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抗肿瘤咪唑并四嗪类化合物二十八:对替莫唑胺敏感和耐药细胞系中的3-甲基腺嘌呤DNA糖基化酶活性

Antitumour imidazotetrazines XXVIII 3-methyladenine DNA glycosylase activity in cell lines sensitive and resistant to temozolomide.

作者信息

Deans B, Tisdale M J

机构信息

Pharmaceutical Sciences Institute, Aston University, Birmingham, UK.

出版信息

Cancer Lett. 1992 Apr 15;63(2):151-7. doi: 10.1016/0304-3835(92)90065-4.

DOI:10.1016/0304-3835(92)90065-4
PMID:1562991
Abstract

The ability of extracts of a range of cell lines to release methylated bases from a DNA substrate, which had been modified with [3H]dimethyl sulphate, has been compared in cell lines with differing sensitivity to the cytotoxic drug, temozolomide. High performance liquid chromatography profiles of the bases released by these extracts showed that the activity was specific for 3-methyladenine. There was little variation in the level of 3-methyladenine-DNA glycosylase between the different cell lines despite a 40-fold difference in sensitivity to temozolomide and no correlation with the level of O6-alkylguanine-DNA alkyltransferase.

摘要

已对一系列细胞系的提取物从经[3H]硫酸二甲酯修饰的DNA底物中释放甲基化碱基的能力进行了比较,这些细胞系对细胞毒性药物替莫唑胺的敏感性不同。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。尽管对替莫唑胺的敏感性相差40倍,但不同细胞系之间3-甲基腺嘌呤-DNA糖基化酶的水平几乎没有差异,且与O6-烷基鸟嘌呤-DNA烷基转移酶的水平无关。

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Design and mechanism of action of a novel cytotoxic 1,2,3-triazene-containing heterocycle, 3,5-dimethyl-pyrido-1,2,3,5-tetrazepin-4-one (PYRZ), in the human epithelial ovarian cancer cell line NIH:OVCAR-3 in vitro.新型含1,2,3 - 三氮烯杂环化合物3,5 - 二甲基 - 吡啶并 - 1,2,3,5 - 四氮杂卓 - 4 - 酮(PYRZ)在人上皮性卵巢癌细胞系NIH:OVCAR - 3中的体外设计及作用机制
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