 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Jun 20, 2017 |
| Title |
Molecular mechanisms of pulmonary response progression in crystalline silica exposed rats |
| Organism |
Rattus norvegicus |
| Experiment type |
Expression profiling by array
|
| Summary |
The capability to detect target organ toxicity as well as to determine the molecular mechanisms underlying such toxicity by employing surrogate biospecimens that can be obtained by a non-invasive or minimally invasive procedure has significant advantage in occupational toxicology. Pulmonary toxicity and global gene expression profile in the lungs, peripheral blood and bronchoalveolar lavage (BAL) cells were determined in rats at 44-weeks following pulmonary exposure to crystalline silica (15 mg/m3, 6-hours/day, 5 days). A significant elevation in lactate dehydrogenase activity and albumin content observed in the BAL fluid suggested the induction of pulmonary toxicity in the silica exposed rats. Similarly, the observation of histological alterations, mainly type II pneumocyte hyperplasia and fibrosis, in the lungs further confirmed silica-induced pulmonary toxicity in the rats. A significant increase in the number of neutrophils and elevated monocyte chemotactic protein 1 level in the BAL fluids suggested silica-induced pulmonary inflammation in the rats. Determination of global gene expression profile in the lungs, BAL cells, and peripheral blood of the silica exposed rats identified 144, 236, and 51 significantly differentially expressed genes (SDEGs), respectively, compared with the corresponding control samples. Bioinformatics analysis of the SDEGs demonstrated a remarkable similarity in the biological functions, molecular networks and canonical pathways that were significantly affected by silica exposure in the lungs, BAL cells and blood of the rats. Induction of inflammation was identified, based on the bioinformatics analysis of the significantly differentially expressed genes in the lungs, blood and BAL cells, as the major molecular mechanism underlying the silica-induced pulmonary toxicity. The findings of our study demonstrated the potential application of global gene expression profiling of peripheral blood and BAL cells as a valuable minimally invasive approach to study silica-induced pulmonary toxicity in rats.
|
| |
|
| Overall design |
Pulmonary toxicity and global gene expression profile in the lungs, peripheral blood and bronchoalveolar lavage (BAL) cells were determined in rats at 44-weeks following pulmonary exposure to crystalline silica.
LUNG: 12 samples were analyzed in this experiment. The RNA from rat lung samples was isolated for gene expression studies. Rats (6) were exposed to crystalline silica by inhalation (15 mg/m3, 6 hours/day, 5 days) and air (6). Lung gene expression profiling was performed using RNA isolated from rat lung samples, 6 for silica exposed and 6 for air exposed controls at 44 weeks post-exposure time period.
BLOOD: 12 samples were analyzed in this experiment. The RNA from rat blood samples was isolated for gene expression studies. Rats (6) were exposed to crystalline silica by inhalation (15 mg/m3, 6 hours/day, 5 days) and air (6). Blood gene expression profiling was performed using rat blood samples, 6 for silica exposed and 6 for air exposed controls at 44 weeks post-exposure time period.
BALF: 12 samples were analyzed in this experiment. The RNA from rat brancheoalveolar lavage fluid (BALF) cells was isolated for gene expression studies. Rats (6) were exposed to crystalline silica by inhalation (15 mg/m3, 6 hours/day, 5 days) and air (6). Gene expression profiling of BALF cells was performed using rat BALF cells samples, 6 for silica exposed and 6 for air exposed controls at 44 weeks post-exposure time period.
|
| |
|
| Contributor(s) |
Sellamuthu R, Umbright C, Roberts JR, Young S, Richardson D, McKinney W, Chen B, Frazer D, Li S, Kashon M, Joseph P |
| Citation(s) |
28317464 |
| |
| Submission date |
Oct 15, 2012 |
| Last update date |
Jun 20, 2017 |
| Contact name |
Rajendran Sellamuthu |
| E-mail(s) |
rajsella@indiana.edu
|
| Organization name |
National Institute for Occupational Safety and Health
|
| Department |
HELD
|
| Lab |
Molecular Carcinogenesis
|
| Street address |
1095 Willowdale Rd
|
| City |
Morgantown |
| State/province |
WV |
| ZIP/Postal code |
26505 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL6101 |
Illumina ratRef-12 v1.0 expression beadchip |
|
| Samples (36)
|
| GSM1019550 |
Lung_0mg silica_44 week post-exposure_rep5 |
| GSM1019551 |
Lung_15mg silica_44 week post-exposure_rep6 |
| GSM1019552 |
Lung_15mg silica_44 week post-exposure_rep4 |
| GSM1019553 |
Lung_0mg silica_44 week post-exposure_rep2 |
| GSM1019554 |
Lung_15mg silica_44 week post-exposure_rep3 |
| GSM1019555 |
Lung_0mg silica_44 week post-exposure_rep4 |
| GSM1019556 |
Lung_15mg silica_44 week post-exposure_rep1 |
| GSM1019557 |
Lung_0mg silica_44 week post-exposure_rep3 |
| GSM1019558 |
Lung_0mg silica_44 week post-exposure_rep6 |
| GSM1019559 |
Lung_15mg silica_44 week post-exposure_rep2 |
| GSM1019560 |
Lung_0mg silica_44 week post-exposure_rep1 |
| GSM1019561 |
Lung_15mg silica_44 week post-exposure_rep5 |
| GSM1019562 |
Blood_15mg silica_44 week post-exposure_rep2 |
| GSM1019563 |
Blood_15mg silica_44 week post-exposure_rep5 |
| GSM1019564 |
Blood_15mg silica_44 week post-exposure_rep3 |
| GSM1019565 |
Blood_15mg silica_44 week post-exposure_rep1 |
| GSM1019566 |
Blood_0mg silica_44 week post-exposure_rep2 |
| GSM1019567 |
Blood_0mg silica_44 week post-exposure_rep4 |
| GSM1019568 |
Blood_0mg silica_44 week post-exposure_rep5 |
| GSM1019569 |
Blood_15mg silica_44 week post-exposure_rep4 |
| GSM1019570 |
Blood_0mg silica_44 week post-exposure_rep1 |
| GSM1019571 |
Blood_0mg silica_44 week post-exposure_rep3 |
| GSM1019572 |
Blood_0mg silica_44 week post-exposure_rep6 |
| GSM1019573 |
Blood_15mg silica_44 week post-exposure_rep6 |
| GSM1019574 |
BALF Cells_15mg silica_44 week post-exposure_rep4 |
| GSM1019575 |
BALF Cells_0mg silica_44 week post-exposure_rep2 |
| GSM1019576 |
BALF Cells_15mg silica_44 week post-exposure_rep2 |
| GSM1019577 |
BALF Cells_15mg silica_44 week post-exposure_rep5 |
| GSM1019578 |
BALF Cells_0mg silica_44 week post-exposure_rep4 |
| GSM1019579 |
BALF Cells_15mg silica_44 week post-exposure_rep1 |
| GSM1019580 |
BALF Cells_0mg silica_44 week post-exposure_rep6 |
| GSM1019581 |
BALF Cells_0mg silica_44 week post-exposure_rep3 |
| GSM1019582 |
BALF Cells_15mg silica_44 week post-exposure_rep6 |
| GSM1019583 |
BALF Cells_0mg silica_44 week post-exposure_rep1 |
| GSM1019584 |
BALF Cells_0mg silica_44 week post-exposure_rep5 |
| GSM1019585 |
BALF Cells_15mg silica_44 week post-exposure_rep3 |
|
| Relations |
| BioProject |
PRJNA177561 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE41572_BALF_non-normalized_data.txt.gz |
4.0 Mb |
(ftp)(http) |
TXT |
| GSE41572_BLOOD_non-normalized_data.txt.gz |
4.0 Mb |
(ftp)(http) |
TXT |
| GSE41572_LUNG_non-normalized_data.txt.gz |
3.9 Mb |
(ftp)(http) |
TXT |
| GSE41572_RAW.tar |
2.8 Mb |
(http)(custom) |
TAR |
| Processed data included within Sample table |
|
|
|
|
 |
Less...
More...