Multi-wall carbon nanotube (MWCNT)-induced gene expression in the mouse lung: implication of carcinogenesis risk.
Pacurari-M; Qian-Y; Hubbs-A; Porter-D; Wolfarth-M; Luo-D; Wan-Y; Castranova-V; Guo-N
Toxicologist 2011 Mar; 120(Suppl 2):253-254
MWCNT's fibrous-like shape and durability suggest they may pose a similar carcinogenic effect on humans as asbestos. Therefore, this study sought to investigate how previously identified lung cancer prognostic biomarkers and the related cancer signaling pathways are affected in the mouse lung following in vivo pharyngeal aspiration of MWCNT. A total of 63 identified lung cancer prognostic biomarker genes were analyzed using quantitative PCR assays in the mouse lung exposed by aspiration to 0, 10, 20, 40, 80 ug of MWCNT at 7-days and 56-days post-exposure. At 7- and 56-days post-exposures, a set of 7 genes and a set of 11 genes showed significant differential expression in the mouse lungs exposed to MWCNT vs. unexposed control groups, respectively. These significant genes could clearly separate the control group from the treated group over the time series in hierarchical gene clustering analysis. Furthermore, 4 genes from these two sets of significant genes, Ccdc99, Msx2, Nos2 and Wif1, showed significant mRNA expression perturbations at both time points. It was also found that the expression changes of these 4 overlapped genes at 7-days post-exposure were attenuated at 56-days post-exposure. The results of MWCNT exposure-induced gene expression changes reveal the characteristics of carcinogenesis and may indicate the association of MWCNT exposure with lung cancer progression. These results also indicate that MWCNT exposure may induce the alteration of several key carcinogenesis-related signaling transduction pathways. Taken together, the results obtained from this study indicate the potential lung carcinogenetic effects of MWCNT exposure in humans and could potentially be used for the medical surveillance for MWCNT workers.
Biological-effects; Cancer; Carcinogenesis; Carcinogenicity; Exposure-assessment; Genes; Genetic-factors; Genetics; Inhalation-studies; Laboratory-animals; Laboratory-testing; Lung-cancer; Lung-cells; Lung-disease; Lung-disorders; Lung-fibrosis; Lung-irritants; Medical-research; Nanotechnology; Physical-properties; Physiological-effects; Pulmonary-function; Pulmonary-system; Pulmonary-system-disorders; Quantitative-analysis; Respiratory-hypersensitivity; Respiratory-irritants; Respiratory-system-disorders; Risk-analysis; Risk-factors; Statistical-analysis
The Toxicologist. Society of Toxicology 50th Annual Meeting and ToxExpo, March 6-10, 2011, Washington, DC