,以创建一套分析方法,用于筛选和评估重要的、普遍存在的大气污染物对两种人类肺模型细胞系(上皮细胞和未成熟巨噬细胞)的影响。为了证明这套方法的实用性,研究人员检测了对完整柴油废气颗粒及其基于质量的等效剂量有机提取物的反应。结果表明,提取物可能比与其胶体对应物相关的物质诱导更大的生物学反应。此外,与同时检测的上皮细胞相比,巨噬细胞似乎对完整柴油废气颗粒及其有机提取物的细胞毒性作用更敏感。按照设计,这套方法为表征毒性机制提供了比任何单个检测分析更有力的基础。研究结果表明,细胞对颗粒物的反应取决于细胞系,并且表明颗粒物及其提取物的收集和制备有可能影响与筛选呼吸道毒性基本要素相关的细胞反应。

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