Nutrition and Superfund Chemical Toxicity

描述(由申请人提供) 由于其相对的化学稳定性和在环境中的普遍存在，氯化有机污染物，如多氯联苯(PCBS)和三氯乙烯(TCE)，构成了巨大的健康风险和长期的补救挑战。例如，肯塔基州最大的超级基金工厂帕迪卡气体扩散厂的广泛多氯联苯污染，对其健康后果令人严重关切。肯塔基大学超级基金研究中心(UK-SRC)提供了一个有重点的跨学科研究、培训和翻译环境，以应对与此类暴露相关的人类健康挑战。初步研究结果表明，以营养为基础的概念和运动可以显著影响氯化有机物的毒性机制。事实上，健康的营养/营养成分可以提供一个平台，为与环境有毒侮辱有关的疾病制定初级预防战略，同时也为新的风险评估范式提供基础。此外，基于仿生结合结构域和功能化/响应膜平台的新型铁基纳米结构捕获/传感和修复系统为现场修复技术能力的可持续发展提供了潜力。英国-SRC建议通过以下方式降低风险：1)开发与生活方式有关的环境疾病调节器，并阐明相关的保护机制；2)开发技术上有效和经济高效的方法来捕获/感测和补救多氯联苯。三个生物医学项目和两个环境科学项目，一个研究支助核心，以及行政、研究翻译、社区参与和培训核心共同促进了对毒物引起的疾病机制的了解，引入了可持续的补救方法，并提高了利益攸关方和社区的行动能力。生物医学项目侧重于炎症模型和氧化还原状态的相关变化，以及血管(项目1)、胎儿(项目2)和脂肪(项目3)组织中与动脉粥样硬化、胰岛素抵抗/糖尿病和肥胖相关的炎症细胞因子。环境科学项目利用纳米材料创建对多氯联苯具有高亲和力和选择性的选择性多氯联苯结合域(项目4)和支持多氯联苯脱氯的功能化聚合物固定膜平台(项目5)。所有项目都集中在常见的多氯联苯有毒物质上。生物医学科学家还与研究支持核心一起评估环境科学项目的副产品是否有意想不到的影响。使用多氯联苯作为模型污染物将促进对与接触持久性氯化有机污染物有关的炎症性疾病的了解。研究成果将导致通过UK-SRC核心开展以证据为基础的多方向信息/教育、技术转让、培训、政策和翻译活动。预期结果包括对高危人群的终身积极生活方式干预，以及降低公共卫生风险的先进技术能力。

DESCRIPTION (provided by applicant) 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.