a Department of Medicine , Duke University Medical Center , Durham , North Carolina , USA.
J Toxicol Environ Health B Crit Rev. 2013;16(6):381-94. doi: 10.1080/10937404.2013.832649.
Exposure to particulate matter (PM) is consistently associated with increased morbidity and mortality rate. The mechanisms for these adverse health effects have been vigorously investigated for many years, but remain uncertain, in part due to the complex interactions between host and exposure. Over the past decade, the use of global gene expression profiling has increased to investigate molecular changes in an attempt to gain more insight into the complex mechanisms that underlie the adverse health effects induced by PM. These experiments have been performed mostly in cell cultures, in part due to the easy availability and maneuverability of different cell types. Whether or not the results obtained from these in vitro experiments are relevant to human exposure is unclear. In this study, cell culture studies were reviewed that used microarray technology to measure global gene expression in response to PM and the findings discussed in the context of global gene expression results obtained from animal and human exposure studies. Ten in vitro studies were identified from PubMed that reported global gene expression results in response to PM exposure. Despite difference in cell types, microarray platforms, incubation time, and PM sources and doses, these experiments showed commonality in the expression of genes and pathways, especially xenobiotic metabolism, oxidative stress, and inflammation. These gene expression profiles were consistent with results from animal and human controlled exposure experiments. The in vitro experiments also uncovered novel biological mechanisms that may be important in PM-induced health effects reported in epidemiological studies. Data indicate that in vitro microarray experiments complement animal and human exposure studies and allow the PM-associated health research to focus on the "toxic" components in PM and novel mechanisms, and may enhance risk assessment beyond the current mass-based standards.
暴露于颗粒物（PM）与发病率和死亡率的增加密切相关。多年来，人们一直在大力研究这些不良健康影响的机制，但仍不确定，部分原因是宿主与暴露之间的复杂相互作用。在过去的十年中，人们越来越多地使用全基因表达谱分析来研究分子变化，试图更深入地了解 PM 引起的不良健康影响背后的复杂机制。这些实验主要在细胞培养物中进行，部分原因是不同细胞类型的易得性和可操作性。这些体外实验的结果是否与人类暴露有关尚不清楚。在本研究中，综述了使用微阵列技术测量 PM 暴露后全基因表达的细胞培养研究，并根据动物和人类暴露研究中获得的全基因表达结果讨论了这些发现。从 PubMed 中确定了 10 项体外研究，这些研究报告了 PM 暴露后全基因表达的结果。尽管细胞类型、微阵列平台、孵育时间以及 PM 来源和剂量存在差异，但这些实验在基因和途径的表达上表现出共性，特别是外来生物代谢、氧化应激和炎症。这些基因表达谱与动物和人类对照暴露实验的结果一致。体外实验还揭示了可能在流行病学研究中报道的 PM 诱导健康影响中起重要作用的新的生物学机制。数据表明，体外微阵列实验补充了动物和人类暴露研究，使 PM 相关健康研究能够专注于 PM 中的“毒性”成分和新机制，并可能超越当前基于质量的标准，增强风险评估。
