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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.

Type

Journal article

Journal

Cancer Chemother Pharmacol

Publication Date

1981

Volume

5

Pages

185 - 192

Keywords

Arabinofuranosylcytosine Triphosphate, Arabinonucleotides, DNA, Neoplasm, Deoxycytidine, Humans, Kinetics, Leukemia, Myeloid, Acute, Phosphorylation, Tetrahydrouridine