DeNeve W, Valeriote F, Tapazoglou E, Everett C, Khatana A, Corbett T
Wayne State University School of Medicine, Department of Internal Medicine, Detroit, MI 48201.
Invest New Drugs. 1990 Feb;8(1):17-24. doi: 10.1007/BF00216920.
We used the method of alkaline elution to compare quantitatively the DNA lesions produced by cisplatin and carboplatin in the AKR leukemia in vivo. These data were compared with cytotoxicity of each drug in the same animal model and in a solid tumor murine model (colon 26). DNA-protein and DNA-DNA interstrand crosslinks were formed in similar proportions by both drugs when peak values of crosslinking were compared. No clear difference in the rate of formation of both types of crosslinks could be observed between these drugs. On a molar basis a 3- to 4-fold more carboplatin had to be given to obtain equivalent frequencies of both types of crosslinks. In contrast, to obtain equitoxicity in the same animal tumor model, 13 fold higher doses of carboplatin had to be given. This difference in cytotoxicity between both drugs is comparable to the difference measured in colon 26 in vivo (16 fold). Both values are in the range of literature data (10-25 fold) dealing with the relative potency of cisplatin and carboplatin in murine tumor models.
我们采用碱性洗脱法对顺铂和卡铂在体内AKR白血病中产生的DNA损伤进行定量比较。将这些数据与每种药物在相同动物模型和实体瘤小鼠模型（结肠26）中的细胞毒性进行比较。当比较交联峰值时，两种药物形成的DNA-蛋白质和DNA-DNA链间交联比例相似。在这两种药物之间，未观察到两种类型交联形成速率的明显差异。以摩尔为基础，必须给予3至4倍剂量的卡铂才能获得同等频率的两种类型交联。相比之下，为了在相同动物肿瘤模型中获得同等毒性，必须给予高13倍剂量的卡铂。这两种药物在细胞毒性上的差异与在体内结肠26中测得的差异相当（16倍）。这两个值都在文献数据（10 - 25倍）范围内，该文献数据涉及顺铂和卡铂在小鼠肿瘤模型中的相对效力。
