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Degradation of 1-ß-D-Arabinofuranosylcytosine 5'-Triphosphate in Human Leukemic Myeloblasts and Lymphoblasts¹

Department of Haematology [G. P. J., M. S., J. S. W.], Austin Hospital, Heidelberg, Melbourne, 3084, and Russell Grimwade School of Biochemistry [L. R. F.], University of Melbourne, Parkville, Melbourne, 3052, Australia

The intracellular half-life for retention of the active triphosphate metabolite 1-ß-D-arabinofuransylcytosine 5'-triphosphate (araCTP) of 1-ß-D-arabinofuranosylcytosine was measured in vitro in blast cells from patients with acute myeloblastic leukemia, acute lymphoblastic leukemia, and T-cell lymphoblastic lymphoma. araCTP accumulation from 1 µM 1-ß-D-arabinofuranosylcytosine in leukemic blast cells was closely correlated with the nucleoside transport capacity as measured by equilibrium binding of [³H]nitrobenzylthioinosine. The half-life of araCTP retention was related to araCTP accumulation only when the level of araCTP was expressed as a percentage of total intracellular 1-ß-D-arabinofuranosylcytosine metabolites. Accumulation of 1-ß-D-arabinofuranosyluracil 5'-monophosphate was inversely related to the half-life of araCTP retention and directly related to dCMP deaminase activity in cell free extracts. No conversion of 1-ß-D-arabinofuranosyluracil to 1-ß-D-arabinofuranosyluracil 5'-monophosphate was detectable in intact cells. The end product of araCTP degradation was 1-ß-D-arabinofuranosyluracil and it is proposed that conversion of 1-ß-D-arabinofuranosylcytosine 5'-monophosphate to 1-ß-D-arabinofuranosyluracil 5'-monophosphate is a step in the degradative pathway of araCTP. However, it is the cells' nucleoside transport capacity which primarily determines the level of intracellular araCTP accumulation.

¹ This research was carried out during the tenure of a grant from the Anti Cancer Council of Victoria.

² To whom requests for reprints should be addressed.

Received 11/25/85. Revised 2/ 4/87. Accepted 3/13/87.

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