ENDOGENOUS CARCINOGENS BY MASS SPEC

描述：（改编自申请人摘要） 内源性化学物质的DNA加合物形成及其潜在作用 在癌症发展过程中的作用方法将 用于DNA加合物的结构和定量分析 来源于内源性致癌物。这将最终使一个 在DNA加合物结构和它们的潜力之间进行关联 在致癌作用中的作用。液相色谱-电喷雾质谱 光谱法将用于分析修饰的核苷， 个核苷酸这种方法将扩展到分析 寡核苷酸 为了便于结构表征和 DNA加合物的定量，E.含[13 C][15 N] DNA的大肠杆菌将 制备掺入DNA的稳定同位素标记加合物将被 通过化学反应界面质谱法定量。最后 来自体内脂质过氧化模型的内源性DNA加合物， 将对人乳腺癌组织样品进行表征和定量。 这将允许测试内源性DNA加合物 提供了一种DNA损伤的标志物，这种DNA损伤是由内源性途径引起的， 致癌作用

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.