摘要
80％以上的肿瘤细胞为O^6-甲基鸟嘌吟-DNA甲基转移酶(O^6-MT)活性较高的Mer^+型,能够修复亚硝脲药物(NU)造成的DNA烷化损伤,对NU不敏感。本实验证明,用0.75,0.50和0.25mmol/L甲基亚硝脲(MNU)分别处理Mer^+型的HeLaS3,SMMC-7721和表现Mer^-型特征的Cc801,均能明显降低细胞中O^6-MT活性,从而显著提高了三种细胞对嘧啶亚硝脲和双氯乙亚硝脲的敏感性,提示降低O^6-MT活性是使用NU对Mer^+型肿瘤进行有效治疗的前提。
More than 80% of human tumor cell lines, showing high O6-methylgu-anine-pNA methyltransferase (O6-MT) activity (Mer+), are proficient in the repair of alkylated DNA and are thus resistant to nitrosourea.In this study, pretreatment of two Mer+ human cell lines (HeLa S3, SMMC-7721) and the Mer- characterised Cc801, with 0.75, 0,50, and 0.25 mmol/L methylnitrosourea (MNU) respectively, apprarently deplete O6-MT activity in these cell lines without obvious toxic effect on cell survival.As observed by colony forming assays, MNU pretreatment causes a dramatic increase in the sensitivity of these cell lines to ACNU and BCNU.It suggested that the depletion of O6-MT activity be the prerequisite for effective treatment of Mer+ human tumors by nitrosourea.
基金
国家自然科学基金
关键词
肿瘤
亚硝脲
O^6-MT
药物疗法
O6-methylguanine-DNA methyltransferase
Cancer chemotherapy
Methylnitrosourea, ACNU
BCNU
