Spremulli E, Crabtree G W, Dexter D L, Diamond I, Calabresi P
J Natl Cancer Inst. 1982 Jun;68(6):1011-4.
2'-Deoxycoformycin (dCF), a tight-binding inhibitor of adenosine deaminase, has recently been entered into clinical trials. Toxicity has included lymphopenia, seizures, coma, conjunctivitis, renal failure, and hemolysis. Mice treated with dCF on a variety of schedules exhibited massive hemolysis. Hemolysis was brief, lasting about 20 hours, and did not recur upon readministration of the drug unless readministration was delayed for at least 6 days after initial exposure, which suggests that a sensitive subpopulation of cells was selectively destroyed. Splenectomy failed to protect the animals from dCF-induced hemolysis. Administration of adenosine or 2'-deoxyadenosine without dCF did not cause hemolysis, and use of these two agents with dCF did not potentiate the observed hemolysis. ATP and dATP levels were measured in erythrocytes, and changes in levels of these nucleotides did not correspond with the development of hemolysis.
2'-脱氧助间型霉素(dCF)是一种腺苷脱氨酶的紧密结合抑制剂,最近已进入临床试验阶段。其毒性包括淋巴细胞减少、癫痫发作、昏迷、结膜炎、肾衰竭和溶血。以各种给药方案用dCF处理的小鼠出现了大量溶血现象。溶血过程短暂,持续约20小时,再次给药时除非在初次接触后至少延迟6天给药,否则溶血不会复发,这表明有一个敏感的细胞亚群被选择性破坏。脾切除未能保护动物免受dCF诱导的溶血。单独给予腺苷或2'-脱氧腺苷不会引起溶血,同时使用这两种药物与dCF也不会增强所观察到的溶血现象。测定了红细胞中的ATP和dATP水平,这些核苷酸水平的变化与溶血的发生并不对应。