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Multiwalled carbon nanotube-induced gene signatures in the mouse lung: potential predictive value for human lung cancer risk and prognosis.

Authors
Guo-NL; Wan-Y-W; Denvir-J; Porter-DW; Pacurari-M; Wolfarth-MG; Castranova-V; Qian-Y
Source
J Toxicol Environ Health, A 2012 Sep; 75(18):1129-1153
NIOSHTIC No.
20041501
Abstract
Concerns over the potential for multiwalled carbon nanotubes (MWCNT) to induce lung carcinogenesis have emerged. This study sought to (1) identify gene expression signatures in the mouse lungs following pharyngeal aspiration of well-dispersed MWCNT and (2) determine if these genes were associated with human lung cancer risk and progression. Genome-wide mRNA expression profiles were analyzed in mouse lungs (n = 160) exposed to 0, 10, 20, 40, or 80 microg of MWCNT by pharyngeal aspiration at 1, 7, 28, and 56 d postexposure. By using pairwise statistical analysis of microarray (SAM) and linear modeling, 24 genes were selected, which have significant changes in at least two time points, have a more than 1.5-fold change at all doses, and are significant in the linear model for the dose or the interaction of time and dose. Additionally, a 38-gene set was identified as related to cancer from 330 genes differentially expressed at d 56 postexposure in functional pathway analysis. Using the expression profiles of the cancer-related gene set in 8 mice at d 56 postexposure to 10 microg of MWCNT, a nearest centroid classification accurately predicts human lung cancer survival with a significant hazard ratio in training set (n = 256) and test set (n = 186). Furthermore, both gene signatures were associated with human lung cancer risk (n = 164) with significant odds ratios. These results may lead to development of a surveillance approach for early detection of lung cancer and prognosis associated with MWCNT in the workplace.
Keywords
Nanotechnology; Lung-cancer; Cancer; Carcinogenesis; Toxic-effects; Laboratory-animals; Laboratory-testing; Humans; Risk-analysis; Genes; Genotoxic-effects; Lung; Lung-cells; Respiratory-system-disorders; Pulmonary-system-disorders; Recombinant-DNA; Exposure-assessment; Exposure-levels; Mathematical-models; Statistical-analysis; Analytical-models; Dose-response
Contact
Yong Qian, Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA
CODEN
JTEHD6
CAS No.
7440-44-0
Publication Date
20120901
Document Type
Journal Article
Email Address
yaq2@cdc.gov
Fiscal Year
2012
NTIS Accession No.
NTIS Price
Identifying No.
B09262012
Issue of Publication
18
ISSN
1528-7394
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
Journal of Toxicology and Environmental Health, Part A: Current Issues
State
WV
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