Cancer Chemotherapy and Pharmacology

, Volume 5, Issue 3, pp 185–192 | Cite as

Cytosine arabinoside triphosphate production in human leukaemic myeloblasts: Interactions with deoxycytidine

  • Adrian L. Harris
  • David G. Grahame-Smith
Original Articles Cytosine Arabinoside
Received:
Accepted:

Summary

The effect of 1 μM 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.

Keywords

Cancer Research Cytosine Triphosphate Therapeutic Response Deoxycytidine 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Copyright information

© Springer-Verlag 1981

Authors and Affiliations

  • Adrian L. Harris
    • 1
  • David G. Grahame-Smith
    • 1
  1. 1.MRC Clinical Pharmacology DepartmentRadcliffe InfirmaryOxfordGreat Britain

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