DETECTION OF ENDOG AND EXOGEN DERIVED ETHYLENE OXIDE DNA ADDUCTS BY 3H & 14C AM

3H 检测内源和外源衍生的环氧乙烷 DNA 加合物

• 批准号: 7183241
• 负责人: Karen A Brown
• 金额: $ 1.7万
• 依托单位: UNIVERSITY OF CALIF-LAWRNC LVRMR NAT LAB
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-01 至 2006-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7183241
• 关键词: analytical method; biomedical equipment resource; clinical research; mass spectrometry; method development; technology /technique development

DESCRIPTION (provided by applicant): The National Resource for Accelerator Mass Spectrometry (AMS) was established in 1999 to enable biomedical researchers to accurately quantify very low levels of radioisotopes while exploring fundamental issues in biology. In this renewal, we will expand our present capabilities by developing methods to study biochemical pathways and cellular processes at the level of the single cell and small groups of cells, which will allow our collaborators to study the effect of aging in yeast. The Resource will also develop methods to quantify endogenous processes, such as protein and DNA oxidation in higher organisms. This will facilitate the study of inflammatory diseases ranging from atherosclerosis to neurodegenerative disorders to cancer. To further these goals, we will develop a sample presentation technology that will enable the analysis of much smaller samples than can be currently processed, as well as techniques for speciation of biomolecules in such samples. Throughout the tenure of the grant we will continue to provide a resource to the research community that will include service to investigators familiar with AMS, training of investigators in the technology and dissemination of the Resource. Towards these goals, our specific aims are to: 1.) Develop protocols for the online combustion of eluents from separatory instruments and couple the products to a gas accepting ion source to increase the sensitivity of AMS. 2.) Increase the value and information content of AMS measurements by quantitating isotope content in isolates of uniformly isotope-labeled systems or by quantitating derivatized biomarkers of modification or function on specific macromolecules. 3.) Provide quantitation of effector and effect in biological systems using multiple isotopic tracers within sampled materials. We will achieve this by developing a robust and higher throughput process for 3H sample preparation and by leveraging against other funded isotope measurements at the Center for Accelerator Mass Spectrometry (CAMS). 4.) Provide high throughput and precise quantitation for collaborative and service users.

国家加速器质谱资源（AMS）成立于1999年，旨在使生物医学研究人员能够在探索生物学基本问题的同时准确定量极低水平的放射性同位素。在这次更新中，我们将通过开发在单细胞和小细胞群水平上研究生化途径和细胞过程的方法来扩大我们目前的能力，这将使我们的合作者能够研究酵母中衰老的影响。该资源还将开发量化内源性过程的方法，如高等生物体中的蛋白质和DNA氧化。这将促进从动脉粥样硬化到神经退行性疾病到癌症的炎症性疾病的研究。为了进一步实现这些目标，我们将开发一种样品呈现技术，该技术将能够分析比目前可处理的小得多的样品，以及用于此类样品中生物分子形态的技术。在整个任期内的补助金，我们将继续提供资源的研究界，将包括服务的调查人员熟悉AMS，培训的调查人员在技术和传播的资源。为了实现这些目标，我们的具体目标是： 1.）的人。制定分离仪器洗脱液在线燃烧的协议，并将产品与气体接受离子源耦合，以提高AMS的灵敏度。 2.）的情况。通过定量统一同位素标记系统分离物中的同位素含量或定量特定大分子修饰或功能的衍生生物标志物，增加AMS测量的价值和信息含量。 3.）第三章使用多种同位素示踪剂提供生物系统中效应物和效应的定量 在抽样材料中。我们将通过开发一个强大的和更高的吞吐量来实现这一目标。 3H样品制备过程，并利用加速器质谱中心（CAMS）的其他资助同位素测量。 4.）为协作和服务用户提供高通量和精确定量。