抑制O~6-甲基鸟嘌呤-DNA甲基转移酶活性与肿瘤细胞对亚硝脲药物敏感性关系的研究

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。

The Relationship Between Depletion of O~6-Mehylguanine-DNA Methyltransferase Activity and Sensitivity of Human Tumor Cell Lines to Nitrosourea

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.