2007 NSTI Nanotechnology Conference and Trade Show - Nanotech 2007 - 10th Annual

An OMICs Approach for Assessing the Safety of Single-Walled Carbon Nanotubes in Human Skin and Lung Cells

M.J. Cunningham, M. Shah, C. Lema, S. Magnuson, M. Falduto, L. Balzano and D. Resasco
Houston Advanced Research Center, US

Keywords:
toxicogenomics, gene expression microarrays, proteomics, miRNA

Abstract:
High-throughput OMICs biotechnologies combined with a systems biology approach were used to screen for the toxicity of nanomaterials. Profiling of the macromolecular interactions within human cells was done with mRNA and miRNA expression microarrays (genomics) and two-dimensional gel electrophoresis annotated by mass spectroscopy (proteomics). Primary human epidermal keratinocytes (HEK) and primary human bronchial epithelial cells (NHBE) were exposed in vitro to single-walled carbon nanotubes (SWNT) and other nanoparticulate substances. The data was then analyzed using a four-tiered approach. Statistical analysis of the triplicate arrays performed for each biological sample showed that the microarrays were very reproducible. Hierarchical agglomerative clustering and Principal Components Analysis of the expression data resulted in the greatest variation of the gene expression profiles was between the two cell systems, regardless of the nanomaterial used. Potential biomarkers were identified and several correlated with previous literature references. The final tier was pathway analysis in which the most active genes and proteins were those involved in immune response and membrane integrity and remodeling. By comparing the miRNA, mRNA and protein profiles, a more complete description of the interactions on the macromolecular level within the cell after exposure to nanomaterials can be obtained.

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