Type of Document Dissertation Author Murphy, Jr., Gleeson Author's Email Address firstname.lastname@example.org URN etd-07082007-222724 Title Responses of Respiratory System Cells in Vitro and in Vivo to PetrochemicalCombustion-Derived Ultrafine Particles Degree Doctor of Philosophy (Ph.D.) Department Comparative Biomedical Sciences (Veterinary Medical Sciences) Advisory Committee
Advisor Name Title Arthur L. Penn Committee Chair Daniel B. Paulsen Committee Member Steven A. Barker Committee Member William G. Henk Committee Member Christopher D. White Dean's Representative Keywords
- polynuclear aromatic hydrocarbons
Date of Defense 2007-05-30 Availability unrestricted AbstractEnvironmental contamination with airborne particles has been a human health concern
for many years. Epidemiologic studies in urban communities have linked ambient particle
exposure to various health effects, including chronic obstructive pulmonary disease, lung cancer, and several cardiovascular disease conditions. The pathogenesis of these conditions with respect to ambient particle exposure is complex because ambient particles are complex in composition. The particles vary greatly in origin, size, surface area, and elemental composition; and a given particle type, such as those generated by petrochemical (gasoline, diesel, industrial substrate) combustion, may be coated with many other compounds, including polynuclear aromatic hydrocarbons (PAHs).
Our laboratory group had previously characterized the generation of PAHs from incomplete combustion of the high volume petrochemical 1,3-butadiene (BD) and briefly
described the biological effects of BDís incomplete combustion product, butadiene soot (BDS), in vitro. The studies presented here represent a continuation of these initial studies, where we first characterize BDS with respect to particle size distribution and assembly, PAH composition, and elemental content of BDS ultrafine particles. We also describe in vitro assays demonstrating that BDS ultrafine particles can transport and transfer adsorbed organic constituents directly to target respiratory cells, without uptake of the particles by the cells. Next, we demonstrate that combustion-derived PAHs adsorbed onto BDS particles are concentrated in lipid droplets of respiratory system cells and that, in vitro, these PAHs activate xenobiotic metabolism pathways. We also present an in vivo analysis of
bronchoalveolar lavage fluid (BALF) with inflammatory cell infiltrates, histopathological evidence of inflammation and particle retention, and gene expression analysis revealing upregulation of several cytokines and AhR-responsive biotransformation enzymes. Finally, we present ultrastructural evidence that BDS particles can be internalized by bronchoepithelial cells in vitro and phagocytosed by alveolar macrophages in vivo. These studies were designed to characterize and promote BDS as both a model mixture and a real-life example of a petrochemical product of incomplete combustion with the potential both for environmental contamination and for contributing to health problems.
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