Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

System-based identification of toxicity pathways associated with multi-walled carbon nanotube-induced pathological responses.

Authors
Snyder-Talkington-BN; Dymacek-J; Porter-DW; Wolfarth-MG; Mercer-RR; Pacurari-M; Denvir-J; Castranova-V; Qian-Y; Guo-NL
Source
Toxicol Appl Pharmacol 2013 Oct; 272(2):476-489
NIOSHTIC No.
20043048
Abstract
The fibrous shape and biopersistence of multi-walled carbon nanotubes (MWCNT) have raised concern over their potential toxicity after pulmonary exposure. As in vivo exposure to MWCNT produced a transient inflammatory and progressive fibrotic response, this study sought to identify significant biological processes associated with lung inflammation and fibrosis pathology data, based upon whole genome mRNA expression, bronchoaveolar lavage scores, and morphometric analysis from C57BL/6J mice exposed by pharyngeal aspiration to 0, 10, 20, 40, or 80g MWCNT at 1, 7, 28, or 56days post-exposure. Using a novel computational model employing non-negative matrix factorization and Monte Carlo Markov Chain simulation, significant biological processes with expression similar to MWCNT-induced lung inflammation and fibrosis pathology data in mice were identified. A subset of genes in these processes was determined to be functionally related to either fibrosis or inflammation by Ingenuity Pathway Analysis and was used to determine potential significant signaling cascades. Two genes determined to be functionally related to inflammation and fibrosis, vascular endothelial growth factor A (vegfa) and C-C motif chemokine 2 (ccl2), were confirmed by in vitro studies of mRNA and protein expression in small airway epithelial cells exposed to MWCNT as concordant with in vivo expression. This study identified that the novel computational model was sufficient to determine biological processes strongly associated with the pathology of lung inflammation and fibrosis and could identify potential toxicity signaling pathways and mechanisms of MWCNT exposure which could be used for future animal studies to support human risk assessment and intervention efforts.
Keywords
Nanotechnology; Biological-effects; Exposure-levels; Fibrous-bodies; Lung; Lung-fibrosis; Pathology; Animals; Laboratory-animals; Genes; Fibrosis; Author Keywords: Multi-walled carbon nanotubes; Signaling pathways; Computational toxicology; In vivo studies
Contact
Yong 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
20131015
Document Type
Journal Article
Email Address
yaq2@cdc.gov
Fiscal Year
2014
NTIS Accession No.
NTIS Price
Identifying No.
M082013
Issue of Publication
2
ISSN
0041-008X
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
Toxicology and Applied Pharmacology
State
WV
TOP