顺二氯二氨铂（II）与阿糖胞苷对DNA化学相互作用水平及小鼠白血病生长的协同作用评估。

Evaluation of synergism of drugs cis-diamminedichloroplatinum (II) and arabinosylcytosine on the level of chemical interaction with DNA and on the growth of mouse leukemia.

Rauko P, Novotný L, Reichelová V, Balázová E

Cancer Research Institute, Slovak Academy of Sciences, Bratislava, Czechoslovakia.

Gen Pharmacol. 1991;22(5):805-10. doi: 10.1016/0306-3623(91)90210-w.

Abstract

Cytotoxic synergism of drugs cis-diamminedichloroplatinum(II) (cis-DDP) and arabinosylcytosine (araC) was studied both on the level of interaction with DNA in chemically determined conditions and on leukemia L1210 bearing mice. 2. AraC and its structural natural precursor cytidine were tested for the modulation of kinetics of bifunctional adducts production induced by cis-DDP in DNA. 3. This process plays the basic role in cytotoxic mechanism and antitumor activity of cis-DDP. 4. No interaction was seen between cis-DDP and araC. Further, presence of araC in reaction mixture had no effect on cis-DDP-DNA interaction. 5. Therefore, cytotoxic synergism does not arise in the araC-cis-DDP-DNA interaction and its origin is different. 6. Finding that cytidine has no synergistic effect on life span of leukemia L1210 bearing mice when administered together with cis-DDP it shows the difference between cytidine and araC. 7. The small structural difference between cytidine and araC is very important for synergism of cytotoxicity.

摘要

研究了顺二氯二氨铂（II）（顺铂）和顺式阿糖胞苷（阿糖胞苷）在化学确定条件下与DNA相互作用水平以及对携带白血病L1210小鼠的细胞毒性协同作用。2. 测试了阿糖胞苷及其结构天然前体胞苷对顺铂诱导的DNA中双功能加合物产生动力学的调节作用。3. 该过程在顺铂的细胞毒性机制和抗肿瘤活性中起基本作用。4. 顺铂和阿糖胞苷之间未观察到相互作用。此外，反应混合物中阿糖胞苷的存在对顺铂 - DNA相互作用没有影响。5. 因此，阿糖胞苷 - 顺铂 - DNA相互作用中不会产生细胞毒性协同作用，其起源不同。6. 发现胞苷与顺铂一起给药时对携带白血病L1210小鼠的寿命没有协同作用，这表明了胞苷和阿糖胞苷之间的差异。7. 胞苷和阿糖胞苷之间微小的结构差异对细胞毒性协同作用非常重要。