Micetich K C, Barnes D, Erickson L C
Cancer Res. 1985 Sep;45(9):4043-7.
Utilizing the DNA alkaline elution technique we have compared qualitatively and quantitatively the DNA lesions produced in L1210 cells after a 2 h exposure to the antitumor agents, cis-(diammino) (1,1-cyclobutanedicarboxylato)-platinum(II) (CBDCA) and cis-diamminedichloroplatinum(II) (DDP). DNA-protein and DNA interstrand cross-links are formed in cells exposed to either CBDCA or DDP. However, in comparison to DDP peak levels of these lesions occur 6 to 12 h later in CBDCA treated cells. Cytotoxicity studies reveal that CBDCA is 45 times less potent than DDP to L1210 cells when compared on a molar basis. The decreased cytotoxicity of CBDCA and the 12 h delay in peak cross-linking when compared to DDP is interpreted as a decreased reactivity of the intact CBDCA towards the DNA. This decreased reactivity may be due in part to the presence of a stable bidentate dicarboxylate chelate ring structure of CBDCA resulting in a much slower rate of hydrolysis to the active form of the drug.
利用DNA碱性洗脱技术，我们定性和定量地比较了L1210细胞在接触抗肿瘤药物顺式（二氨基）（1,1 - 环丁烷二羧酸根）铂（II）（CBDCA）和顺式二氯二氨铂（II）（DDP）2小时后产生的DNA损伤。在接触CBDCA或DDP的细胞中会形成DNA - 蛋白质和DNA链间交联。然而，与DDP相比，这些损伤的峰值水平在CBDCA处理的细胞中6至12小时后出现。细胞毒性研究表明，按摩尔比计算时，CBDCA对L1210细胞的效力比DDP低45倍。与DDP相比，CBDCA细胞毒性的降低以及交联峰值延迟12小时被解释为完整的CBDCA对DNA的反应性降低。这种反应性降低可能部分归因于CBDCA存在稳定的双齿二羧酸螯合环结构，导致其水解为药物活性形式的速率要慢得多。
