CORE--ANALYTICAL CHEMISTRY/AMS

分析核心是一个中心资源，旨在促进开发和应用强大的分析方法，以解决超级基金项目各组成部分遇到的关键问题。分析核心的总体目标是促进研究和开发分析技术，以解决检测、评估、评估和减少危险化学品暴露及相关人口健康风险的问题。分析核心提出了三个具体目标：1)使用色谱和光谱技术为超级基金计划中的项目提供分析支持。2)使用加速器质谱仪(AMS)和核显微镜提供对危险物质的高灵敏度分析。3)在多肽化学方面提供支持，包括多肽的气相序列分析和LC-MS分析。目标1的实现将包括通过应用免疫亲和纯化加强化学暴露相序列的开发，通过应用免疫亲和纯化开发化学暴露的LC/MS/MS生物标记物，以及开发以LC/MS/MS为驱动的多维代谢物图谱。还将通过在多项目毒性鉴定评价研究(TIES)中履行分级和结构鉴定职责，为从复杂混合物中鉴定有毒物质提供支助。分析核心将开发真空紫外电离质谱仪器，用于灵敏地检测和定量焚烧过程中产生的与人体健康风险有关的有毒金属氧化物和多卤代芳香烃。目标2将利用AMS的阿托莫尔(即10-18)敏感性，改进对环境中危险化学品对人类健康的风险分析。用低水平的14C、36Cl和其他长寿命同位素标记的化学物质将通过生态系统、动物模型和人类进行定量追踪。利用高效液相色谱分离，可以确定包括蛋白质和DNA在内的这些化学物质的动力学、转化和最终的生物靶标。AMS还将用于提高已开发的免疫化学生物标记物检测的灵敏度。核微探针分析还将用于量化过滤器或组织环境中同样可能导致疾病状态的重金属的位置、分布和数量。目标3将解决与危险化学品暴露相关的蛋白质识别和修饰问题。高效液-质联用、酶消化和多肽图谱将是实现这一目标的主要工具。核心科学家将教育超级基金的研究科学家全系列分析技术的使用和价值。

The Analytical Core is a central resource designed to facilitate the development and application of powerful analytical methods to solve key problems encountered by the components of the Superfund Project. The general goals of the Analytical Core are to facilitate research and develop analytical technologies that address the detection, assessment, evaluation and reduction of hazardous chemical exposure and the associated population health risks. There are three specific aims proposed by the Analytical Core: 1) Provide analytical support for projects in the Superfund Program using chromatographic and spectroscopic techniques. 2) Provide high sensitivity analysis of hazardous substances using Accelerator Mass Spectroscopy (AMS) and Nuclear Microscopy. 3) Provide support in peptide chemistry including gas phase sequencing and LC-MS analysis of peptides. Accomplishment of Aim 1 will include enhanced development of phase sequencing of chemical exposure through application of immunoaffinity purification and development of HPLC/MS/MS biomarkers of chemical exposure through application of immunoaffinity purification and development of HPLC/MS/MS driven multi-dimensional metabolite profiling. Support will also be provided by for toxic substances identification from complex mixtures by performing fractionation and structural elucidation duties in multi-project toxicity identification complex mixtures by performing fractionation and structural elucidation duties in multi-project toxicity identification evaluation studies (TIEs). The Analytical Core will develop vacuum ultraviolet ionization mass spectroscopy instrumentation for the sensitive detection and quantitation of toxic metal oxides and polyhalogenated aromatic hydrocarbons produced during incineration and linked to human health risks. Aim 2 will utilize the attomole (i.e. 10-18) sensitivity of AMS to improve the analyses of risks to human health due to hazardous chemicals in the environment. Chemicals labeled with low levels of 14C, 36Cl, and other long-lived isotopes will be traced quantitatively through ecosystems, animal models, and humans. Using HPLC separation the kinetics, the transformations and final biological targets of these chemicals including proteins and DNA will be identified. AMS will also be used to enhance the sensitivity of developed immunochemical biomarker detection. Nuclear Microprobe analyses will also be used to quantify the location, distribution, and amount of heavy metals from the environment of filters or tissue that can similarly lead to diseased states. Aim 3 will address the questions of protein identify and modification associated with hazardous chemical exposure. HPLC/MS/MS, enzymatic digestion and peptide mapping will be the primary tools for the accomplishment of this aim. The Core scientists will educate Superfund research scientists in the use And value of the full array of analytical techniques.