Abstract
As the demand for multi-walled carbon nanotube (MWCNT) incorporation into industrial and biomedical applications increases, so does the potential for unintentional pulmonary MWCNT exposure, particularly among workers during manufacturing. Pulmonary exposure to MWCNTs raises the potential for development of lung inflammation, fibrosis, and cancer among those exposed; however, there are currently no effective biomarkers for detecting lung fibrosis or predicting the risk of lung cancer resulting from MWCNT exposure. To uncover potential mRNAs and miRNAs that could be used as markers of exposure, this study compared in vivo mRNA and miRNA expression in lung tissue and blood of mice exposed to MWCNTs with in vitro mRNA and miRNA expression from a co-culture model of human lung epithelial and microvascular cells, a system previously shown to have a higher overall genome-scale correlation with mRNA expression in mouse lungs than either cell type grown separately. Concordant mRNAs and miRNAs identified by this study could be used to drive future studies confirming human biomarkers of MWCNT exposure. These potential biomarkers could be used to assess overall worker health and predict the occurrence of MWCNT-induced diseases.
Highlights
Carbon nanotubes (CNTs) are currently used in diverse industrial and biomedical applications [1,2,3]
Using in vivo mRNA and miRNA data derived from a study of mice exposed to multi-walled carbon nanotube (MWCNT) and sacrificed at 1, 6, and 12 months post-exposure [17] and in vitro mRNA and miRNA data derived from a coculture model of human small airway epithelial cells (SAEC) and human microvascular endothelial cells (HMVEC) exposed to MWCNT for 6 and 24 h [18], this study identified mRNAs with concordant MWCNT-induced expression perturbation in in vivo and in vitro studies, identifying them as potential biomarkers for medical and occupational surveillance in humans
This study identified mRNAs and miRNAs with concordant MWCNT‐induced expression perturbation between in vivo and in vitro settings
Summary
Carbon nanotubes (CNTs) are currently used in diverse industrial and biomedical applications [1,2,3]. MWCNTs delivered to mice by pharyngeal aspiration deposited in the alveolar region of the lungs and translocated to the subpleural space starting one day after exposure [8]. While this may be a normal clearance mechanism for small particles, longer fibers may not be able to properly migrate through the subpleural space [3,9]. While our group has previously found that MWCNT exposure is related to a subset of lung cancer biomarkers in mice following short-term exposure, there are currently no effective biomarkers derived from long-term exposures that are able to detect human lung fibrosis or predict the risk of subsequent lung cancer [12]. The concordant biomarkers identified from this study could be readily tested in human blood samples for monitoring MWCNT-induced disease risk in future studies
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