体内GMA-DNA加合物的研究

Study on GMA-DNA Adducts in vivo

目的 在整体动物水平验证大鼠不同器官是否能形成甲基丙烯酸环氧丙脂(GMA)-DNA加合物。方法 大鼠灌胃给予GMA(31.25～250mg/kg体重),14d后,用32P-后标记法分析肝、肾、外周血白细胞和睾丸中GMA-DNA加合物的形成状况。结果 不同组织器官中形成类型不同、数量不等的GMA-DNA加合物。其中白细胞有4种,肝和肾均有3种,睾丸有1种。当GMA剂量为0～125mg/kg体重时,GMA-DNA加合物的形成量随GMA剂量的增加呈上升趋势,且在所检测组织器官中,其形成量的次序为:肾>肝>白细胞>睾丸。加合物N3-甲基丙烯酸-2羟丙基-脱氧胞嘧啶核苷一磷酸(N3-methacrylate-2-hydroxypropy1-dCMP)存在于肝、肾和白细胞中而不存在于睾丸中。结论 具有亲电子集团的GMA能与DNA带负电荷中心反应形成GMA-DNA加合物。

To investigate whether glycidly mechacrylate (GMA DNA) adducts can be produced in various organs of rat in vivo. Methods Rats divided into 5 groups were orally administrated with mutagen, GMA 31 25, 62 5, 125, 250 mg/kg respectively for 14 days. DNA adducts produced in liver, kidney, white blood cells and testis had been analyzed by nuclease P1 mediated 32 P postlabelling method. Results Several GMA DNA adducts were formed in various organs (in white blood cells, 4 types, liver and kidney, 3 types and testis 1 type). The amount of GMA DNA adducts increased with GMA dosage within 0~125 mg/kg dosages, degree of the overall level of GMA DNA adducts in various organs were kidney>liver>white blood cells>testis. N 3 methacrylate 2 hdroxypropyl deoxycytidine monophosphate was found in kidney, liver and white blood cells. Conclusions GMA with electrophilic group could react with negatively charged centers on DNA and form GMA DNA adducts.