ENDOGENOUS CARCINOGENS BY MASS SPEC

描述：(改编自申请人的摘要) 内源化学物质形成DNA加合物及其潜在作用 将对癌症的进展情况进行检查。方法将是 用于DNA加合物的结构和定量分析 源自内源性致癌物质。这最终将允许 DNA加合物结构与其潜力之间的关联 在癌症发生中的作用。高效液相色谱-电喷雾质量法 光谱分析将用于修饰的核苷和 核苷酸。然后，这种方法将被扩展到分析 寡核苷酸。以促进结构表征和 DNA加合物的定量，用[13C][15N]DNA的大肠杆菌将是 准备好了。稳定的同位素标记的加合物将被纳入DNA 用化学反应界面质谱仪进行定量。终于 来自体内脂质过氧化模型的内源性DNA加合物和 人类乳腺癌组织样本将被表征和量化。 这将允许对内源DNA加合物的假设进行检验 提供DNA损伤的标记，这种损伤是由内源性途径引起的 致癌。

DESCRIPTION: (Adapted from the applicant's abstract) The relevance of DNA- adduct formation from endogenous chemicals and their potential role in the progression to cancer will be examined. Methodology will be developed for the structural and quantitative analysis of DNA-adduct derived from endogenous carcinogens. This will eventually allow a correlation to be made between DNA-adduct structures and their potential role in carcinogenesis. Liquid chromatography - electrospray mass spectrometry will be employed for analysis of modified nucleosides and nucleotides. This methodology will then be extended to analysis of oligonucleotides. To facilitate structural characterization and quantitation of DNA adducts, E. Coli with [13C][15N] DNA will be prepared. Stable isotope labeled adducts incorporated into DNA will be quantified by chemical reaction interface mass spectrometry. Finally endogenous DNA-adducts from in vivo models of lipid peroxidation and human breast cancer tissue samples will be characterized and quantified. This will allow testing of the hypothesis that endogenous DNA adducts provide a marker of DNA damage that arises from endogenous pathways of carcinogenesis.