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Peripheral blood gene expression profiling reveals silica-induced pulmonary toxicity.
Sellamuthu-R; Umbright-C; Roberts-J; Chapman-R; Young-S; Richardson-D; Leonard-D; McKinney-W; Chen-B; Frazer-D; Li-S; Kashon-M; Joseph-P
Toxicologist 2011 Mar; 120(Suppl 2):498
The present research aimed to investigate peripheral blood gene expression profiling as a minimally invasive surrogate approach to study silica-induced pulmonary toxicity. Rats were exposed to crystalline silica by inhalation (15 mg/m3, 6 hours/day, 5 days). Pulmonary damage and blood gene expression profiles were determined at various latency periods (0 - 16 weeks). Silica exposure resulted in pulmonary toxicity in the rats as evidenced by histological changes in the lungs and elevation of LDH activity in the bronchoalveolar lavage fluid (BALF). Analysis of global gene expression profiles in the blood of the rats identified genes that were differentially expressed in response to silica exposure. The differential blood gene expression profiles correlated with the pulmonary toxicity parameters in the silica exposed rats. Genes involved in biological functions such as inflammatory response, cancer, pulmonary damage, oxidative stress, energy metabolism, fibrosis, etc, were found differentially expressed in the blood of the silica exposed rats compared with the controls. Induction of pulmonary inflammation in the silica exposed rats, as suggested by differential expression of inflammatory response genes in the blood, was supported by significant increases in the number of neutrophils and macrophages as well as the activity of pro-inflammatory chemokines - MCP1 and MIP2, observed in the BALF of the silica exposed rats. A silica-responsive blood gene expression signature developed using the gene expression data predicted with significant accuracy the exposure of rats to lower concentrations (1 and 2 mg/m3) of silica. Taken together our findings suggest the potential application of peripheral blood gene expression profiling as an efficient surrogate approach to study silica-induced pulmonary toxicity. Disclaimer: The findings and conclusions in this abstract have not been formally disseminated by NIOSH and should not be constructed to represent any agency determination or policy.
Biological-effects; Cell-biology; Cytology; Laboratory-animals; Laboratory-testing; Lung-cells; Lung-disorders; Molecular-biology; Pulmonary-disorders; Pulmonary-system; Pulmonary-system-disorders; Quantitative-analysis; Respiratory-infections; Respiratory-system-disorders; Statistical-analysis; Toxic-effects; Toxicology; Animals; Animal-studies; Respiratory-system-disorders
The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC