Deoxyguanosine toxicity on lymphoid cells as a cause for immunosuppression in purine nucleoside phosphorylase deficiency

Teh sheng Chan

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

To delineate the pathogenesis of the immunodeficiency disease associated with purine nucleoside phosphorylase deficiency, the effects of guanosine, inosine, deoxyguanosine and deoxyinosine on the growth of a mouse T cell lymphoma line in culture were studied. Of these four purine nucleosides, deoxyguanosine was the most toxic. At 5 x 10-6 to 10-5 M, deoxyguanosine inhibits growth of the lymphoma cells; higher concentrations result in complete killing. The cytotoxic effects of this deoxynucleoside can be prevented by simultaneous addition to culture medium of deoxycytidine and hypoxanthine. Determination of nucleotide pools in deoxyguanosine-treated cells shows a marked reduction of the deoxycytidine triphosphate and the adenine ribonucleotide pools, accompanied by a sharp rise in the guanosine deoxyribonucleotide and a smaller increase in the corresponding ribonucleotide pools. Deoxyguanosine as well as guanosine, inosine and deoxyinosine were known to accumulate to relatively high levels in the plasma of a patient with T cell immunodeficiency disease associated with purine nucleoside phosphorylase deficiency. The other three purine nucleosides are much less toxic than deoxyguanosine. Thus it is very probable that the patient's clinical manifestations of T lymphocytopenia are the consequence of deoxyguanosine inhibition of lymphoid cell proliferation, resulting from depletion of deoxycytidine triphosphate and adenine nucleotides.

Original languageEnglish (US)
Pages (from-to)523-530
Number of pages8
JournalCell
Volume14
Issue number3
DOIs
StatePublished - 1978
Externally publishedYes

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Purine-Nucleoside Phosphorylase
Deoxyguanosine
Immunosuppression
Toxicity
Lymphocytes
Guanosine
Purine Nucleosides
Ribonucleotides
Inosine
Poisons
T-cells
Deoxyribonucleotides
Deoxycytidine
Hypoxanthine
Adenine Nucleotides
T-Cell Lymphoma
Adenine
Growth
Cell proliferation
Culture Media

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Deoxyguanosine toxicity on lymphoid cells as a cause for immunosuppression in purine nucleoside phosphorylase deficiency. / Chan, Teh sheng.

In: Cell, Vol. 14, No. 3, 1978, p. 523-530.

Research output: Contribution to journalArticle

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