E-GEOD-2565 - Transcription profiling of lung from mouse exposed to carbonyl chloride (phosgene) for different lengths of time to investigate the molecular mechanism of phosgene-induced lung injury

Status
Released on 25 June 2007, last updated on 3 May 2014
Organism
Mus musculus
Samples (97)
Array (1)
Protocols (3)
Description
Carbonyl chloride (phosgene) is a toxic industrial compound (TIC) widely used in industry for the production of synthetic products, such as polyfoam rubber, plastics, and dyes. Exposure to phosgene results in a latent (1-24 hr), potentially life-threatening pulmonary edema and irreversible acute lung injury. A genomic approach was utilized to investigate the molecular mechanism of phosgene-induced lung injury. CD-1 male mice were exposed whole-body to either air or a concentration x time (c x t) amount of 32 mg/m3 (8 ppm) phosgene for 20 min (640 mg x min/m3). Lung tissue was collected from air- or phosgene-exposed mice at 0.5, 1, 4, 8, 12, 24, 48, and 72 hr post-exposure. RNA was extracted from the lung and used as starting material for the probing of oligonucleotide microarrays to determine changes in gene expression following phosgene exposure. The data were analyzed using principal component analysis (PCA) to determine the greatest sources of data variability. A three-way analysis of variance (ANOVA) based on exposure, time, and sample was performed to identify the genes most significantly changed as a result of phosgene exposure. These genes were rank ordered by p-values and categorized based on molecular function and biological process. Some of the most significant changes in gene expression reflect changes in glutathione synthesis and redox regulation of the cell, including upregulation of glutathione S-transferase alpha-2, glutathione peroxidase 2, and glutamate-cysteine ligase, catalytic subunit (also known as γ-glutamyl cysteine synthetase). This is in agreement with previous observations describing changes in redox enzyme activity after phosgene exposure. We are also investigating other pathways that are responsive to phosgene exposure to identify mechanisms of toxicity and potential therapeutic targets.,Male CD-1 mice were exposed to air or 32 mg per cubic meter phosgene for 20 min and tissue collected at 30 min, 1 hr, 4 hr, 8 hr, 12 hr, 24 hr, 48 hr, or 72 hr before collection and analysis of lung tissue using oligonucleotide microarrays.,Keyword=phosgene,Keyword=mouse,Keyword=lung,Keyword=carbonyl chloride
Experiment types
transcription profiling by array, cell type comparison, co-expression, compound treatment
Contact
Citation
Genomic analysis of murine pulmonary tissue following carbonyl chloride inhalation. Sciuto AM, Phillips CS, Orzolek LD, Hege AI, Moran TS, Dillman JF 3rd.
MIAME
PlatformsProtocolsFactorsProcessedRaw
Files
Investigation descriptionE-GEOD-2565.idf.txt
Sample and data relationshipE-GEOD-2565.sdrf.txt
Raw data (3)E-GEOD-2565.raw.1.zip, E-GEOD-2565.raw.2.zip, E-GEOD-2565.raw.3.zip
Processed data (1)E-GEOD-2565.processed.1.zip
Array designA-AFFY-23.adf.txt
R ExpressionSetE-GEOD-2565.eSet.r
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