Gorbacheva L B, Vasil'eva S V, Makhova E V, Moshkovskaia E Iu, Sokolova I S, Tikhomirov A G, Dederer L Iu
N.M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, Moscow.
Antibiot Khimioter. 1999;44(4):9-12.
Cytotoxicity genetic mechanisms such as induction of SOS-repair, excision repair and interstrand coupling induced by cycloplatam or ammine (cyclopentyl amine)-S(-) malatoplatinum (II), a new antitumor drug, were for the first time studied in comparison to those of the known drug cis-diammine dichloroplatinum (II) (DDP) in a model system of Escherichia coli. In the cells of E. coli the cycloplatam cytotoxicity was much lower than that of DDP. Both the drugs induced SOS-repair in E. coli PQ37. In a concentration of 25 microM DDP was 20 times as active as cycloplatam. In concentrations of 40 to 100 microM the difference leveled. Both the drugs induced interstrand coupling in specimens of pure DNA from calf thymus and E. coli. When the cells of the wild type E. coli AB1157 were incubated in the presence of the drugs only DDP induced the DNA interstrand coupling. No correlation between the DNA interstrand coupling induced by cycloplatam or DDP and cytotoxicity of the drugs was observed.
首次在大肠杆菌模型系统中，将新型抗肿瘤药物环铂或氨（环戊胺）-S（-）苹果酸铂（II）诱导的细胞毒性遗传机制，如SOS修复诱导、切除修复和链间偶联，与已知药物顺二氨二氯铂（II）（DDP）的这些机制进行了比较研究。在大肠杆菌细胞中，环铂的细胞毒性远低于DDP。两种药物均能诱导大肠杆菌PQ37中的SOS修复。在25微摩尔浓度下，DDP的活性是环铂的20倍。在40至100微摩尔浓度下，差异趋于平缓。两种药物均能诱导小牛胸腺和大肠杆菌纯DNA样本中的链间偶联。当野生型大肠杆菌AB1157细胞在药物存在下孵育时，只有DDP能诱导DNA链间偶联。未观察到环铂或DDP诱导的DNA链间偶联与药物细胞毒性之间的相关性。
