Cytosine arabinoside triphosphate production in human leukaemic myeloblasts: interactions with deoxycytidine.
The effect of 1 mu M deoxycytidine (dC) on Ara-C conversion to Ara-CTP and on inhibition of DNA synthesis by Ara-C was measured in intact leukaemic myeloblasts. dC decreased Ara-CTP production in blasts with high Ara-C phosphorylation, but not those with low activity. The Ki for dC was similar to values found with partially purified deoxycytidine kinase. The change in Ara-CTP concentration was associated with a proportional reduction in inhibition of DNA synthesis. dC decreased the effects of Ara-C by inhibition of Ara-CTP production, rather than by production of dCTP and competition with Ara-CTP. Since low Ara-CTP production in patients' blasts is a predictor of poor therapeutic response to Ara-C, the use of dC with Ara-C may improve the therapeutic index in this group of patients.
D001085:Arabinofuranosylcytosine Triphosphate / Q000378:metabolism*; D001088:Arabinonucleotides / Q000378:metabolism*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D003841:Deoxycytidine / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D015470:Leukemia, Myeloid, Acute / Q000378:metabolism*; D010766:Phosphorylation; D013767:Tetrahydrouridine / Q000494:pharmacology
D001088:Arabinonucleotides; D004273:DNA, Neoplasm; D003841:Deoxycytidine; D001085:Arabinofuranosylcytosine Triphosphate; D013767:Tetrahydrouridine