DEOXYRIBONUCLEOSIDE TRIPHOSPHATE ACCUMULATION BY LEUKEMIC-CELLS
- 1 January 1983
- journal article
- research article
- Vol. 62 (2) , 419-424
Abstract
Toxicity of the deoxyribonucleosides, 2''-deoxyadenosine, 2''-deoxyguanosine and thymidine, for human T lymphoblasts is mediated by the accumulation of the corresponding deoxyribonucleoside triphosphate (dATP, dGTP or dTTP, respectively). It was examined whether leukemic cells of non-T-cell origin are capable of accumulating deoxyribonucleotides in culture and whether this capability correlates with the activities of purine metabolizing enzymes in these cells. Non-T, non-B acute lymphoblastic leukemia cells with low ecto-5''-nucleotidase and high adenosine deaminase activities increased their dATP pools by greater than 10-fold when exposed to deoxyadenosine and an inhibitor of adenosine deaminase in culture. Cells from 2 of 9 patients with chronic lymphocytic leukemia and 4 of 11 patients with acute nonlymphoblastic leukemia achieved similar elevations in dATP but there was no relationship between dATP accumulation and adenosine deaminase, purine nucleoside phosphorylase or ecto-5''-nucleotidase activities. Treatment of 4 individuals with acute lymphoblastic leukemia with the adenosine deaminase inhibitor, 2''-deoxycoformycin, resulted in elevations in plasma deoxyadenosine concentrations and in increments in lymphoblast dATP levels that were similar to those measured in lymphoblasts cultured with deoxyadenosine and deoxycoformycin prior to treatment. In-vitro incubations of leukemic cells with deoxyribonucleosides may provide a rational basis for the use of these compounds as chemotherapeutic agents.This publication has 24 references indexed in Scilit:
- REMISSION INDUCTION WITH ADENOSINE-DEAMINASE INHIBITOR 2'-DEOXYCOFORMYCIN IN THY-LYMPHOBLASTIC LEUKÆMIAThe Lancet, 1980
- Biochemical basis for differential deoxyadenosine toxicity to T and B lymphoblasts: role for 5'-nucleotidase.Proceedings of the National Academy of Sciences, 1979
- Biochemical basis for the enhanced toxicity of deoxyribonucleosides toward malignant human T cell lines.Proceedings of the National Academy of Sciences, 1979
- Selective toxicity of purine deoxynucleosides for human lymphocyte growth and functionProceedings of the National Academy of Sciences, 1979
- Apparent suicide inactivation of human lymphoblast S-adenosylhomocysteine hydrolase by 2'-deoxyadenosine and adenine arabinoside. A basis for direct toxic effects of analogs of adenosine.Journal of Biological Chemistry, 1979
- Differential Sensitivity of Human Leukemic T Cell Lines and B Cell Lines to Growth Inhibition by DeoxyadenosineThe Journal of Immunology, 1978
- Purinogenic immunodeficiency diseases: selective toxicity of deoxyribonucleosides for T cells.Proceedings of the National Academy of Sciences, 1978
- Deoxyguanosine Triphosphate as a Possible Toxic Metabolite in the Immunodeficiency Associated with Purine Nucleoside Phosphorylase DeficiencyJournal of Clinical Investigation, 1978
- Identification and quantitation of adenine deoxynucleotides in erythrocytes of a patient with adenosine deaminase deficiency and severe combined immunodeficiency.Journal of Biological Chemistry, 1978
- PARTIAL DEFICIENCY OF PURINE NUCLEOSIDE PHOSPHORYLASE - STUDIES OF PURINE AND PYRIMIDINE METABOLISM1978