POLARIS Research Center, Department of Environmental Science, University of Milano Bicocca, 1, piazza della Scienza, I-20126 Milan, Italy.
Toxicol Lett. 2012 Mar 7;209(2):136-45. doi: 10.1016/j.toxlet.2011.11.015. Epub 2011 Dec 9.
Particulate matter (PM) has been associated to adverse health effects in exposed population and DNA damage has been extensively reported in in vitro systems exposed to fine PM (PM2.5). The ability to induce gene expression profile modulation, production of reactive oxygen species (ROS) and strand breaks to DNA molecules has been investigated in A549 cells exposed to winter and summer Milan PM2.5.
A549 cells, exposed to 10 μg/cm(2) of both winter and summer PM2.5, showed increased cytotoxicity at 24h and a significant increase of ROS at 3h of treatment. Despite these similar effects winter PM induced a higher number of gene modulation in comparison with summer PM. Both PMs modulated genes related to the response to xenobiotic stimuli (CYP1A1, CYP1B1, TIPARP, ALDH1A3, AHRR) and to the cell-cell signalling (GREM1) pathways with winter PM2.5 inducing higher fold increases. Moreover the winter fraction modulated also JUN (cell-cell signalling), GDF15, SIPA1L2 (signal transduction), and HMOX1 (oxidative stress). Two genes, epiregulin (EREG) and FOS-like antigen1 (FOSL1), were significantly up-regulated by summer PM2.5. The results obtained with the microarray approach have been confirmed by qPCR and by the analysis of CYP1B1 expression. Comet assay evidenced that winter PM2.5 induced more DNA strand breaks than the summer one.
Winter PM2.5 is able to induce gene expression alteration, ROS production and DNA damage. These effects are likely to be related to the CYP enzyme activation in response to the polycyclic aromatic hydrocarbons (PAHs) adsorbed on particle surface.
颗粒物（PM）已被证明与暴露人群的不良健康影响有关，并且在体外系统中广泛报道了细颗粒物（PM2.5）暴露会导致 DNA 损伤。已经研究了 A549 细胞暴露于冬季和夏季米兰 PM2.5 时诱导基因表达谱调节、活性氧（ROS）产生和 DNA 分子链断裂的能力。
A549 细胞暴露于 10μg/cm2 的冬季和夏季 PM2.5，在 24 小时时显示出更高的细胞毒性，并且在处理 3 小时时 ROS 显著增加。尽管这些影响相似，但冬季 PM 诱导的基因调节数量高于夏季 PM。两种 PM 都调节了与异生物质刺激反应（CYP1A1、CYP1B1、TIPARP、ALDH1A3、AHRR）和细胞间信号转导（GREM1）途径相关的基因，冬季 PM2.5 诱导的倍数增加更高。此外，冬季分数还调节了 JUN（细胞间信号转导）、GDF15、SIPA1L2（信号转导）和 HMOX1（氧化应激）。两个基因，表皮调节素（EREG）和 FOS 样抗原 1（FOSL1），被夏季 PM2.5 显著上调。微阵列方法获得的结果通过 qPCR 和 CYP1B1 表达分析得到了证实。彗星试验证明冬季 PM2.5 诱导的 DNA 链断裂比夏季 PM2.5 多。
冬季 PM2.5 能够诱导基因表达改变、ROS 产生和 DNA 损伤。这些效应可能与多环芳烃（PAHs）吸附在颗粒表面上激活 CYP 酶有关。
