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Multi-walled carbon nanotube-induced gene expression in the mouse lung: association with lung pathology.

Authors
Pacurari-M; Qian-Y; Porter-DW; Wolfarth-M; Wan-Y; Luo-D; Ding-M; Castranova-V; Guo-NL
Source
Toxicol Appl Pharmacol 2011 Aug; 255(1):18-31
NIOSHTIC No.
20039217
Abstract
Due to the fibrous shape and durability of multi-walled carbon nanotubes (MWCNT), concerns regarding their potential for producing environmental and human health risks, including carcinogenesis, have been raised. 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 pharyngeal aspiration of well-dispersed MWCNT. A total of 63 identified lung cancer prognostic biomarker genes and major signaling biomarker genes were analyzed in mouse lungs (n=80) exposed to 0, 10, 20, 40, or 80g of MWCNT by pharyngeal aspiration at 7 and 56days post-exposure using quantitative PCR assays. At 7 and 56days post-exposure, a set of 7 genes and a set of 11 genes, respectively, showed differential expression in the lungs of mice exposed to MWCNT vs. the control group. Additionally, these significant genes could separate the control group from the treated group over the time series in a hierarchical gene clustering analysis. Furthermore, 4 genes from these two sets of significant genes, coiled-coil domain containing-99 (Ccdc99), muscle segment homeobox gene-2 (Msx2), nitric oxide synthase-2 (Nos2), and wingless-type inhibitory factor-1 (Wif1), showed significant mRNA expression perturbations at both time points. It was also found that the expression changes of these 4 overlapping genes at 7days post-exposure were attenuated at 56days post-exposure. Ingenuity Pathway Analysis (IPA) found that several carcinogenic-related signaling pathways and carcinogenesis itself were associated with both the 7 and 11 gene signatures. Taken together, this study identifies that MWCNT exposure affects a subset of lung cancer biomarkers in mouse lungs.
Keywords
Nanotechnology; Environmental-health; Risk-factors; Carcinogens; Lung; Lung-cancer; Lung-cells; Lung-disease; Biomarkers; Humans; Genetic-factors; Genes; Author Keywords: Nanoparticles; Lung cancer; Biomarker; Gene expression; Molecular network analysis
Contact
Y. Qian, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, 1095 Willowdale Road, Morgantown, WV 26505-2888
CODEN
TXAPA9
Publication Date
20110815
Document Type
Journal Article
Email Address
yaq2@cdc.gov
Fiscal Year
2011
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
0041-008X
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
Toxicology and Applied Pharmacology
State
WV
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