体外甲基丙烯酸环氧丙酯-DNA加合物的研究  

Studies on glycidal methacrylate-DNA adducts in vitro

作　　者：谭明家[1] 许建宁[1] 李忠生[1] 左瑾[2] 李玉瑞[1] 谢大英[1] 方福德[2] 

机构地区：[1]中国预防医学科学院劳动卫生与职业病研究所毒理学研究室,北京100050 [2]中国医学科学院基础医学研究所

出　　处：《中华劳动卫生职业病杂志》2000年第1期19-21,共3页Chinese Journal of Industrial Hygiene and Occupational Diseases

基　　金：国家自然科学基金!资助项目 (39570 61 5)

摘　　要：目的　探讨新诱变剂甲基丙烯酸环氧丙酯 (GMA)与DNA形成加合物的类型和特性。方法　在体外条件下 ,dAMP、dCMP、dGMP、dTMP及小牛胸腺DNA与GMA发生反应 ,反应产物经紫外光谱、反相高效液相色谱 (RP HPLC)和质谱等方法分析。结果　GMA能与dAMP、dCMP、dGMP及小牛胸腺DNA形成专一性共价结合。已被证实的 1种GMA DNA加合物为N3 甲基丙烯酸 2 羟丙基 脱氧胞嘧啶核苷一磷酸。结论　GMA能与DNA形成加合物 ,其在诱导基因突变致细胞癌变的过程中可能起重要的作用。Objective To investigate the types and characteristics of the adducts formed by newly discovered mutagen[glycidyl methacrylate(GMA)]and DNA in vitro.Methods The dAMP,dCMP,dGMP,dTMP and calf thymus DNA were allowed to react with GMA in vitro.The mixtures were detected by UV and subjected to reversed phase HPLC on Ultrasphere ODS reversed phase column.The reaction products were eluted with a linear gradients of methanol and 10 mmol/L ammonium formate,pH 5.0.The synthesized adducts were then characterized by UV spectroscopy in acid(pH 1.0),neutral(pH 7.2),alkaline(pH 11.0) and by mass spectroscopy.Results That GMA could bind with dAMP,dCMP,dGMP and calf thymus DNA by covalent bond,and the binding sites were specific(such as N 6 of adenine,N 3 of cytosine).Meanwhile,a main GMA DNA adduct in the reaction of GMA with calf thymus DNA was formed as N 3 methacrylate 2 hydroxypropyl dCMP.Conclusion GMA could bind with DNA to form adducts that may play an important role in mutagenesis and carcinogenesis induced by this chemical.

关 键 词：甲基丙烯酸环氧丙酯 DNA加合物 GMA 肿瘤 

分 类 号：R114[医药卫生—卫生毒理学]