Saturation of intracellular cytosine arabinoside triphosphate accumulation in human leukemic blast cells.
Accumulation of cytosine arabinoside triphosphate (araCTP) from a range of cytosine arabinoside (araC) concentrations (1-50 microM) was measured during incubations of leukemic cells freshly isolated from patients with acute leukemia. In all but one patient, increments in extracellular araC above 10 microM did not increase intracellular araCTP levels. This maximal level of araCTP accumulation ranged from 254 to 1607 pmol/10(7) cells attained after 1 h incubation and did not correlate with either the number of nucleoside transporters on the cell membrane or the Vmax of araC phosphorylation in cell free extracts. Extremely low araCTP accumulation (103 pmol/10(7) cells/h at 50 microM araC) was observed in an AML patient with the unusual finding of micromyeloblasts. These cells also had very low numbers of nucleoside transport sites (less than 500 sites/cell) and were mitotically inactive. The unique feature of the myeloblasts from this patient was that intracellular araCTP accumulation showed a linear dependence on extracellular araC up to 50 microM with no evidence of saturation.
Jamieson
G P
GP
Department of Haematology, Austin Hospital, Heidelberg, Melbourne, Australia.
Snook
M B
MB
Wiley
J S
JS
D000208:Acute Disease; D001085:Arabinofuranosylcytosine Triphosphate / Q000493:pharmacokinetics*; D001088:Arabinonucleotides / Q000493:pharmacokinetics*; D001665:Binding Sites; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D003561:Cytarabine / Q000008:administration & dosage / Q000378:metabolism; D003842:Deoxycytidine Kinase / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000201:enzymology / Q000378:metabolism*; D008214:Lymphocytes / Q000378:metabolism; D009705:Nucleosides / Q000378:metabolism; D010766:Phosphorylation; D013868:Thioinosine / Q000031:analogs & derivatives / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000201:enzymology / Q000378:metabolism
D001088:Arabinonucleotides; D009705:Nucleosides; D003561:Cytarabine; D001085:Arabinofuranosylcytosine Triphosphate; D013868:Thioinosine; D003842:Deoxycytidine Kinase; C001789:4-nitrobenzylthioinosine