Bodell W J, Aida T, Berger M S, Rosenblum M L
Carcinogenesis. 1986 Jun;7(6):879-83. doi: 10.1093/carcin/7.6.879.
We investigated the cytotoxic and cytogenetic effects of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) treatment on two cell lines derived from human glioma biopsy specimens. SF-188 cells are 3-fold more resistant to the cytotoxic effects of BCNU and 14-fold more resistant to sister chromatid exchange (SCE) induction caused by BCNU treatment than are SF-126 cells. After treatment with BCNU, 60% fewer DNA interstrand crosslinks were found in SF-188 than in SF-126 cells. The O6-methylguanine alkylation product was removed rapidly from DNA in SF-188 cells treated with [3H]methylnitrosourea, but very little repair of alkylation product occurred in SF-126 cells. These results suggest that one of the mechanisms responsible for cellular resistance to BCNU treatment is increased repair of O6-alkylguanine products in DNA, which reduces the number of crosslinks formed and thereby increases survival and reduces the number of SCEs induced in resistant cells.
我们研究了1,3-双(2-氯乙基)-1-亚硝基脲(BCNU)处理对源自人胶质瘤活检标本的两种细胞系的细胞毒性和细胞遗传学效应。与SF-126细胞相比，SF-188细胞对BCNU的细胞毒性作用的抗性高3倍，对BCNU处理引起的姐妹染色单体交换(SCE)诱导的抗性高14倍。用BCNU处理后，在SF-188细胞中发现的DNA链间交联比SF-126细胞中少60%。在用[3H]甲基亚硝基脲处理的SF-188细胞中，O6-甲基鸟嘌呤烷基化产物从DNA中迅速去除，但在SF-126细胞中烷基化产物的修复很少发生。这些结果表明，细胞对BCNU处理产生抗性的机制之一是DNA中O6-烷基鸟嘌呤产物的修复增加，这减少了形成的交联数量，从而提高了存活率并减少了抗性细胞中诱导的SCE数量。
