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University of Kentucky

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Superfund Research Program

Superfund Chemicals: Transport, Metabolism and Toxicity

Center Director: Bernhard Hennig
Grant Number: P42ES007380
Funding Period: 1997-2025

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Summary (2000-2005)

The University of Kentucky Superfund Basic Research Program began in 1997 and consists of seven projects (5 biomedical, 2 non-biomedical), a research support core (synthesis), and administrative, training and outreach cores. The goals of this program are: (1) mechanistic investigations of the adverse effects of PCBs and related halogenated compounds; (2) detection of biomarkers of exposure and toxicity; (3) development of highly sensitive and specific sensing systems; and (4) development of advanced remediation techniques and methods of destruction. Three projects are related to PCB effects on phases of carcinogenesis and include studies on: (1) characterizing the activation and genotoxic profile of PCB metabolites; (2) the mechanism of hepatic tumor promotion of PCBs and the role of oxidative stress leading to changes in gene expression; and (3) intercellular adhesion molecules and the mechanism by which PCBs may enhance the development of tumor metastasis. One project examines how PCBs target vascular endothelium and the role of specific dietary fats to potentiate PCB-mediated endothelial dysfunction and specific nutrient interventions that may provide protection against PCB/lipid-mediated atherosclerosis. The final biomedical project is providing an integrated, multidisciplinary, multispecies approach to understanding endpoints and mechanisms of action of endocrine disrupting PCBs. One non-biomedical project is developing optical and electrochemical biosensing systems for PCBs based on recombinant bacteria that incorporate catabolic pathways for PCBs, along with the expression of reporter genes, and mammalian and yeast systems that couple reporter gene expression with binding of the contaminant to the aromatic hydrocarbon receptor. The second non-biomedical project is investigating dehalogenation as a remediation strategy for chlorinated organics. Specifically, the role of the reductive agent morphology on optimizing destruction of chlorinated organics is being studied.

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