Core D: Oxidative Stress Core

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Exposure to fine particles and ultrafine particles in contaminated Superfund soils or produced from thermal treatment of hazardous substances may present health hazards, such as the exacerbation of pulmonary and cardiovascular diseases. The program objective includes determining the involvement of particle-generated reactive oxygen species (ROS) and oxidative stress mechanisms in toxicities observed within target tissues. The Oxidative Stress Core will provide support for Non-biomedical Project 1 and Biomedical projects 2, 4 and 5. Project 1 will determine how the molecular pollutants react with surfaces to form environmentally-persistent free radicals (EPFR) and why they are stabilized. Critical to this effort is elucidating whether the particles themselves redox-cycle to generate ROS. The core will assist with measurements of ROS produced in particle systems in vitro. Project 5 will determine the role of cytochrome P450 in the initiation/exacerbation of particle-induced ROS production. The core will provide support for the measurements of ROS and lipid oxidation in lung microsomes isolated from UFP-treated rats. Projects 2 and 4 will assess the role of UFP in exacerbating ischemia-reperfusion injury in the heart, as well as chronic obstructive pulmonary disease, through mechanisms involving oxidative stress. The core will service these projects by conducting measurements of ROS production and oxidative stress. This proposal describes assays that will be conducted and expertise to be provided. We will utilize the most current technologies, but will also use well-established approaches to measuring the necessary endpoints. Importantly, the core will adapt to the changing needs of the projects and will develop new techniques as necessary. The core is well equipped with the necessary expertise and personnel, and all relevant instrumentation available in the core Leader's laboratory, including spectrophotometers, HPLC, and LC-MS/MS, will be made available to the core. The strengths of the core include the breadth of expertise of the Core Leader and personnel, the accessibility/cooperativity of the core personnel, and the strong collaboration already in place between the core and the described projects.