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

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  • Cytosine Arabinoside
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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.

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Author notes

  1. Adrian L. Harris

    Present address: Department of Medicine, Royal Marsden Hospital, Fulham Road, SW3, London, Great Britain

Authors and Affiliations

  1. MRC Clinical Pharmacology Department, Radcliffe Infirmary, Woodstock Road, Oxford, Great Britain

    Adrian L. Harris & David G. Grahame-Smith

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  1. Adrian L. Harris
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  2. David G. Grahame-Smith
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Harris, A.L., Grahame-Smith, D.G. Cytosine arabinoside triphosphate production in human leukaemic myeloblasts: Interactions with deoxycytidine. Cancer Chemother. Pharmacol. 5, 185–192 (1981). https://doi.org/10.1007/BF00258478

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  • DOI: https://doi.org/10.1007/BF00258478

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