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Mechanisms of crystalline silica-induced pulmonary toxicity revealed by global gene expression profiling.

Authors
Sellamuthu-R; Umbright-C; Li-S; Kashon-M; Joseph-P
Source
Inhal Toxicol 2011 Dec; 23(14):927-937
NIOSHTIC No.
20040051
Abstract
A proper understanding of the mechanisms underlying crystalline silica-induced pulmonary toxicity has implications in the management and potential prevention of the adverse health effects associated with silica exposure including silicosis, cancer and several auto-immune diseases. Human lung type II epithelial cells and rat lungs exposed to crystalline silica were employed as experimental models to determine global gene expression changes in order to understand the molecular mechanisms underlying silica-induced pulmonary toxicity. The differential gene expression profile induced by silica correlated with its toxicity in the A549 cells. The biological processes perturbed by silica exposure in the A549 cells and rat lungs, as identified by the bioinformatics analysis of the differentially expressed genes, demonstrated significant similarity. Functional categorization of the differentially expressed genes identified cancer, cellular movement, cellular growth and proliferation, cell death, inflammatory response, cell cycle, cellular development, and genetic disorder as top ranking biological functions perturbed by silica exposure in A549 cells and rat lungs. Results of our study, in addition to confirming several previously identified molecular targets and mechanisms involved in silica toxicity, identified novel molecular targets and mechanisms potentially involved in silica-induced pulmonary toxicity. Further investigations, including those focused on the novel molecular targets and mechanisms identified in the current study may result in better management and, possibly, reduction and/or prevention of the potential adverse health effects associated with crystalline silica exposure.
Keywords
Toxicology; Toxic-materials; Toxic-effects; Respiratory-system-disorders; Pulmonary-system-disorders; Pulmonary-disorders; Lung-disease; Lung-disorders; Lung-function; Silica-dusts; Silicosis; Cancer; Autoimmunity; Inhalation-studies; Laboratory-animals; Laboratory-testing; Exposure-methods; Molecular-structure; Gene-mutation; Genotoxic-effects; Cell-function; Cellular-reactions; Cellular-structures; Cell-growth; Cell-migration; Biological-effects; Author Keywords: Crystalline silica; pulmonary toxicity; gene expression profile; 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, USA
CODEN
INHTE5
CAS No.
7631-86-9; 14808-60-7
Publication Date
20111201
Document Type
Journal Article
Email Address
pcj5@cdc.gov
Fiscal Year
2012
NTIS Accession No.
NTIS Price
Identifying No.
B12212011
Issue of Publication
14
ISSN
0895-8378
NIOSH Division
HELD
Priority Area
Construction; Manufacturing
Source Name
Inhalation Toxicology
State
WV
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