Specific cytotoxicity of arabinosylguanine toward cultured T lymphoblasts

Buddy Ullman, D. W. Martin

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Purine nucleoside phosphorylase (PNP) deficiency in humans is associated with a severe T cell immunodeficiency. To understand further and exploit this T cell lymphospecificity, we have compared the cytotoxicities and metabolism of deoxyguanosine, the cytotoxic substrate of PNP and of arabinosylguanine, a deoxyguanosine analogue that is resistant to PNP cleavage, in T cell (8042) and B cell (8392) lines in continuous culture established from the same patient. In comparative growth rate experiments the T cells were 2.3-fold and 400-fold more sensitive to growth inhibition by deoxyguanosine and arabinosylguanine, respectively, than were the B cells. Only the T cells, but not the B cells, could phosphorylate in situ deoxyguanosine or arabinosylguanine to the corresponding triphosphate. Both the phosphorylation and cytotoxicity of arabinosylguanine in the T cell line could be prevented by deoxycytidine, which suggests that deoxycytidine-deoxyguanosine kinase initiated the intracellular metabolism and cytotoxicity of this nucleoside analogue. The sensitivity and selectivity of arabinosylguanine towards the T lymphoblastoid cells suggests a rational approach to the design of chemotherapeutic agents that are directed toward T cell malignancies and other T cell disorders.

Original languageEnglish (US)
Pages (from-to)951-955
Number of pages5
JournalJournal of Clinical Investigation
Volume74
Issue number3
StatePublished - 1984

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T-Lymphocytes
Deoxyguanosine
Purine-Nucleoside Phosphorylase
B-Lymphocytes
deoxyguanosine kinase
Deoxycytidine Kinase
Cell Line
Deoxycytidine
Growth
Nucleosides
Phosphorylation
Neoplasms

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Specific cytotoxicity of arabinosylguanine toward cultured T lymphoblasts. / Ullman, Buddy; Martin, D. W.

In: Journal of Clinical Investigation, Vol. 74, No. 3, 1984, p. 951-955.

Research output: Contribution to journalArticle

Ullman, Buddy ; Martin, D. W. / Specific cytotoxicity of arabinosylguanine toward cultured T lymphoblasts. In: Journal of Clinical Investigation. 1984 ; Vol. 74, No. 3. pp. 951-955.
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