dc.identifier.uri | http://hdl.handle.net/11401/77656 | |
dc.description.sponsorship | This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. | en_US |
dc.format | Monograph | |
dc.format.medium | Electronic Resource | en_US |
dc.language.iso | en_US | |
dc.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
dc.type | Dissertation | |
dcterms.abstract | Reactive Oxygen Species (ROS) are vital to the normal functioning of the immune system in the human body. However, when a foreign material enters the system the highly regulated balance between pro- and anti-oxidants can be disrupted, especially if the material itself can generate ROS. One way a material can generate ROS is through Fenton chemistry. The hypothesis that Fenton chemistry is an important factor in many exposure related diseases is experimentally tested using an array of complementary acellular and cellular in vitro techniques. The acellular experiments focused on determining the particle-derived formation of ROS upon dispersion in aqueous solutions, under biologically applicable conditions. The cellular experiments consisted of challenging human lung epithelial cells (A549 cell line) with varying amounts of earth and synthetic material in order to determine an inflammatory stress response (ISR). Defined as the cellular upregulation of ROS normalized by cellular viability, the ISR is a gauge of particle toxicity. The protocol is designed to not only capture the effect that low and high exposures have on cells, but also the effect of particle exposure on cells over time. This dissertation underlines the necessity of using an interdisciplinary approach to determine the impact of geomaterials on human health and highlights the role that a material's structure, chemistry, oxidation state and complexity have in pathogenesis. The results reported in this dissertation not only suggest that Fenton chemistry plays a role in inflammation-based diseases but also highlights the deleterious nature of ferrous minerals, pyrite in particular. The initial acellular oxidative dissolution studies demonstrated pyrite's ability to generate ROS and its relatively short biopersistence (a two micron pyrite particle will dissolve in about three years). Taken together it begins to explain the correlation between the prevalence of Coal Workers' Pneumoconiosis (CWP) among miners who are exposed to coal with high pyritic sulfur contents and why no pyrite is found in the autopsied lungs of these deceased miners. The extreme ISR of human lung epithelial cells exposed to pyrite (1,100 fold higher than the control) compared to standard reference materials (ISR generated by San Joaquin NIST soil with baseline trace element concentrations is 3 fold higher than the control and Montana NIST soil with highly elevated trace element concentrations is 11 fold higher than the control) confirms the inflammatory nature of pyrite and experiments with coals containing variable pyritic sulfur contents support the correlation with the prevalence of CWP in miners. While an elevated ISR is generally attributable to both an upregulation of cellularly derived ROS and low cellular viability, the drivers for toxicity are complex. The design of the ISR experiments not only allowed for the base determination concerning a material's toxicity, it also allowed for different pathways of toxicity to be observed, highlighting the ability of a material to upregulate cellular ROS (indicator of future apoptosis) and/or generate necrotic cellular death. Subsequent experiments concerning the toxicity of mineral ores, Fenton metals, and natural dust samples underscore the importance of this integrated approach. Copper-sulfide ore minerals generate extreme ISR values (chalcopyrite rivaled pyrite at 860 fold higher than control), which resulted from both an upregulation of ROS and necrotic cell death. However, the ISR generated by the lead sulfide ore mineral galena (32 fold greater than the control) stems solely from necrotic cell death. Conversely, the ISR generated by manganese-doped goethite is predominately due to a cellular upregulation in ROS. There are two factors that modulate a material's toxicity, the reactivity of the material and its components and total particle burden. Based on our research, a material that is considered inert will generate an ISR value that is around 2 to 4 fold greater than the control. This response is based solely on the presence of the foreign particles. This process is evidenced by our research into the cause of lung illnesses among soldiers returning from Iraq. While the ISR experiments were able to narrow the dusts' minimal inflammatory nature to the carbonate phases and associated elements (e.g., manganese), the stress is only achieved after increasing the particle loading by more than a factor of 10 (over typical ISR exposure values). Given the extremely high PM2.5 concentrations in the Greater Middle East, the origin of the toxicity is likely predominately due to " particle overload," which causes impairment or cessation of the body's main defense mechanisms, phagocytosis and efferocytosis. | |
dcterms.available | 2017-09-20T16:53:13Z | |
dcterms.contributor | Tsirka, Styliani | en_US |
dcterms.contributor | Schoonen, Martin A.A. | en_US |
dcterms.contributor | Rasbury, Troy | en_US |
dcterms.contributor | Reeder, Richard | en_US |
dcterms.contributor | Simon, Sanford. | en_US |
dcterms.creator | Harrington, Andrea Dawn | |
dcterms.dateAccepted | 2017-09-20T16:53:13Z | |
dcterms.dateSubmitted | 2017-09-20T16:53:13Z | |
dcterms.description | Department of Geosciences. | en_US |
dcterms.extent | 141 pg. | en_US |
dcterms.format | Application/PDF | en_US |
dcterms.format | Monograph | |
dcterms.identifier | http://hdl.handle.net/11401/77656 | |
dcterms.issued | 2015-08-01 | |
dcterms.language | en_US | |
dcterms.provenance | Made available in DSpace on 2017-09-20T16:53:13Z (GMT). No. of bitstreams: 1
Harrington_grad.sunysb_0771E_11360.pdf: 11676614 bytes, checksum: e35e2e182a93e688aa8d9006c5cebee1 (MD5)
Previous issue date: 2013 | en |
dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
dcterms.subject | Coal Workers' Pneumoconiosis, Fenton Chemistry, Mineral Toxicity, Occupational Hazards, Reactive Oxygen Species | |
dcterms.subject | Toxicology | |
dcterms.title | Fenton Chemistry and Disease - The Role of Particle-Derived Reactive Oxygen Species in Pathogenesis | |
dcterms.type | Dissertation | |