NEUROTOXIC SUPERFUND CHEMICALS AND BIOMAKERS

将进行跨学科和相互依存的研究，以调查几类与超级基金相关的化学品，这些化学品对生物系统，特别是哺乳动物的大脑以及发育中的和成人神经系统的其他部分产生毒性或诱变效应。研究将集中在有机氯和与苯有关的溶剂的混合物、其生物降解产物和相关代谢物。三个非生物医学项目将研究这些环境毒物的微生物降解的重要方面。第一个重点是加强地下水的就地厌氧生物降解过程(项目B1)，第二个重点是研究加强这些化学品就地好氧共代谢的方法(项目B2)，第三个重点是调查分解过程中所涉及的微生物群落的性质和要求(项目B3)。四个生物医学项目涉及动物和人类暴露于低浓度这些危险化学物质的检测和对健康的影响。一项研究将开发数据驱动的模型，以检查超级基金衍生的化学物质如何进入人脑(项目A1)；另一项研究将根据结构-活性关系开发神经毒物暴露的敏感生物标记物(项目2)。第三部分将讨论超级基金化学代谢物的神经毒性和神经致癌特性的分子机制(项目A3)。第四项研究将调查化学物质暴露对未成熟大脑发育和适应能力的微妙影响(项目A4)。一个以社区为基础的项目(核心C1)将寻求对暴露于超级基金具有神经毒性潜力的化学品的弱势儿童人群进行神经行为测试。两个研究支持核心提供强大的、最先进的技术支持(核心D1)和下一代质谱学(D3)。外联核心将评估以互联网为基础的教育对偏远地区社区的影响，这些社区在水和其他媒体中接触神经毒物的风险很高。进入培训核心的研究生将从广泛的生物医学和非生物医学研究机会中进行选择，这些机会将为他们提供独特的跨学科培训。总而言之，这项研究计划寻求创新的方法来促进微生物的降解，从而减少对危险化学品的暴露，开发危险的敏感方法来检测它们在环境介质和哺乳动物物种中的存在，并确定它们对发育和成熟的神经系统的潜在不利影响。

Cross-disciplinary and interdependent research will be undertaken to investigate several classes of Superfund-relevant chemicals that exert toxic or mutagenic effects on biological systems, notably the mammalian brain and other parts of the developing and adult nervous system. Research will be focused on mixtures of organochlorine and benzene- related solvents, their biodegradation products and associated metabolites. Three non-biomedical projects will investigate important aspects of the microbial degradation of these environmental toxicants. One focuses on enhancing in situ anaerobic biodegradation processes in groundwater (Project B1), a second examines methods to enhance in situ aerobic co- metabolism of these chemicals (Project B2), and the third investigates the nature and requirements of the microbial community involved in the breakdown process (Project B3). Four biomedical projects address the detection and health impact of animal and human exposure to low concentrations of these hazardous chemical species. One study will develop data-driven models to examine how Superfund-derived chemical enter the human brain (Project A1); another will develop a sensitive biomarker of neurotoxicant exposure based on structure-activity relationships (Project 2). The third will address molecular mechanisms underlying the neurotoxic and neuro-oncogenic properties of Superfund chemical metabolites (Project A3). The fourth will investigate subtle impacts of chemical exposure on the development and adaptability of the immature brain (Project A4). A community-based project (Core C1) will seek to model neurobehavioral tests to disadvantaged pediatric populations exposed to Superfund chemicals with neurotoxic potential. Two Research Support Cores provide powerful, state-of-the-art technical support (Core D1), and next-generation mass spectroscopy (D3). The Outreach Core will assess the impact of Internet-based education on communities in remote locations that are at high risk for exposure to neurotoxicants in water and other media. Graduate students entering the Training Core will select from a wide range of biomedical and non- biomedical research opportunities that will provide them with a unique cross-disciplinary training. In sum, this program of research seeks innovative methods to promote microbial degradation and thereby reduce exposure to hazardous chemicals, to develop hazardous sensitive methods to detect their presence in environmental media and mammalian species, and to define their potential adverse effects on the developing and mature nervous system.