马兜铃酸Ⅰ-DNA加合物合成及电喷雾质谱法检测  

Synthesis and electrospray mass spectrometric analysis of aristolochic acid Ⅰ-DNA adduct

作　　者：季文萱[1] 杨成对[2] 谌贻璞[3] 

机构地区：[1]中国协和医科大学研究生院,北京100730 [2]清华大学分析测试中心,北京100084 [3]中日友好医院肾病中心,北京100029

出　　处：《基础医学与临床》2007年第6期685-689,共5页Basic and Clinical Medicine

基　　金：卫生部属(管)医疗机构临床学科重点项目(2005-2007)

摘　　要：目的建立体外合成及检测马兜铃酸Ⅰ(aristolochic acid I,AAⅠ)-DNA加合物的方法。方法分别采用酶活化法和化学活化法活化AAⅠ后与脱氧腺苷酸反应以合成AAⅠ-DNA加合物,优化各种反应条件,使用液相色谱/串联质谱(LC/MS/MS)法对合成的AAⅠ-DNA加合物进行结构鉴定。结果两种方法均可制得AAⅠ-DNA加合物,质谱负离子采集模式下测得其准分子离子峰m/z621,电喷雾串联质谱(ESI-MS/MS)谱图提供了丰富的结构信息。结论AAⅠ活化后能与腺嘌呤形成AAⅠ-DNA加合物,LC/MS/MS技术能够快速方便准确地检测AAⅠ-DNA加合物。Objective To synthesize aristolochic acid Ⅰ （AA Ⅰ ）-DNA adduct in vitro and to develop a method for the characterization of the adduct. Methods Aristolochic acid （AA） was incubated with 2＇-Deoxyadenosine 5＇- monophosphate in vitro using either enzymatic activation （by xanthine oxidase） or chemical activation （by zinc） to synthesize AA Ⅰ -DNA adduct. The AA Ⅰ -DNA adduct was characterized by the liquid chromatography electrospray ionization/tandem mass spectrometry （LC-ESI-MS/MS）. Results AA Ⅰ -DNA adduct was prepared by two activation methods. Full scan spectra were obtained in the negative ion mode and the quasi-molecular ion peak was m/z 621. Analysis by electrospray ionization/tandem mass spectrometry （ESI-MS/MS） provided useful structural information about AA Ⅰ -DNA adduct. Conclusion AA Ⅰ can bind covalenfly to the exocyclic amino group of purine nucleotides to form AA Ⅰ -DNA adduct. LC/MS/MS is a practical tool to detect AA Ⅰ -DNA adduct.

关 键 词：马兜铃酸 DNA加合物 合成 电喷雾质谱法 

分 类 号：R284[医药卫生—中药学]