DeNeve W J, Everett C K, Suminski J E, Valeriote F A
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48201.
Cancer Res. 1988 Nov 1;48(21):6002-5.
In previous studies we showed that WR2721 enhanced nitrogen mustard (HN2) cytotoxicity to AKR mouse leukemia. Simultaneously, it protected normal bone marrow from drug cytotoxicity. In this study, the method of alkaline elution was used to measure the modifications of HN2 induced DNA damage in the same animal model. In leukemia cells, no significant differences in DNA-DNA interstrand cross-links were observed between mice treated with WR2721 and HN2 and mice treated with HN2 alone. In normal bone marrow, DNA-DNA cross-linking was decreased by about 50% in mice treated by WR2721 and HN2. The difference was significant (P = 0.01). In leukemia, half-time of repair was 73 min for HN2 and 83 for WR2721 and HN2 treated mice, while in normal bone marrow, respectively, 73 and 64 min were calculated. WR2721 modulation significantly decreases DNA-protein cross-links in leukemia cells (P less than 0.05). This decrease was observed for early as well as for late DNA-protein cross-links. In normal bone marrow cells, only early DNA-protein cross-links were decreased. The meaning of this observation is unclear.
在之前的研究中，我们表明WR2721可增强氮芥（HN2）对AKR小鼠白血病的细胞毒性。同时，它能保护正常骨髓免受药物细胞毒性的影响。在本研究中，采用碱性洗脱法在同一动物模型中测量HN2诱导的DNA损伤的变化。在白血病细胞中，用WR2721和HN2处理的小鼠与仅用HN2处理的小鼠之间，在DNA - DNA链间交联方面未观察到显著差异。在正常骨髓中，用WR2721和HN2处理的小鼠的DNA - DNA交联减少了约50%。差异具有显著性（P = 0.01）。在白血病中，HN2处理的小鼠修复半衰期为73分钟，WR2721和HN2处理的小鼠为83分钟，而在正常骨髓中，分别计算为73分钟和64分钟。WR2721调节可显著降低白血病细胞中的DNA - 蛋白质交联（P小于0.05）。早期和晚期的DNA - 蛋白质交联均观察到这种降低。在正常骨髓细胞中，仅早期DNA - 蛋白质交联减少。这一观察结果的意义尚不清楚。
