Due to their relative chemical stability and ubiquity in the environment, chlorinated organic contaminants such as polychlorinated biphenyls (PCBs) and trichloroethylene (TCE) pose significant health risks and enduring remediation challenges. For example, extensive PCB contamination at the Paducah Gaseous Diffusion Plant, the largest Superfund site in Kentucky, is of major concern for its health consequences. The University of Kentucky Superfund Research Center (UK-SRC) provides a focused transdisciplinary research, training and translation environment to address human health challenges associated with such exposures. Preliminary findings suggest that nutrition-based concepts and exercise can markedly influence the mechanisms of toxicity of chlorinated organics. Indeed, healthful nutrition/nutritional components may provide a platform to develop primary prevention strategies for diseases associated with environmental toxic insults, while also providing the basis for new risk assessment paradigms. Further, novel iron-based, nano-structured capture/sensing and remediation systems based on biomimetic binding domains and functionalized/responsive membrane platforms offer potential for sustainable advances in technical capability for site remediation. The UK-SRC proposes to reduce risk by: 1) developing lifestyle-related modulators of environmental disease and elucidating relevant protective mechanisms, and 2) developing technologically effective and economically efficient methods for capture/sensing and remediation of PCBs. Three biomedical and two environmental science projects, a Research Support Core, and Administrative, Research Translation, Community Engagement and Training Cores collectively advance understanding of toxicant-induced mechanisms of disease, introduce sustainable approaches for remediation and enhance stakeholder and community capacity to act. Biomedical projects focus on models of inflammation and associated changes in redox status and inflammatory cytokines in vascular (Project 1), fetal (Project 2) and adipose (Project 3) tissues with relevance to atherosclerosis, insulin resistance/diabetes and obesity. Environmental science projects employ nanomaterials to create selective PCB-binding domains with high affinity and selectivity for PCBs (Project 4) and a functionalized polymer immobilized membrane platform to support PCB dechlorination (Project 5). All Projects focus on common PCB toxicants. Biomedical scientists, with the Research Support Core, also evaluate byproducts of environmental science projects for unintended effects. Use of PCBs as a model contaminant will advance understanding of inflammatory diseases associated with exposure to persistent chlorinated organic pollutants. Research results will lead to evidence-based multidirectional information/education, technology transfer, training, policy and translational activities via UK-SRC cores. Expected outcomes include positive lifestyle interventions across the lifespan for populations at risk and advanced technical capacity to reduce public health risks.

Public Health Relevance

The proposed research may lead to novel dietary and exercise recommendations, contaminant detection and remediation technology development and policy recommendations for populations at risk to improve the health of people residing near Superfund sites. Outcomes should provide important technology tools and insights for primary stakeholders to use in improving Superfund site risk assessment and management, specifically related to the class of compounds known as chlorinated organics.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Hazardous Substances Basic Research Grants Program (NIEHS) (P42)
Project #
2P42ES007380-17A1
Application #
8649932
Study Section
Special Emphasis Panel (ZES1-LKB-K (S))
Program Officer
Henry, Heather F
Project Start
1997-04-07
Project End
2019-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
17
Fiscal Year
2014
Total Cost
$2,442,381
Indirect Cost
$664,880
Name
University of Kentucky
Department
Veterinary Sciences
Type
Schools of Earth Sciences/Natur
DUNS #
939017877
City
Lexington
State
KY
Country
United States
Zip Code
40506
Murphy, Margaret O; Petriello, Michael C; Han, Sung Gu et al. (2016) Exercise protects against PCB-induced inflammation and associated cardiovascular risk factors. Environ Sci Pollut Res Int 23:2201-11
Perkins, Jordan T; Petriello, Michael C; Newsome, Bradley J et al. (2016) Polychlorinated biphenyls and links to cardiovascular disease. Environ Sci Pollut Res Int 23:2160-72
Platt, Kristen M; Charnigo, Richard J; Shertzer, Howard G et al. (2016) Branched-Chain Amino Acid Supplementation in Combination with Voluntary Running Improves Body Composition in Female C57BL/6 Mice. J Diet Suppl 13:473-86
Wahlang, Banrida; Petriello, Michael C; Perkins, Jordan T et al. (2016) Polychlorinated biphenyl exposure alters the expression profile of microRNAs associated with vascular diseases. Toxicol In Vitro 35:180-7
Pennell, Kelly G; Scammell, Madeleine K; McClean, Michael D et al. (2016) Field data and numerical modeling: A multiple lines of evidence approach for assessing vapor intrusion exposure risks. Sci Total Environ 556:291-301
Hunt, Gary; Stegeman, John; Robertson, Larry (2016) PCBs: exposures, effects, remediation, and regulation with special emphasis on PCBs in schools. Environ Sci Pollut Res Int 23:1971-4
Liu, Dandan; Perkins, Jordan T; Hennig, Bernhard (2016) EGCG prevents PCB-126-induced endothelial cell inflammation via epigenetic modifications of NF-κB target genes in human endothelial cells. J Nutr Biochem 28:164-70
Kania-Korwel, Izabela; Lehmler, Hans-Joachim (2016) Chiral polychlorinated biphenyls: absorption, metabolism and excretion-a review. Environ Sci Pollut Res Int 23:2042-57
Petriello, Michael C; Hoffman, Jessie B; Sunkara, Manjula et al. (2016) Dioxin-like pollutants increase hepatic flavin containing monooxygenase (FMO3) expression to promote synthesis of the pro-atherogenic nutrient biomarker trimethylamine N-oxide from dietary precursors. J Nutr Biochem 33:145-53
Baker, Nicki A; Shoemaker, Robin; English, Victoria et al. (2015) Effects of Adipocyte Aryl Hydrocarbon Receptor Deficiency on PCB-Induced Disruption of Glucose Homeostasis in Lean and Obese Mice. Environ Health Perspect 123:944-50

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