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Adaptive changes in global gene expression profile of lung carcinoma A549 cells acutely exposed to distinct types of AhR ligands.
- Source :
-
Toxicology letters [Toxicol Lett] 2018 Aug; Vol. 292, pp. 162-174. Date of Electronic Publication: 2018 Apr 25. - Publication Year :
- 2018
-
Abstract
- Exposure to persistent ligands of aryl hydrocarbon receptor (AhR) has been found to cause lung cancer in experimental animals, and lung adenocarcinomas are often associated with enhanced AhR expression and aberrant AhR activation. In order to better understand the action of toxic AhR ligands in lung epithelial cells, we performed global gene expression profiling and analyze TCDD-induced changes in A549 transcriptome, both sensitive and non-sensitive to CH223191 co-treatment. Comparison of our data with results from previously reported microarray and ChIP-seq experiments enabled us to identify candidate genes, which expression status reflects exposure of lung cancer cells to TCDD, and to predict processes, pathways (e.g. ER stress, Wnt/β-cat, IFNɣ, EGFR/Erbb1), putative TFs (e.g. STAT, AP1, E2F1, TCF4), which may be implicated in adaptive response of lung cells to TCDD-induced AhR activation. Importantly, TCDD-like expression fingerprint of selected genes was observed also in A549 cells exposed acutely to both toxic (benzo[a]pyrene, benzo[k]fluoranthene) and endogenous AhR ligands (2-(1H-Indol-3-ylcarbonyl)-4-thiazolecarboxylic acid methyl ester and 6-formylindolo[3,2-b]carbazole). Overall, our results suggest novel cellular candidates, which could help to improve monitoring of AhR-dependent transcriptional activity during acute exposure of lung cells to distinct types of environmental pollutants.<br /> (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Subjects :
- A549 Cells
Azo Compounds toxicity
Basic Helix-Loop-Helix Transcription Factors metabolism
Benzo(a)pyrene toxicity
Carbazoles toxicity
Fluorenes toxicity
Gene Expression Profiling methods
Gene Regulatory Networks drug effects
Humans
Indoles toxicity
Ligands
Lung Neoplasms metabolism
Oligonucleotide Array Sequence Analysis
Polychlorinated Dibenzodioxins toxicity
Pyrazoles toxicity
Receptors, Aryl Hydrocarbon metabolism
Signal Transduction drug effects
Thiazoles toxicity
Time Factors
Transcription, Genetic drug effects
Transcriptional Activation drug effects
Basic Helix-Loop-Helix Transcription Factors agonists
Environmental Pollutants toxicity
Gene Expression Regulation, Neoplastic drug effects
Lung Neoplasms genetics
Receptors, Aryl Hydrocarbon agonists
Transcriptome drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1879-3169
- Volume :
- 292
- Database :
- MEDLINE
- Journal :
- Toxicology letters
- Publication Type :
- Academic Journal
- Accession number :
- 29704546
- Full Text :
- https://doi.org/10.1016/j.toxlet.2018.04.024