Brabec V, Kleinwächter V, Butour J L, Johnson N P
Institute of Biophysics, Czechoslovak Academy of Sciences, Brno.
Biophys Chem. 1990 Apr;35(2-3):129-41. doi: 10.1016/0301-4622(90)80003-p.
Cisplatin (cis-diamminedichloroplatinum(II] is widely used in the treatment of various human tumours. A large body of experimental evidence indicates that the reaction of cisplatin with DNA is responsible for the cytostatic action of this drug. Several platinum-DNA adducts have been identified and their effect on the conformation of DNA has been investigated. Structural studies of platinum-DNA adducts now permit a reasonably good explanation of the biophysical properties of platinated DNA. Antitumouractive platinum compounds induce in DNA, at low levels of binding, local conformational alterations which have the character of non-denaturing distortions. It is likely that these changes occur in DNA due to the formation of intrastrand cross-links between two adjacent purine residues. On the other hand, the modification of DNA by antitumour-inactive complexes results in the formation of more severe local denaturation changes. Conformational alterations induced in DNA by antitumour-active platinum compounds may be reparable with greater difficulty than those induced by the inactive complexes. Alternatively, non-denaturation change induced in DNA by antitumour platinum drugs could represent more significant steric hindrance against DNA replication as compared with inactive complexes.
顺铂（顺 - 二氨二氯铂（II））被广泛用于治疗各种人类肿瘤。大量实验证据表明，顺铂与DNA的反应是该药物细胞抑制作用的原因。已鉴定出几种铂 - DNA加合物，并研究了它们对DNA构象的影响。铂 - DNA加合物的结构研究现在能够对铂化DNA的生物物理性质作出相当好的解释。具有抗肿瘤活性的铂化合物在低结合水平下会在DNA中诱导局部构象改变，这些改变具有非变性扭曲的特征。这些变化可能是由于两个相邻嘌呤残基之间形成链内交联而在DNA中发生的。另一方面，无抗肿瘤活性的复合物对DNA的修饰会导致更严重的局部变性变化。具有抗肿瘤活性的铂化合物在DNA中诱导的构象改变可能比无活性复合物诱导的构象改变更难修复。或者，与无活性复合物相比，抗肿瘤铂药物在DNA中诱导的非变性变化可能对DNA复制构成更显著的空间位阻。
