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: 10351935
• 负责人: Desiree Plata
• 金额: $ 24.96万
• 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/10351935
• 关键词: 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; Malignant Neoplasms; 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; Prevention; 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; base; community engagement; contaminated water; data management; detector; drinking water; experience; exposed human population; genotoxicity; improved; 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-硝基（-n-N = O）化合物包括一些已知和包含的最强大的化学诱变剂 一个具有数百种不同结构的化学品家族。但是，只有少数N-硝基胺是 通常通过EPA标准方法测量，这些方法在预期的低水平上无效 引起健康影响。为了克服这一挑战并减少人类暴露，项目4试图衡量 并在房屋使用点销毁一套N-硝基胺，最需要保护公众 健康与环境。首先，具体目的1是开发检测一套已建立和的方法 使用多维气相色谱法与两种质谱配对的新型N-亚硝胺（用于 识别）和火焰电离检测（用于使用真实标准或通过有效碳进行定量 数字概念何时既无法合成也无法购买，也无法购买。这种技术可以实现 估计近十几个临界环境参数，以便在复合物中检测到的新分子 混合物将具有准备就绪的物理化学指标，以供应环境脂肪模型并预测暴露。 水样将与传统的社区参与核心合作收集 收集方法以及新型识别固定相提取（R-SPE）材料，这些材料集中n- 硝基胺（将在项目3中开发），并将提取物的分数提供给项目2的诱变性 评估。关于NDMA水平的知识将告知项目1，以便与环境相关的水平 可以使用对NDMA敏感的新型基因工程小鼠的生物学影响进行研究。 此外，数据管理和分析核心将将“什么”和“多少”的数据与数据集成 生物学影响以告知风险。具有N-亚硝基胺的环境水平的知识，具体目的 2是基于电化学过程和 分子识别伴有酶破坏。后来依赖于一般设计的微生物 充当酶的非生存支架；因此，它克服了生物反应器面临的许多古典挑战 并为期待已久的水的革命开辟了巨大的可能性，以利用生物技术的进步 治疗。特定目标3将测试降解产物，以确保它们不再是遗传毒素 通过与项目1合作使用“化学态”细胞，该细胞充当DNA损伤的动画探测器。 学员将推动研究，并将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将受益于组织的活动 确保与其他项目和核心进行密切合作的行政核心以及 研究翻译给利益相关者的机会，包括居住在Olin Chemical Superfund附近的人们 地点和帕萨夸迪部落。通过互动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危险物质。