Three human cell types respond to multi-walled carbon nanotubes and titanium dioxide nanobelts with cell-specific transcriptomic and proteomic expression patterns

Susan C. Tilton, Norman J. Karin, Ana Tolic, Yumei Xie, Xianyin Lai, Raymond F. Hamilton, Katrina M. Waters, Andrij Holian, Frank Witzmann, Galya Orr

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

The growing use of engineered nanoparticles (NPs) in commercial and medical applications raises the urgent need for tools that can predict NP toxicity. Global transcriptome and proteome analyses were conducted on three human cell types, exposed to two high aspect ratio NP types, to identify patterns of expression that might indicate high versus low NP toxicity. Three cell types representing the most common routes of human exposure to NPs, including macrophage-like (THP-1), small airway epithelial and intestinal (Caco-2/HT29-MTX) cells, were exposed to TiO2 nanobelts (TiO2-NB; high toxicity) and multi-walled carbon nanotubes (MWCNT; low toxicity) at low (10 μg/mL) and high (100 μg/mL) concentrations for 1 and 24 h. Unique patterns of gene and protein expressions were identified for each cell type, with no differentially expressed (p < 0.05, 1.5-fold change) genes or proteins overlapping across all three cell types. While unique to each cell type, the early response was primarily independent of NP type, showing similar expression patterns in response to both TiO2-NB and MWCNT. The early response might, therefore, indicate a general response to insult. In contrast, the 24 h response was unique to each NP type. The most significantly (p < 0.05) enriched biological processes in THP-1 cells indicated TiO2-NB regulation of pathways associated with inflammation, apoptosis, cell cycle arrest, DNA replication stress and genomic instability, while MWCNT-regulated pathways indicated increased cell proliferation, DNA repair and anti-apoptosis. These two distinct sets of biological pathways might, therefore, underlie cellular responses to high and low NP toxicity, respectively.

Original languageEnglish
Pages (from-to)533-548
Number of pages16
JournalNanotoxicology
Volume8
Issue number5
DOIs
StatePublished - Aug 2014

Fingerprint

Nanobelts
Carbon Nanotubes
Carbon Dioxide
Proteomics
Nanoparticles
Titanium dioxide
Carbon nanotubes
Cells
Toxicity
Cell death
Proteins
DNA
Genes
Apoptosis
Biological Phenomena
HT29 Cells
titanium dioxide
Macrophages
Genomic Instability
Cell proliferation

Keywords

  • Biological network
  • Biological pathway
  • Differential gene regulation
  • Differential protein regulation
  • High aspect ratio nanomaterial

ASJC Scopus subject areas

  • Biomedical Engineering
  • Toxicology

Cite this

Three human cell types respond to multi-walled carbon nanotubes and titanium dioxide nanobelts with cell-specific transcriptomic and proteomic expression patterns. / Tilton, Susan C.; Karin, Norman J.; Tolic, Ana; Xie, Yumei; Lai, Xianyin; Hamilton, Raymond F.; Waters, Katrina M.; Holian, Andrij; Witzmann, Frank; Orr, Galya.

In: Nanotoxicology, Vol. 8, No. 5, 08.2014, p. 533-548.

Research output: Contribution to journalArticle

Tilton, Susan C. ; Karin, Norman J. ; Tolic, Ana ; Xie, Yumei ; Lai, Xianyin ; Hamilton, Raymond F. ; Waters, Katrina M. ; Holian, Andrij ; Witzmann, Frank ; Orr, Galya. / Three human cell types respond to multi-walled carbon nanotubes and titanium dioxide nanobelts with cell-specific transcriptomic and proteomic expression patterns. In: Nanotoxicology. 2014 ; Vol. 8, No. 5. pp. 533-548.
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AB - The growing use of engineered nanoparticles (NPs) in commercial and medical applications raises the urgent need for tools that can predict NP toxicity. Global transcriptome and proteome analyses were conducted on three human cell types, exposed to two high aspect ratio NP types, to identify patterns of expression that might indicate high versus low NP toxicity. Three cell types representing the most common routes of human exposure to NPs, including macrophage-like (THP-1), small airway epithelial and intestinal (Caco-2/HT29-MTX) cells, were exposed to TiO2 nanobelts (TiO2-NB; high toxicity) and multi-walled carbon nanotubes (MWCNT; low toxicity) at low (10 μg/mL) and high (100 μg/mL) concentrations for 1 and 24 h. Unique patterns of gene and protein expressions were identified for each cell type, with no differentially expressed (p < 0.05, 1.5-fold change) genes or proteins overlapping across all three cell types. While unique to each cell type, the early response was primarily independent of NP type, showing similar expression patterns in response to both TiO2-NB and MWCNT. The early response might, therefore, indicate a general response to insult. In contrast, the 24 h response was unique to each NP type. The most significantly (p < 0.05) enriched biological processes in THP-1 cells indicated TiO2-NB regulation of pathways associated with inflammation, apoptosis, cell cycle arrest, DNA replication stress and genomic instability, while MWCNT-regulated pathways indicated increased cell proliferation, DNA repair and anti-apoptosis. These two distinct sets of biological pathways might, therefore, underlie cellular responses to high and low NP toxicity, respectively.

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