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Multi-walled carbon nanotube-induced gene expression in vitro: concordance with in vivo studies.

Authors
Snyder-Talkington-BN; Dong-C; Zhao-X; Dymacek-J; Porter-DW; Wolfarth-MG; Castranova-V; Qian-Y; Guo-NL
Source
Toxicology 2015 Feb; 328:66-74
NIOSHTIC No.
20045468
Abstract
There is a current interest in reducing the in vivo toxicity testing of nanomaterials in animals by increasing toxicity testing using in vitro cellular assays; however, toxicological results are seldom concordant between in vivo and in vitro models. This study compared global multi-walled carbon nanotube (MWCNT)-induced gene expression from human lung epithelial and microvascular endothelial cells in monoculture and coculture with gene expression from mouse lungs exposed to MWCNT. Using a cutoff of 10% false discovery rate and 1.5 fold change, we determined that there were more concordant genes (gene expression both up- or downregulated in vivo and in vitro) expressed in both cell types in coculture than in monoculture. When reduced to only those genes involved in inflammation and fibrosis, known outcomes of in vivo MWCNT exposure, there were more disease-related concordant genes expressed in coculture than monoculture. Additionally, different cellular signaling pathways are activated in response to MWCNT dependent upon culturing conditions. As coculture gene expression better correlated with in vivo gene expression, we suggest that cellular cocultures may offer enhanced in vitro models for nanoparticle risk assessment and the reduction of in vivo toxicological testing.
Keywords
Nanotechnology; Laboratory-testing; In-vitro-studies; In-vivo-studies; Cellular-function; Cellular-reactions; Bioassays; Analytical-instruments; Analytical-models; Genes; Cell-culture-techniques; Cell-cultures; Lung-cells; Animals; Humans; Laboratory-animals; Author Keywords: Coculture; Gene expression; In vivo; In vitro; Correlation
Contact
Nancy L. Guo, Mary Babb Randolph Cancer Center and Department of Community Medicine, West Virginia University, Morgantown, WV 26506-9300, USA
CODEN
TXCYAC
Publication Date
20150203
Document Type
Journal Article
Email Address
lguo@hsc.wvu.edu
Fiscal Year
2015
NTIS Accession No.
NTIS Price
Identifying No.
M122014
ISSN
0300-483X
NIOSH Division
HELD
Priority Area
Manufacturing
Source Name
Toxicology
State
WV
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