Analysis of gene expression changes in A549 cells induced by organic compounds from respirable air particles

作者：Libalova Helena; Krckova Simona; Uhlirova Katerina; Klema Jiri; Ciganek Miroslav; Roessner Pavel Jr; Sram Radim J; Vondracek Jan; Machala Miroslav; Topinka Jan^*

来源：Mutation Research-Fundamental and Molecular Mechanisms of Mutagenesis, 2014, 770: 94-105.

DOI：10.1016/j.mrfmmm.2014.10.002

• Ah receptor
• A549 cells
• Gene expression profile
• PAHs
• PM2.5

A number of toxic effects of respirable ambient air particles (genotoxic effects, inflammation, oxidative damage) have been attributed to organic compounds bound onto the particle surface. In this study, we analyzed global gene expression changes caused by the extractable organic matters (E0M5) from respirable airborne particles %26lt;2.5 pin (PM2.5), collected at 3 localities from heavily polluted areas of the Czech Republic and a control locality with low pollution levels, in human lung epithelial A549 cells. %26lt;br%26gt;Although the sampled localities differed in both extent and sources of air pollution, E0M5 did not induce substantially different gene expression profiles. The number of transcripts deregulated in A549 cells treated with the lowest EOM concentration (10 vg/m1) ranged from 65 to 85 in 4 sampling localities compared to the number of transcripts deregulated after 30 vg/m1 and 60 vg/m1 of E0M5, which ranged from 90 to 109, and from 149 to 452, respectively. We found numerous commonly deregulated genes and pathways related to activation of the aryl hydrocarbon receptor (AhR) and metabolism of xenobiotics and endogenous compounds. We further identified deregulation of expression of the genes involved in pro-inflammatory processes, oxidative stress response and in cancer and developmental pathways, such as TGF-p and Wnt signaling pathways. No cell cycle arrest, DNA repair or pro-apoptotic responses were identified at the transcriptional level after the treatment of A549 cells with E0M5. %26lt;br%26gt;In conclusion, numerous processes and pathways deregulated in response to E0M5 suggest a significant role of activated AhR. Interestingly, we did not observe substantial gene expression changes related to DNA damage response, possibly due to the antagonistic effect of non-genotoxic EOM components. Moreover, a comparison of EOM effects with other available data on modulation of global gene expression suggests possible overlap among the effects of PM2.5, E0M5 and various types of AhR agonists.

• 出版日期2014-12