Effect of 2'-deoxycoformycin on erythroid, granulocytic, and T-lymphocyte colony growth.
The finding of elevated intracellular levels of adenosine deaminase (ADA) in some patients with acute lymphoblastic leukemia has led to attempts to control this disease with the adenosine deaminase inhibitor 2'-deoxycoformycin (dCF). Because of clinical reports indicating its relative freedom from myelotoxicity, we have tested the effects of this drug on erythroid, granulocytic, and T-lymphocyte colony formation by normal marrow and peripheral blood cells. While clinically the drug has been found to be active at serum concentrations of approximately 10 microM, we have tested it at concentrations up to and including 1 mM. It was found that both erythroid and granulocytic colony growth was completely unaffected by 1 mM dCF, a concentration at least 2 magnitudes higher than that necessary to totally ablate intracellular ADA levels. T-lymphocyte colony growth was unaffected by 100 microM dCF, but at 1 mM some inhibition was observed. These findings therefore indicate that dCF, while able to cause leukemic cell lysis in vivo, has no inhibitory effect on the proliferative capacity of normal hematopoietic cells.
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D058892:Adenosine Deaminase Inhibitors; D003070:Coformycin / Q000031:analogs & derivatives / Q000494:pharmacology*; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000166:cytology; D006098:Granulocytes / Q000166:cytology; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D015649:Pentostatin; D010835:Phytohemagglutinins / Q000494:pharmacology; D012263:Ribonucleosides / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000166:cytology
D058892:Adenosine Deaminase Inhibitors; D006131:Growth Inhibitors; D010835:Phytohemagglutinins; D012263:Ribonucleosides; D003070:Coformycin; D015649:Pentostatin; C010192:9-(2-hydroxy-3-nonyl)adenine; D000225:Adenine