Biochemical Basis for the Enhanced Toxicity of Deoxyribonucleosides toward Malignant Human T Cell Lines

Human malignant T cell lines have high levels of deoxyribonucleoside phosphorylating activity and low levels of deoxyribonucleotide dephosphorylating activity. When incubated with deoxyadenosine or thymidine, the malignant T cell lines rapidly accumulate toxic concentrations of dATP and dTTP, respec...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1979-05, Vol.76 (5), p.2430-2433
Main Authors: Carson, Dennis A., Kaye, Jonathan, Matsumoto, Steven, Seegmiller, J. E., Thompson, Linda
Format: Article
Language:English
Subjects:
B lymphocytes
B-Lymphocytes - metabolism
Biochemistry
Cell Line
Cell lines
Deoxyadenine Nucleotides - metabolism
Deoxyadenosines - metabolism
Deoxyribonucleosides
Deoxyribonucleosides - toxicity
Deoxyribonucleotides
Deoxyribonucleotides - metabolism
DNA
Enzymes
Humans
Nucleosides
Nucleotidases - metabolism
Nucleotides
T lymphocytes
T-Lymphocytes - drug effects
T-Lymphocytes - metabolism
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Summary:Human malignant T cell lines have high levels of deoxyribonucleoside phosphorylating activity and low levels of deoxyribonucleotide dephosphorylating activity. When incubated with deoxyadenosine or thymidine, the malignant T cell lines rapidly accumulate toxic concentrations of dATP and dTTP, respectively. This unusual pattern of deoxyribonucleotide metabolism renders the malignant T cells especially vulnerable to the toxic effects of deoxyribonucleosides and related analogues.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.76.5.2430