Degradation of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate in human leukemic myeloblasts and lymphoblasts.

Abstract

The intracellular half-life for retention of the active triphosphate metabolite 1-beta-D-arabinofuranosylcytosine 5'-triphosphate (araCTP) of 1-beta-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 microM 1-beta-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-beta-D-arabinofuranosylcytosine metabolites. Accumulation of 1-beta-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-beta-D-arabinofuranosyluracil to 1-beta-D-arabinofuranosyluracil 5'-monophosphate was detectable in intact cells. The end product of araCTP degradation was 1-beta-D-arabinofuranosyluracil and it is proposed that conversion of 1-beta-D-arabinofuranosylcytosine 5'-monophosphate to 1-beta-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.

• Authors: G P Jamieson, L R Finch, M Snook, J S Wiley
• Journal: Cancer research (Cancer Res) Vol. 47 Issue 12 Pg. 3130-5 (Jun 15 1987) ISSN: 0008-5472 [Print] United States
• PMID: 3472653 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Arabinonucleotides
• Thionucleosides
• Cytarabine
• Guanosine
• 6-(4-nitrobenzylthio)guanosine
• Arabinofuranosylcytosine Triphosphate
• Thioinosine
• DCMP Deaminase
• 4-nitrobenzylthioinosine

Topics

• Arabinofuranosylcytosine Triphosphate (metabolism)
• Arabinonucleotides (metabolism)
• Cytarabine (therapeutic use)
• DCMP Deaminase (metabolism)
• Guanosine (analogs & derivatives, pharmacology)
• Half-Life
• Humans
• Kinetics
• Leukemia, Lymphoid (metabolism)
• Leukemia, Myeloid, Acute (metabolism)
• Lymphocytes (metabolism)
• Phosphorylation
• Thioinosine (analogs & derivatives, pharmacology)
• Thionucleosides (pharmacology)