体外甲基丙烯酸环氧丙酯-DNA加合物的研究

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）和质谱先进方法分析。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１捉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

Studies on glycidal methacrylate-DNA adducts in vitro

Objective To investigate the types and characteristics of the adducts formed by newly discovered mutagenglycidyl 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.