Buchanan R L, Gralla J D
Department of Chemistry and Biochemistry, University of California, Los Angeles 90024.
Biochemistry. 1990 Apr 10;29(14):3436-42. doi: 10.1021/bi00466a003.
Isolates of SV40 that have enhanced ability to survive inhibition by the antitumor drug cisplatin were selected by serial drug challenge in vivo. These mutant viruses have acquired specific deletions within the repeated regulatory motif (GGGCGG)6 or GC box. This DNA element was shown previously to be a strong target of drug attack by cisplatin and other anticancer drugs in vitro and is an important viral and cellular DNA control sequence. Thus, drug resistance in this viral test system is dependent on the loss of important target DNA sequences. The results also indicate that drug efficacy may be related to the ability of certain anticancer drugs to attack regulatory DNA sequences containing strings of guanosines.
通过在体内进行连续药物攻击,筛选出了对抗肿瘤药物顺铂抑制具有更强存活能力的SV40分离株。这些突变病毒在重复调控基序(GGGCGG)6或GC盒内获得了特定缺失。该DNA元件先前已被证明在体外是顺铂和其他抗癌药物攻击的强大靶点,并且是重要的病毒和细胞DNA控制序列。因此,该病毒测试系统中的耐药性取决于重要靶DNA序列的缺失。结果还表明,药物疗效可能与某些抗癌药物攻击含有鸟苷串的调控DNA序列的能力有关。