Mong S, Huang C H, Prestayko A W, Crooke S T
Cancer Res. 1980 Sep;40(9):3313-7.
The interaction of cis-diamminedichloroplatinum(II) (CDDP) with PM-2 DNA was studied using two techniques: (a) agarose gel electrophoresis of PM-2 DNA conformation isomers after CDDP binding; and (b) viscometric measurement of different forms of CDDP-bound PM-2 DNA. In both systems, the results indicated that the DNA isomers interacted differently with CDDP. CDDP induced a decrease of viscosity upon interacting with single-strand broken relaxed circular (Form II) and double-strand broken linear (Form III) PM-2 DNA's. These observations are consistent with a "DNA shortening effect" proposed by Cohen et al. [Science (Wash. D. C.), 203: 1014-1016, 1979] and Macquet et al. [Biochimie (Paris), 60: 901-914, 1978] When covalently closed circular (Form I) PM-2 DNA was used, increasing concentrations of CDDP induced an initial slight increase and then decrease of electrophoretic mobility to the degree that it comigrated with CDDP-bound Form II DNA. Further addition of CDDP restored the electrophoretic mobility of Form I DNA. Corresponding changes in the viscosity of CDDP-bound Form I DNA showed an initial decrease, then an increase, and a final prolonged decrease of viscosity. These effects are similar but not identical to those induced by either DNA intercalators (e.g., ethidium bromide) or certain DNA denaturating agents (e.g., formaldehyde, ultraviolet light, alkali trichloroacetate, methylmercuric hydroxide, and carbodiimide). Thus, CDP may induce a DNA superhelix-unwinding process followed either by rewinding or a denaturation process or both. Quantitative analysis of the agarose gel electrophoretic pattern plus sucrose density gradient centrifugation studies also indicated that there was little DNA strand breakage induced by CDDP treatment.
采用两种技术研究了顺二氯二氨合铂（II）（CDDP）与PM - 2 DNA的相互作用：（a）CDDP结合后PM - 2 DNA构象异构体的琼脂糖凝胶电泳；（b）不同形式的CDDP结合的PM - 2 DNA的粘度测量。在这两个系统中，结果表明DNA异构体与CDDP的相互作用不同。CDDP与单链断裂的松弛环状（形式II）和双链断裂的线性（形式III）PM - 2 DNA相互作用时会导致粘度降低。这些观察结果与Cohen等人[《科学》（华盛顿特区），203: 1014 - 1016，1979]和Macquet等人[《生物化学》（巴黎），60: 901 - 914，1978]提出的“DNA缩短效应”一致。当使用共价闭合环状（形式I）PM - 2 DNA时，CDDP浓度增加会导致电泳迁移率最初略有增加，然后降低，直至与CDDP结合的形式II DNA共迁移。进一步添加CDDP可恢复形式I DNA的电泳迁移率。CDDP结合的形式I DNA粘度的相应变化显示出最初降低，然后增加，最后粘度长时间降低。这些效应与DNA嵌入剂（如溴化乙锭）或某些DNA变性剂（如甲醛、紫外线、碱式三氯乙酸、甲基汞氢氧化物和碳二亚胺）诱导的效应相似但不完全相同。因此，CDP可能诱导DNA超螺旋解旋过程，随后是重新缠绕或变性过程或两者兼有。琼脂糖凝胶电泳图谱的定量分析以及蔗糖密度梯度离心研究还表明，CDDP处理诱导的DNA链断裂很少。
