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

Toxicology. 2015 Feb 3;328:66-74. doi: 10.1016/j.tox.2014.12.012. Epub 2014 Dec 13.

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: Coculture; Correlation; Gene expression; In vitro; In vivo.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cells, Cultured
  • Coculture Techniques
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Epithelial Cells / drug effects*
  • Epithelial Cells / metabolism
  • Gene Expression Profiling / methods
  • Gene Expression Regulation / drug effects
  • Gene Regulatory Networks / drug effects
  • Genetic Markers
  • Humans
  • Inhalation Exposure / adverse effects
  • Lung / blood supply*
  • Lung / drug effects*
  • Lung / metabolism
  • Male
  • Mice, Inbred C57BL
  • Nanotubes, Carbon / toxicity*
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / metabolism
  • Reproducibility of Results
  • Risk Assessment

Substances

  • Genetic Markers
  • Nanotubes, Carbon
  • RNA, Messenger