2'-Deoxycoformycin-induced hemolysis in the mouse

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.