Matijasevic Z, Bodell W J, Ludlum D B
Department of Pharmacology, University of Massachusetts Medical School, Worcester 01655.
Cancer Res. 1991 Mar 1;51(5):1568-70.
Extracts of a glial cell line (SF-126) which is sensitive to the cytotoxic effect of the haloethylnitrosoureas and of a cell line (SF-188) which is resistant to these agents have been tested for their ability to release methylated bases from a DNA substrate which has been modified with [3H]dimethyl sulfate. In comparison with the sensitive cell line, extracts from the resistant cell line have 2-3-fold higher enzymatic activity. High performance liquid chromatography profiles of the bases which are released by these extracts show that the activity is specific for 3-methyladenine, suggesting that the resistant cells contain elevated levels of 3-methyladenine DNA glycosylase. Previous studies have shown that these cells also contain elevated levels of O6-alkylguanine-DNA alkyl-transferase, suggesting that both enzyme activities may be involved in the resistance of this cell line to the haloethylnitrosoureas.
已对一种对卤代乙基亚硝基脲的细胞毒性作用敏感的神经胶质细胞系（SF - 126）提取物，以及对这些药物具有抗性的细胞系（SF - 188）提取物进行了测试，以检测它们从经[3H]硫酸二甲酯修饰的DNA底物中释放甲基化碱基的能力。与敏感细胞系相比，抗性细胞系的提取物具有高2 - 3倍的酶活性。这些提取物释放的碱基的高效液相色谱图谱表明，该活性对3 - 甲基腺嘌呤具有特异性，这表明抗性细胞中3 - 甲基腺嘌呤DNA糖基化酶的水平升高。先前的研究表明，这些细胞中O6 - 烷基鸟嘌呤 - DNA烷基转移酶的水平也升高，这表明这两种酶活性可能都参与了该细胞系对卤代乙基亚硝基脲的抗性。
