铂类络合物引起的DNAO6-AGT的耗竭及染色体损伤

被引:2
作者
王龙贵
刘晓梅
范培东
籍秀娟
机构
[1] 中国医学科学院药物研究所,中国医学科学院药物研究所,中国医学科学院药物研究所,中国医学科学院药物研究所北京,北京,北京,北京
关键词
宁辛铂; Mer细胞; DNA鸟嘌呤O6-烷基转移酶; 染色体损伤;
D O I
10.16438/j.0513-4870.1991.08.001
中图分类号
学科分类号
摘要
本文测定了KB,CHL,HL-60和L1210细胞DNA鸟嘌呤O6-烷基转移酶(O6-AGT)活性。结果表明,KB细咆有较高的O6-AGT活性,系Mer+细胞。而CHL,HL-60和L1210细胞的O6-AGT活性低,属于Mer-细胞。在此基础上我们观察了顺铂(DDP)、宁辛铂(樟脑胺氯乙酸铂,CCP)和碳铂(JM-8)对KB(Mer+)细胞O6-AGT的影响及Mer+和Mer-细胞的杀伤及微核的诱发作用。结果表明,三种络合物在等毒性浓度下对O6-AGT耗竭程序是CCP>DDP>JM-8,但这种耗竭与杀细胞作用无明显相关性而与微核诱发作用相关。此结果提示铂类络合物对DNA鸟嘌呤O6的损伤可能是其致痛致突变的原因之一。
引用
收藏
页码:561 / 566
页数:6
相关论文
共 8 条
[1]  
Induction and repair of DNA cross-links in Chinese hamster ovary cells treated with various platinum coordination compounds in relation to platinum binding to DNA, cytotoxicity, mutagenicity and antitumor activity. Plooy ACM,et al. Cancer Research . 1984
[2]  
DNA cross-linking and cytotoxicity induced by cisdiamine-dichloroplatinum (Ⅱ)in human normal and tumor cells. Laurent,G. Cancer Research . 1981
[3]  
Inactivation of O~6-alkylguanine-DNA alkyltransferase in HeLa cells by cisplatin. Wang LG,Setlow RB. Carcinogenesis . 1989
[4]  
DNA-protein, DNA interstrand cross-links induced by camphoramine chloroacetic platinum in vitro. Wang LG,Zeng H. Acta Pharmacological Sinica . 1989
[5]  
Properties and assay of mammalian O~6-alkyltransferase. Pegg AE,Dolan ME. Pharmacology and Therapeutics . 1987
[6]  
Direct assay for O~6-methylguanine-acceptor protein in cell extracts. Waldstein EA,et al. Analytical Biochemistry . 1982
[7]  
Comparison of O~6-alkylguanine-DNA alkyltransferase activity based on cellular DNA content in human, rat and mouse tissues. Gerson SL,et al. Carcinogenesis . 1986
[8]  
A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Bradford MM. Ibis . 1976