Potential use of purine nucleosides and enzyme inhibitors for selective depletion of Thy-lymphoblasts from human bone marrow.
The toxicity of the purine nucleoside, deoxyadenosine in the presence of the adenosine deaminase inhibitor, deoxycoformycin and of deoxyguanosine in the presence of the purine nucleoside phosphorylase inhibitor, 8-aminoguanosine was measured against two Thy-leukemic cell lines. Toxicity was assessed by the survival of clonogenic cells in a colony assay. The kill of clonogenic Thy-leukemic cells was 99.99% with both nucleoside enzyme inhibitor combinations following 4-h incubations when 50 microM concentration of nucleoside were used. With these nucleoside concentrations some reduction in toxicity was apparent when drug treated cells were cultured in the presence of deoxycytidine (50 microM), however, this reduction in toxicity was not apparent when higher nucleoside concentrations were used (100 microM). Survival of bone marrow myeloid progenitor cells (CFU.GM) was only slightly reduced by these nucleoside concentrations following 4 hour incubations. The presence of a twenty-fold excess of normal bone marrow cells reduced the cytotoxic effect but clonogenic cell incubation still ranged from 99.98 to 99.99% for deoxyguanosine and deoxyadenosine respectively. These combinations of nucleosides and enzyme inhibitors may have a therapeutic role in the elimination of malignant Thy cells from human bone marrow.
Russell
N H
NH
Hoffbrand
A V
AV
Bellingham
A J
AJ
D058892:Adenosine Deaminase Inhibitors; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D001853:Bone Marrow / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003070:Coformycin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D003839:Deoxyadenosines / Q000008:administration & dosage / Q000494:pharmacology*; D003841:Deoxycytidine / Q000494:pharmacology; D003849:Deoxyguanosine / Q000008:administration & dosage / Q000494:pharmacology*; D006151:Guanosine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects; D006801:Humans; D007945:Leukemia, Lymphoid / Q000188:drug therapy* / Q000473:pathology; D009700:Nucleoside Deaminases / Q000037:antagonists & inhibitors*; D015649:Pentostatin; D010430:Pentosyltransferases / Q000037:antagonists & inhibitors*; D011683:Purine-Nucleoside Phosphorylase / Q000037:antagonists & inhibitors*; D012263:Ribonucleosides / Q000494:pharmacology*; D014410:Tumor Stem Cell Assay
D058892:Adenosine Deaminase Inhibitors; D003839:Deoxyadenosines; D012263:Ribonucleosides; D003841:Deoxycytidine; D003070:Coformycin; D006151:Guanosine; C032533:8-aminoguanosine; D015649:Pentostatin; D010430:Pentosyltransferases; D011683:Purine-Nucleoside Phosphorylase; D009700:Nucleoside Deaminases; D003849:Deoxyguanosine