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Superfund Research Program

Oxidative Stress Core (ARRA Funded)

Project Leader: Tammy R. Dugas
Grant Number: P42ES013648
Funding Period: 2009-2011

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Project Summary (2009-2011)

The combustion/thermal processing of organic wastes at Superfund sites leads to the production of airborne organic pollutants and organics associated with fine and ultra-fine particles (UFP). Exposure to these particles may present health hazards, such as the induction or exacerbation of pulmonary and cardiovascular diseases. The overall goal of the program includes determining the involvement of particle generated reactive oxygen species (ROS) and particle-induced oxidative stress mechanisms in toxicities observed within target tissues. The Core will provide support for Dr. Poliakoff’s research and Drs. Varner, Cormier, and Backes. Work described by Dr. Poliakoff will determine the role of nanoclusters in the generation of potentially hazardous air pollutants. Paramount to this effort is elucidating whether the particles are themselves capable of redox-cycling to generate ROS, independent of their interaction with biological systems. The core will thus assist with measurements of ROS produced in particle systems in vitro. Dr. Backes’ project will determine the role of cytochrome P450 in the initiation or exacerbation of particle-induced ROS production. The core will provide support for the measurements of ROS and lipid oxidation is microsome systems treated with UFP. Drs. Cormier and Varner will assess the role of UFP in exacerbating ischemia-reperfusion injury in the heart and lung, as well as chronic obstructive pulmonary disease, through mechanisms involving ROS generation and oxidative stress in the affected tissues. The core will service these projects by conducting measurements of ROS production and endpoints of oxidative stress. The core 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 they become necessary. The core is well equipped with the necessary expertise and personnel, and all relevant instrumentation available in the core director's laboratory, including spectrophotometers, HPLC, and electrospray LC-MS/MS, will be made available to the core. The strengths of the core include the breadth of expertise of the Core Director and personnel, the accessibility/co-operativity of the core personnel, and the strong collaboration already in place between the core and the described projects.

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