A real-time antibody-based field assay to predict containment bioavailability in

一种基于实时抗体的现场测定，用于预测药物中的遏制生物利用度

• 批准号: 8230061
• 负责人: STEPHEN L KAATTARI
• 金额: $ 27.62万
• 依托单位: VIRGINIA INSTITUTE OF MARINE SCIENCE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-12-12 至 2014-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8230061
• 关键词: Adult; Alkylation; Antibodies; Antibody Specificity; Antigens; Aromatic Polycyclic Hydrocarbons; Beds; Biological Assay; Biological Availability; Biosensor; Biota; Carbon; Characteristics; Chemicals; Containment; Creosote; Detection; Development; Dose; Effectiveness; Environment; Environmental Risk Factor; Evaluation; Exposure to; Food Webs; Habitats; Health; Heterogeneity; Human; Laboratories; Lipids; Measurement; Measures; Methods; Modeling; Monitor; Monoclonal Antibodies; National Institute of Environmental Health Sciences; Oysters; Petroleum; Phase; Proteins; Relative (related person); Research Project Grants; Risk; Risk Assessment; Rivers; Route; Sampling; Seafood; Shellfish; Signal Recognition Particle; Silicon Dioxide; Site; Specificity; Surface; System; Technology; Testing; Time; Tissues; Variant; Virginia; Water; aqueous; base; bioaccumulation; chemical property; cost effective; physical property; remediation; sensor; superfund site; uptake

DESCRIPTION (provided by applicant): This NIEHS-SRP research project will use newly developed biosensor technology to rapidly predict how polycyclic aromatic hydrocarbons (PAH) accumulate in seafood exposed to contaminated sediments. Hydrophobic contaminants such as PAH readily accumulate in shellfish, where they pose a significant human health risk when consumed. Lipid partitioning drives bioaccumulation in shellfish but multiple chemical, physical and environmental factors influence bioavailability and tissue concentrations in dynamic natural systems. Because measuring contaminant uptake in biota is time consuming and expensive, models have been developed to predict contaminant fate and disposition. However, temporal variability and heterogeneity of natural habitats make it difficult to reliably predict bioaccumulation for risk assessments from measured sediment concentrations. Ultimately, site-specific measurements are vital to accurately predict contaminant bioavailability and to evaluate the effectiveness of sediment remediation efforts. Recent advances in biosensor technology now allow near real-time measurement of contaminants at sub part per billion concentrations. This project will evaluate, refine and validate an automated, quantitative, monoclonal antibody-based sensor to measure PAH in sediment-associated water. We will validate the biosensor as a predictor of PAH tissue burdens in shellfish, an important route for PAH exposure to humans from contaminated sediments. This will be accomplished through controlled laboratory dosing of oysters. The biosensor will be then be applied in the highly contaminated Elizabeth River, Norfolk, Virginia to assess the effectiveness of ongoing remediation strategies being employed to reduce the human health risks associated with PAH exposure through the food web. Hypotheses 1. Real-time bio-sensor estimates of PAH concentration in aqueous samples (sediment pore water, surface water) rapidly and specifically predict lipid-normalized PAH concentrations in the tissues of native oysters inhabiting PAH-contaminated sites. 2. Biosensor measurements of aqueous PAH concentrations are specific, dose-responsive, correlate directly with tissue concentrations of PAH in dosed oysters and are therefore predictive surrogates of tissue bioaccumulation. 3. Incorporation of mixed analyte beds with differentative antibody specificities for different PAH classes will provide for more accurate discernment of the relative contribution of these different PAHs in the field and laboratory. PUBLIC HEALTH RELEVANCE: Polycyclic aromatic hydrocarbons (PAH) are formed by the combustion of organic matter and they enter the aquatic environment via natural seeps, atmospheric inputs or through spills of petroleum and creosote. Because of their physical properties, PAHs will accumulate in sediments and seafood such as oysters. This research project will develop new antibody-based biosensors to rapidly measure PAHs in the aquatic environment so we can evaluate methods to remediate PAH-contaminated sediments to protect the public from the potential health risks associated with consuming contaminated seafood.

描述（由申请人提供）：该NIEHS-SRP研究项目将使用新开发的生物传感器技术来快速预测多环芳烃（PAH）如何在暴露于受污染沉积物的海鲜中积累。多环芳烃等疏水性污染物很容易在贝类中积累，食用后会对人类健康构成重大风险。脂质分配驱动贝类的生物累积，但多种化学、物理和环境因素影响动态自然系统中的生物利用度和组织浓度。由于测量污染物在生物区系中的吸收是耗时且昂贵的，因此已经开发了模型来预测污染物的归宿和处置。然而，由于自然生境的时间变异性和异质性，很难根据测量的沉积物浓度可靠地预测生物累积性，以进行风险评估。最终，特定地点的测量是至关重要的，以准确地预测污染物的生物利用度和评估沉积物修复工作的有效性。生物传感器技术的最新进展现在允许以十亿分之几的浓度接近实时地测量污染物。该项目将评估、改进和验证一种自动化、定量、基于单克隆抗体的传感器，以测量沉积物相关水中的PAH。我们将验证生物传感器作为贝类中PAH组织负荷的预测器，这是人类从污染沉积物中暴露于PAH的重要途径。这将通过控制牡蛎的实验室剂量来实现。生物传感器将被应用于高度污染的伊丽莎白河，诺福克，弗吉尼亚州正在进行的补救策略，以评估其有效性，以减少人类健康风险与多环芳烃暴露通过食物网。假设1.实时生物传感器估计的PAH浓度在水样（沉积物孔隙水，地表水）迅速，具体地预测本地牡蛎栖息在PAH污染的网站的组织中的脂质标准化的PAH浓度。2.生物传感器测量的水PAH浓度是具体的，剂量响应，直接与组织浓度的PAH在给药牡蛎，因此预测组织的生物积累的替代品。3.将不同抗体对不同PAH类别的特异性混合分析物床合并，将更准确地识别这些不同PAH在现场和实验室中的相对贡献。 公共卫生相关性：多环芳烃（PAH）是由有机物燃烧形成的，它们通过自然渗漏、大气输入或石油和杂酚油的溢出进入水生环境。由于其物理性质，多环芳烃会在沉积物和牡蛎等海产品中积累。该研究项目将开发新的基于抗体的生物传感器，以快速测量水环境中的多环芳烃，以便我们可以评估修复多环芳烃污染沉积物的方法，以保护公众免受与食用受污染海鲜相关的潜在健康风险。