Degradation of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate in human leukemic myeloblasts and lymphoblasts.
The intracellular half-life for retention of the active triphosphate metabolite 1-beta-D-arabinofuranosylcytosine 5'-triphosphate (araCTP) of 1-beta-D-arabinofuranosylcytosine was measured in vitro in blast cells from patients with acute myeloblastic leukemia, acute lymphoblastic leukemia, and T-cell lymphoblastic lymphoma. araCTP accumulation from 1 microM 1-beta-D-arabinofuranosylcytosine in leukemic blast cells was closely correlated with the nucleoside transport capacity as measured by equilibrium binding of [3H]nitrobenzylthioinosine. The half-life of araCTP retention was related to araCTP accumulation only when the level of araCTP was expressed as a percentage of total intracellular 1-beta-D-arabinofuranosylcytosine metabolites. Accumulation of 1-beta-D-arabinofuranosyluracil 5'-monophosphate was inversely related to the half-life of araCTP retention and directly related to dCMP deaminase activity in cell free extracts. No conversion of 1-beta-D-arabinofuranosyluracil to 1-beta-D-arabinofuranosyluracil 5'-monophosphate was detectable in intact cells. The end product of araCTP degradation was 1-beta-D-arabinofuranosyluracil and it is proposed that conversion of 1-beta-D-arabinofuranosylcytosine 5'-monophosphate to 1-beta-D-arabinofuranosyluracil 5'-monophosphate is a step in the degradative pathway of araCTP. However, it is the cells' nucleoside transport capacity which primarily determines the level of intracellular araCTP accumulation.
Jamieson
G P
GP
Finch
L R
LR
Snook
M
M
Wiley
J S
JS
D001085:Arabinofuranosylcytosine Triphosphate / Q000378:metabolism*; D001088:Arabinonucleotides / Q000378:metabolism*; D003561:Cytarabine / Q000627:therapeutic use; D003844:DCMP Deaminase / Q000378:metabolism; D006151:Guanosine / Q000031:analogs & derivatives / Q000494:pharmacology; D006207:Half-Life; D006801:Humans; D007700:Kinetics; D007945:Leukemia, Lymphoid / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism*; D010766:Phosphorylation; D013868:Thioinosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013872:Thionucleosides / Q000494:pharmacology
D001088:Arabinonucleotides; D013872:Thionucleosides; D003561:Cytarabine; D006151:Guanosine; C002121:6-(4-nitrobenzylthio)guanosine; D001085:Arabinofuranosylcytosine Triphosphate; D013868:Thioinosine; D003844:DCMP Deaminase; C001789:4-nitrobenzylthioinosine