The MIT Superfund Research Program: A Systems Approach for the Protection of Human Health from Hazardous Chemicals

项目摘要/摘要--总体 N-亚硝胺是一类危险化学品，是已知的最具诱变性的化学品之一， 在动物模型中，许多都是潜在的致癌物质。居住在马萨诸塞州威尔明顿的人们担心N- 亚硝胺，因为附近的奥林有超过2000万加仑被N-亚硝胺污染的废物 化学超级基金网站，污染环境，使他们的井水无法饮用。这个 PassamAquoddy部落也对N-亚硝胺感到担忧，因为他们的水含有大量的 众所周知，有机材料和氯胺的使用可以产生N-亚硝基二甲胺。具体目标1是 制造和测量。利用智能手机的创新的、基于光的化学传感器将被创造和使用 让公民科学获得有助于环境保护局清理工作的信息 (美国环保署)。以细胞微阵列技术为基础的创新的、高通量的“生物传感器”将被创造出来 用于测试N-亚硝胺对已知与癌症有关的健康影响的后果 风险。为了更深入地了解疾病，一种通过基因工程改造的“煤矿里的金丝雀”小鼠模型将 被用来揭示长期低剂量暴露导致突变和有害生物的可能性 回应。具体目标2是通过预测和预防疾病来保护人类健康。通过 集成多组学数据(由数据管理和分析核心[DMAC]提供支持)，机械性 知识将推动预测性生物标志物的发展，这些标志物可用于开发预防 疾病。将研究益生菌抑制N-亚硝胺诱发癌症的潜力。此外，小说 将制造通过电化学和生化销毁来销毁N-亚硝胺的装置。重要的是 风险评估依赖于工程师和生物学家的知识。因此，DMAC将形成关键的 通过合并跨学科数据流来整合作用，以评估特定水样的风险。特定的 目标3是通过整合麻省理工学院SRP并与麻省理工学院以外的合作伙伴进行整合，最大限度地发挥社会影响。 与社区合作将允许收集将告知风险的环境数据。通过双向 在交流方面，社区成员还将受益于新颖的实践教学工具包，而麻省理工学院SRP 成员将受益于了解社区的观点和关注的问题。麻省理工学院SRP的传播 知识和技术也将通过继续加强麻省理工学院之间的关系来实现 SRP和地方、州、部落和政府机构，包括受影响最大的社区成员 被N-亚硝胺污染。所有这些工作都将通过仔细的协调和形式化而成为可能 翻译机会(由行政核心使之成为可能)，并通过不断改进 培训机会，不仅为研究提供动力(通过研究经验和培训实现 协调核心[RETCC])，但也有助于确保受训人员继续作为负责任的领导者做出贡献 他们能够利用跨学科研究对公共卫生产生强大的影响。

PROJECT SUMMARY/ABSTRACT – OVERALL N-Nitrosamines are a family of hazardous chemicals that are among the most mutagenic chemicals known, and many are potently carcinogenic in animal models. People living in Wilmington, MA, are concerned about N- nitrosamines because there are over 20 million gallons of N-nitrosamine-contaminated waste at the nearby Olin Chemical Superfund Site, contaminating the environment and rendering their well water undrinkable. The Passamaquoddy Tribe is also concerned about N-nitrosamines, because their water contains high levels of organic material and the use of chloramine is known to create N-nitrosodimethylamine. Specific Aim 1 is to make and measure. Innovative, light-based chemical sensors that exploit smartphones will be created and used for Citizen Science to gain information that will help to inform cleanup by the Environmental Protection Agency (EPA). Innovative, high-throughput `animate sensors,' based on cell-microarray technology, will be created and used to test the consequences of N-nitrosamines on health-related impacts known to be associated with cancer risk. To understand disease more deeply, a genetically engineered “canary in the coal mine” mouse model will be used to reveal the potential for long-term low-dose exposure to cause mutations and deleterious biological responses. Specific Aim 2 is to protect human health via prediction and prevention of disease. By integrating multi-omics data (fueled by the Data Management and Analysis Core [DMAC]), mechanistic knowledge will propel the development of predictive biomarkers that can be used to develop methods to prevent disease. The potential for probiotics to suppress N-nitrosamine-induced cancer will be studied. In addition, novel devices will be created to destroy N-nitrosamines via electrochemical and biochemical destruction. Importantly, risk evaluation depends on knowledge from both engineers and biologists. The DMAC will thus form a critical integrating role by merging transdisciplinary data streams to evaluate risk for specific water samples. Specific Aim 3 is to maximize societal impact via integration within the MIT SRP and with partners outside of MIT. Partnering with the community will allow collection of environmental data that will inform risk. Via bidirectional communication, community members will also benefit from novel, hands-on teaching kits, while MIT SRP members will benefit from learning about community perspectives and concerns. Dissemination of MIT SRP knowledge and technologies will also be achieved via continued strengthening of relationships between the MIT SRP and local, state, Tribal and governmental agents, including community members who are most impacted by N-nitrosamine contamination. All of this work will be made possible by careful coordination and formalization of translation opportunities (made possible by the Administrative Core), and by continuous improvement of training opportunities that not only fuel the research (made possible by the Research Experience and Training Coordination Core [RETCC]), but also help to ensure that trainees go on to contribute as responsible leaders who are able to leverage cross-disciplinary research in order to have a powerful impact on public health.