Honors College Thesis
 

Impact of Polycyclic Aromatic Hydrocarbons on Barrier Function Toxicity in 3D Lung Model from Normal and Asthmatic Donor Cells

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https://ir.library.oregonstate.edu/concern/honors_college_theses/2b88qk59h

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  • Polycyclic aromatic hydrocarbons (PAHs) are known to cause adverse health effects in the human lung. Here, we evaluated biomarkers relevant for PAH toxicity in a 3D human primary bronchial epithelial cell (HBEC) model collected from normal and asthmatic donors. We previously found that PAHs decrease cellular barrier function integrity, which can lead to increased permeability, inflammation, and oxidative stress of the airway epithelium and contribute to the pathogenesis of lung disease. Therefore, we hypothesized that normal and diseased cells may have different sensitivity to PAH exposure in inflammation and cell junction-related biomarkers. Primary HBEC were exposed to benzo[a]pyrene (BaP), dibenzo[def,p]chrysene (DBC), and coal tar (CTE). A ROS detection assay found differences in sensitivity for BaP and CTE-exposed cells and no differences for DBC-exposed cells. RNAseq from normal cells treated with concentrations of BaP was used to identify dose-responsive pathways and biomarkers for future comparison with diseased cells. Development and cell adhesion pathways were modelled as a dose-response across BaP exposure using vector quantization and hierarchical clustering. Benchmark dose modelling identified regulation of cytoskeleton rearrangement as the most sensitive pathway. These results suggest that individuals with preexisting conditions may be at greater risk of developing COPD when exposed to air pollutants.
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  • Pending Publication
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  • 2020-06-04 to 2021-01-05

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