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

Details

• Personal Author:
  Castranova, Vincent ; Dong C ; Dymacek J ; Guo NL ; Porter DW ; Qian Y ; Snyder-Talkington BN ; Wolfarth MG ; Zhao X
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Animals Biological Assay Cells, Cultured Genetics Laboratories Lung Occupational Health Respiratory System Safety
• Keywords:
  Analytical-instruments Analytical-models Author Keywords: Coculture Bioassays Cell-culture-techniques Cell-cultures Cellular-function Cellular-reactions Correlation Gene Expression Genes Humans In-vitro-studies In-vivo-studies In Vitro In Vivo Laboratory-animals Laboratory-testing Lung-cells Nanotechnology

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• ISSN:
  0300-483X
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  66-74
• Volume:
  328
• NIOSHTIC Number:
  nn:20045468
• Citation:
  Toxicology 2015 Feb; 328:66-74
• Contact Point Address:
  Nancy L. Guo, Mary Babb Randolph Cancer Center and Department of Community Medicine, West Virginia University, Morgantown, WV 26506-9300, USA
• Email:
  lguo@hsc.wvu.edu
• Federal Fiscal Year:
  2015
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Toxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:dd77da5def77e45481e6ac76cb8ba3e122d7dd121bf336560ecef02e3b936067bad0e1c666cf9899f5ba23ab041a081b2d08e5cb0e232c1438d17010ecaa34e5
• Download URL:
  https://stacks.cdc.gov/view/cdc/200878/cdc_200878_DS1.pdf
• File Type:
  [PDF - 813.18 KB ]