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

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.

Keywords::

• biological pathway
• biological network
• differential gene regulation
• differential protein regulation
• high aspect ratio nanomaterial

Acknowledgement

The authors thank Dr Srikanth S. Nadadur at the National Institute of Environmental Health Sciences (NIEHS) who conceived the ideas for this study and provided critical guidance, insight and support. They thank Dr Somenath Mitra at New Jersey Institute of Technology for providing the MWCNT and Dr Nianqiang Wu at West Virginia University for providing the TiO₂-NB, as part of the NIEHS Nanotechnology Environmental Health and Safety consortium effort. Part of this research was performed using EMSL, a national scientific user facility sponsored by the Department of Energy's Office of Biological and Environmental Research and located at Pacific Northwest National Laboratory. This work was supported by the National Institute of Environmental Health Sciences [RC2ES018025-01S1 to F.A.W.], [RC2ES018742-01S1 to A.H.] and [1RC2ES018786-01S1 to G.O.].