Research Project 1

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PCBs: Metabolism, Genotoxicity and Gene Expression in Vivo

The goal of Project 1 is the identification of targets and mechanisms of toxicity that will form a
basis for our understanding of PCBs risks to human health and their amelioration. Special emphasis is
given to school air PCBs.

The broad differences in the physical structures of PCBs and their metabolites presents a plethora of possible mechanisms of toxicity, including metabolically driven and receptor-driven targets and toxicities. Therefore, our studies include investigations of the redox environment, of receptor driven effects in organs, of gene expression and maromolecular changes, and finally exploration of the changes in humans exposed to PCBs.

We will focus on metal homeostasis and oxidative stress, redox enzymes and gene expression changes in liver and lung. Dietary supplements will be examined for chemoprotection. In collaboration with Project 7, we will examine the toxicity and changes in the redox networks of liver and lung tissue upon chronic inhalation of an airborne PCB mixture in an animal model.

We will analyze blood and urine from Project 6 participants in East Chicago and Columbus Junction for indications of oxidative stress, metabolic disturbance, and DNA damage and correlate our findings with exposures and PCB body burden.

The ultimate goal of Project 1 is to identify protection methods for exposed populations.

  • Project Leader: Larry Robertson, PhD, MPH

    Dr. Robertson oversees and coordinates the entire project and designs, plans and supervises the proposed experiments listed. He will be responsible for analyzing and publishing the results of the proposed experiments.

  • Co-Project Leader: Gabriele Ludewig, PhD

    Dr. Ludewig is trained as a toxicologist (cyto-and genotoxicity, cell culture etc.) and has spent three years as a postdoctoral scholar applying methods of molecular biology and yeast genetics to study the mechanisms of toxicity and resistance of the drug Pentamidine.

  • Co-Project Leader: Garry Buettner, PhD

    Dr. Buettner is Professor of Radiation Oncology/Free Radical and Radiation Biology and
    Director of the ESR Facility at the University of Iowa College of Medicine. He has over twenty years of research experience in free radical biology.

  • Dr. Kai Wang