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 language | English (US) |
|---|---|
| Pages (from-to) | 951-955 |
| Number of pages | 5 |
| Journal | Journal of Clinical Investigation |
| Volume | 74 |
| Issue number | 3 |
| State | Published - 1984 |
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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 journal › Article
}
TY - JOUR
T1 - Specific cytotoxicity of arabinosylguanine toward cultured T lymphoblasts
AU - Ullman, Buddy
AU - Martin, D. W.
PY - 1984
Y1 - 1984
N2 - 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.
AB - 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.
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M3 - Article
C2 - 6332120
AN - SCOPUS:0021159928
VL - 74
SP - 951
EP - 955
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 3
ER -