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Transcriptomics analysis of lungs and peripheral blood of silica-exposed rats.

Authors
Sellamuthu-R; Umbright-C; Roberts-JR; Chapman-R; Young-S-H; Richardson-D; Cumpston-J; McKinney-W; Chen-BT; Frazer-D; Li-S; Kashon-M; Joseph-P
Source
Inhal Toxicol 2012 Aug; 24(9):570-579
NIOSHTIC No.
20041285
Abstract
Minimally invasive approaches to detect/predict target organ toxicity have significant practical applications in occupational toxicology. The potential application of peripheral blood transcriptomics as a practical approach to study the mechanisms of silica-induced pulmonary toxicity was investigated. Rats were exposed by inhalation to crystalline silica (15 mg/m3, 6 h/day, 5 days) and pulmonary toxicity and global gene expression profiles of lungs and peripheral blood were determined at 32 weeks following termination of exposure. A significant elevation in bronchoalveolar lavage fluid lactate dehydrogenase activity and moderate histological changes in the lungs, including type II pneumocyte hyperplasia and fibrosis, indicated pulmonary toxicity in the rats. Similarly, significant infiltration of neutrophils and elevated monocyte chemotactic protein-1 levels in the lungs showed pulmonary inflammation in the rats. Microarray analysis of global gene expression profiles identified significant differential expression [>1.5- fold change and false discovery rate (FDR) p < 0.01] of 520 and 537 genes, respectively, in the lungs and blood of the exposed rats. Bioinformatics analysis of the differentially expressed genes demonstrated significant similarity in the biological processes, molecular networks, and canonical pathways enriched by silica exposure in the lungs and blood of the rats. Several genes involved in functions relevant to silica-induced pulmonary toxicity such as inflammation, respiratory diseases, cancer, cellular movement, fibrosis, etc, were found significantly differentially expressed in the lungs and blood of the silica-exposed rats. The results of this study suggested the potential application of peripheral blood gene expression profiling as a toxicologically relevant and minimally invasive surrogate approach to study the mechanisms underlying silica-induced pulmonary toxicity.
Keywords
Laboratory-animals; Laboratory-techniques; Laboratory-testing; Exposure-assessment; Exposure-methods; Exposure-levels; Lung; Pulmonary-system; Immune-reaction; Dose-response; Particulates; Silica-dusts; Author Keywords: Crystalline silica; pulmonary toxicity; gene expression profile; blood; mechanisms
Contact
Pius Joseph, MS 3014, Toxicology and Molecular Biology Branch, National Institute for Occupational Safety and Health (NIOSH), 1095 Willowdale Road, Morgantown, WV 26505
CODEN
INHTE5
CAS No.
7631-86-9; 14808-60-7
Publication Date
20120801
Document Type
Journal Article
Email Address
pcj5@cdc.gov
Fiscal Year
2012
NTIS Accession No.
NTIS Price
Identifying No.
B08292012
Issue of Publication
9
ISSN
0895-8378
NIOSH Division
HELD
Priority Area
Construction; Manufacturing
Source Name
Inhalation Toxicology
State
WV
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