Project 4: Measurement and Engineering Solutions to Detect and Prevent N-Nitrosamine Exposure

项目 4：检测和防止 N-亚硝胺暴露的测量和工程解决方案

• 批准号: 10687992
• 负责人: Desiree Plata
• 金额: $ 25.8万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10687992
• 关键词: Acceleration; Address; Air; Biological; Biological Assay; Bioreactors; Biotechnology; Cancer Etiology; Carbon; Carbon Nanotubes; Carcinogens; Cells; Chemicals; Chromatography; Collaborations; Collection; Complex Mixtures; DNA Damage; Data; Data Analyses; Detection; Development; Devices; Dimensions; Disease; Disinfection; Encapsulated; Engineering; Ensure; Environment; Environment and Public Health; Environmental Exposure; Enzymes; Equilibrium; Exposure to; Family; Filtration; Flame Ionization; Food; Gas Chromatography; Genetic Engineering; Genetically Engineered Mouse; Goals; Hazardous Chemicals; Hazardous Substances; Health; Home; Human; In Situ; Ion Exchange; Knowledge; Mass Spectrum Analysis; Measurement; Measures; Methods; Microbe; Mission; Modeling; Molecular; Municipalities; Mutagens; Nanotechnology; Nitrosamines; Nitroso Compounds; Octanols; Performance; Persons; Pharmaceutical Preparations; Phase; Plant Resins; Polymers; Predisposition; Prevention; Probability; Process; Property; Public Health; Research; Research Support; Risk; Safety; Solid; Source; Structure; Superfund; System; Techniques; Technology; Testing; Training; Translational Research; Tribes; United States Environmental Protection Agency; Water; Work; analytical method; animation; carcinogenesis; community engagement; contaminated water; data integration; data management; detector; drinking water; experience; exposed human population; genotoxicity; improved; invention; iterative design; molecular recognition; new technology; novel; novel strategies; prevent; programs; remediation; safety testing; scaffold; sensor; superfund chemical; superfund site; therapy design; toxicant; treatment strategy; water sampling; water treatment

PROJECT SUMMARY/ABSTRACT – PROJECT 4 N-nitroso (-N-N=O) compounds include some of the most powerful chemical mutagens known and encompass a family of chemicals with hundreds of different structures. However, only a handful of N-nitrosamines are routinely measured via EPA Standard Methods, and these methods are not effective at the low levels anticipated to cause health impacts. To overcome this challenge and reduce human exposure, Project 4 seeks to measure and destroy a suite of N-nitrosamines at the point of use in homes, where they are needed most to protect public health and the environment. First, Specific Aim 1 is to develop methods to detect a suite of established and novel N-nitrosamines using multi-dimensional gas chromatography paired with both mass spectrometry (for identification) and flame ionization detection (for quantification with authentic standards or via an effective carbon number concept when authentic standards can be neither synthesized nor purchased). This technique enables estimation of nearly a dozen critical environmental parameters, such that novel molecules detected in complex mixtures will have at-the-ready physicochemical metrics to feed environmental fate models and predict exposure. Water samples will be collected in collaboration with the Community Engagement Core using traditional collection methods as well as novel Recognition-Solid Phase Extraction (R-SPEs) materials that concentrate N- nitrosamines (to be developed in Project 3), and fractions of extracts will be provided to Project 2 for mutagenicity assessment. Knowledge about the levels of NDMA will inform Project 1 so that environmentally relevant levels can be studied for their biological impacts using novel genetically engineered mice that are sensitized to NDMA. In addition, the Data Management and Analysis Core will integrate data for “what” and “how much” with data on biological impact to inform risk. Armed with knowledge of environmental levels of N-nitrosamines, Specific Aim 2 is to develop novel in-home water filtration technologies based on electrochemical processes and molecular recognition with enzymatic destruction. The latter relies on genetically engineered microbes that act as non-living scaffolds for enzymes; as such, it overcomes many classical challenges faced by bioreactors and opens up vast possibilities to leverage advances in biotechnology for long-awaited revolutions in water treatment. Specific Aim 3 will test the degradation products to ensure that they are no longer genotoxic by collaborating with Project 1 to use “Chem-Sense” cells that act as animate detectors of DNA damage. Trainees will drive the research and will be supported by the Research Experience and Training Coordination Core to ensure optimal professional development. In addition, Project 4 will benefit from activities organized by the Administrative Core that ensure close collaborations with other Projects and with the Cores, as well as opportunities for research translation to stakeholders, including people living near the Olin Chemical Superfund Site and the Passamaquoddy Tribe. Via a Systems Approach of interactions and interdependencies, Project 4 will contribute to the protection of human health from hazardous substances.

项目摘要/摘要 – 项目 4 N-亚硝基 (-N-N=O) 化合物包括一些已知且涵盖的最强大的化学诱变剂 具有数百种不同结构的化学物质家族。然而，只有少数 N-亚硝胺 通过 EPA 标准方法进行常规测量，这些方法在预期的低水平下并不有效 造成健康影响。为了克服这一挑战并减少人类接触，项目 4 试图测量 并在家庭使用时销毁一套 N-亚硝胺，因为家庭中最需要它们来保护公众 健康和环境。首先，具体目标 1 是开发方法来检测一套已建立的和 使用多维气相色谱法和质谱法（用于 识别）和火焰离子化检测（使用可靠的标准或通过有效的碳进行定量 当真实的标准既不能合成也不能购买时的数字概念）。该技术使 估计近十几个关键环境参数，以便在复杂的环境中检测到新分子 混合物将具有现成的物理化学指标，以支持环境命运模型并预测暴露情况。 将与社区参与核心合作，使用传统方法收集水样 收集方法以及浓缩 N- 的新型识别固相萃取 (R-SPE) 材料 亚硝胺（将在项目 3 中开发）和提取物的馏分将提供给项目 2 用于致突变性 评估。有关 NDMA 水平的知识将为项目 1 提供信息，以便环境相关水平 可以使用对 NDMA 敏感的新型基因工程小鼠来研究其生物影响。 此外，数据管理和分析核心将把“什么”和“多少”的数据与有关的数据集成起来。 生物影响以告知风险。具备 N-亚硝胺环境水平的知识，具体目标 二是开发基于电化学过程和技术的新型家用水过滤技术 分子识别与酶促破坏。后者依赖于基因工程微生物 作为酶的无生命支架；因此，它克服了生物反应器面临的许多经典挑战 并为利用生物技术的进步实现期待已久的水革命开辟了巨大的可能性 治疗。具体目标 3 将测试降解产物以确保它们不再具有遗传毒性 与 Project 1 合作，使用“Chem-Sense”细胞作为 DNA 损伤的动态探测器。 学员将推动研究，并得到研究经验和培训协调的支持 确保最佳专业发展的核心。此外，项目 4 将受益于 确保与其他项目和核心密切合作的行政核心，以及 向利益相关者（包括居住在奥林化学超级基金附近的人们）提供研究成果转化的机会 遗址和帕萨马科迪部落。通过交互和相互依赖的系统方法，项目 4 将有助于保护人类健康免受有害物质的侵害。