CORE--CHEMICAL AND ANALYTICAL

化学和分析核心将为个别研究项目提供支持。核心由两个部分组成：合成实验室和质谱学设施。合成实验室将负责持续提供计划项目已确定需要的特定化合物。Core合成的化合物将被用作定量的标准，用于DNA和蛋白质加合物的体外形成，用于体内给药方案。从合成实验室获得多重标记稳定同位素的标准，对于开发利用质谱学设施对代谢物以及DNA和蛋白质加合物进行超微量分析的同位素稀释方法至关重要。已确定需要合成的化合物的具体类别有：项目1，三环核苷酸、脱氧核苷和脱氧核苷酸；丙二醛和4-羟基非2-烯醛的蛋白质加合物；剂量方案的半胱氨酸连续基础；项目3和8，S-苯基-d5-半胱氨酸和硫代尿酸；项目4，多环芳烃的真菌代谢物和项目5，13C标记的多环芳烃酚。合成实验室还将提供有关结构表征问题的咨询，以及光谱技术在定量和表征问题上的应用。核心专业知识可能对计划项目有用的其他领域是应用结构-活性关系来指导新陈代谢或非酶腐烂产物的分离和表征工作。Core可以使用具有多核和变温能力的500和500 MHz核磁共振波谱仪。核心人员是训练有素的操作员，精通数据采集、整理和解释的所有方面，将满足计划项目的核磁共振需求。可通过核心获得的其他物理表征技术有圆二色X射线结晶学、EPR和FTIR。当质谱学要求超出属于计划项目的设备的能力时，或当需要广泛的方法开发时，质谱学设施将为计划项目提供支持。质谱学设施通过各种质谱学技术进行常规的表征和超痕量分析，并参与开发工作。质谱学设施的主要目标将是开发在线样品净化和分析物预浓缩程序，并将高效液相/质谱仪/质谱仪技术应用于DNA加合物、蛋白质加合物和多环芳烃代谢物的表征。

The Chemistry and Analytical Core will provide support for the individual research projects. The Core consists of two components: the Synthesis Laboratory and the Mass Spectrometry Facility. The Synthesis Laboratory will be responsible for providing, on a continuing basis, specific compounds for which need has been established by the Program Projects. Compounds synthesized by the Core will be used as standards in quantitation, for in vitro formation of DNA and protein adducts for in vivo dosing protocols. The availability of standards multiply labeled with stable isotopes from the Synthesis Laboratory will crucial to the development of isotope dilution methods for ultra-trace analysis of metabolites and DNA and protein adducts by the Mass Spectrometry Facility. Specific classes of compounds for which synthetic needs have been established are: Project 1, tricyclic nucleobases, deoxynucleosides and deoxynucleotides; protein adducts of malondialdehyde and 4-hydroxynon-2-enal; cysteine contual basis for dosing protocols; Projects 3 and 8, S-phenyl-d5-cysteine and mercapturic acid; Project 4, fungal metabolites of PAH and Project 5, 13C-labeled PAH phenoles. Synthesis Laboratory will also be available for consultation on questions involving structural characterizations, and application of spectroscopic techniques to problems of quantitation and characterization. Other areas where Core expertise may be useful to Program Projects are in the application of structure-activity relationships to direct efforts in isolation and characterization of products of metabolism or non-enzymatic decay. The Core has access to 500 and 500 MHz NMR spectrometers with multinuclear and variable temperature capability. Core personnel are trained operators, proficient in all aspects of data acquisition, work-up and interpretation, and will fill the NMR needs of program projects. Additional techniques of physical characterization accessible through the Core are circular dichroism X-ray crystallography, EPR and FTIR. The Mass Spectrometry Facility will provide support for Program Projects when mass spectrometry requirements are beyond the capacity of equipment belonging to Program Projects or when extensive methods development is necessary. The Mass Spectrometry Facility performs characterization and ultra-trace analysis on a routine basis by a variety of mass spectrometric techniques, and is also involved in developmental work. Major objectives of the Mass Spectrometry Facility will be to develop on-line sample clean-up and analyte pre-concentration procedures and to apply HPLC/MS/MS techniques to characterization of DNA adducts, protein adducts and PAH metabolites.