DETECTION AND CHARACTERIZATION OF PROTEIN AND DNA ADDUCTS BY MASS SPECTROMETRY

该项目涉及利用和继续开发两个方面 将色谱学、电泳学和最先进的质量技术相结合 生物分析鉴定和鉴定所需的光谱方法 为了揭示详细的分子，必须进行结构阐明研究 本计划项目中外来生物毒性和致癌的性质。 这在技术上首次是可行的，可以全面了解 环境条件下同一组织中DNA和蛋白质的加合作用 相关剂量。这一新信息将提供至关重要的洞察 制定切合实际和可靠的方法的根本重要性 风险评估。到目前为止，这个项目已经提供了第一个 激动人心的开创性实验清楚地证明了 AMS检测、凝胶电泳法的协同使用 先进的生物质谱学方法将提供信息 从环境现实性看大分子靶蛋白的同一性 体内暴露剂量。这些信息将直接与 DNA加合物在相同的组织中，从而提供了一个全面的观点 异种生物暴露于人类后改变的细胞结构 超级基金网站。

This project involves both the utilization and continued development and integration of chromatographic, electrophoretic, and the most advanced mass spectrometric methods required in bioanalytical identification and structural elucidation studies necessary to reveal the detailed molecular nature of xenobiotic toxicity and carcinogenesis in this Program project. It is technically feasible for the first time to obtain a complete view of both DNA and protein adduction in the same tissues at environmentally relevant doses. This new information will provide crucial insight of fundamental importance to formulation of realistic and reliable methods of risk assessment. To date this program project has provided the first exciting, pioneering experiments which establish clearly that the collaborative use of the combination of AMS detection, gel electrophoresis and advanced methods of biological mass spectrometry will yield information on macromolecular target protein identity from environmentally realistic exposure doses in vivo. This information will be directly correlated with DNA adducts in the same tissues and thus provide a comprehensive view of the altered cell machinery from xenobiotic exposure to humans from Superfund sites.