Ducore J M, Rosenstein B S
Mutat Res. 1985 Jul;146(1):1-8. doi: 10.1016/0167-8817(85)90048-3.
This report demonstrates the synergistic killing of murine L1210 leukemia in vitro by BCNU and theophylline as has previously been reported in vivo. Synergism is also seen with the related nitrosourea CNU plus theophylline. As measured on alkaline sucrose gradients and by pH-step alkaline elution, the nitrosourea-induced inhibition of DNA replicon initiation is completely reversed in the presence of theophylline. DNA interstrand crosslinking, the damage which usually correlates with nitrosourea cytotoxicity, is not increased by the combination of nitrosourea plus theophylline. At high nitrosourea doses, this interstrand crosslinking is reduced in the presence of theophylline. At least part of the mechanism of the two-drug synergism is the theophylline release of nitrosourea-induced DNA initiation inhibition. Some of the results have been presented at the Annual Meeting of the American Association for Cancer Research.
本报告证明，如先前在体内所报道的那样，卡莫司汀（BCNU）与茶碱在体外对小鼠L1210白血病具有协同杀伤作用。亚硝基脲类药物洛莫司汀（CNU）与茶碱联用也可见协同作用。通过碱性蔗糖梯度法和pH梯度碱性洗脱法测定，在茶碱存在的情况下，亚硝基脲类药物对DNA复制子起始的抑制作用完全逆转。DNA链间交联是通常与亚硝基脲类药物细胞毒性相关的损伤，亚硝基脲类药物与茶碱联用不会使其增加。在高剂量亚硝基脲类药物情况下，茶碱存在时链间交联会减少。两药协同作用的机制至少部分是由于茶碱解除了亚硝基脲类药物诱导的DNA起始抑制。部分研究结果已在美国癌症研究协会年会上发表。
