Abnormal regulation of purine metabolism in a cultured mouse T-cell lymphoma mutant partially deficient in adenylosuccinate synthetase.

Buddy Ullman, M. A. Wormsted, B. B. Levinson, L. J. Gudas, A. Cohen, S. M. Clift, D. W. Martin

Research output: Contribution to journalArticle

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Abstract

The isolation and characterization of a mutant mouse T-cell lymphoma (S49) with altered purine metabolism is described. This mutant, AU-100, was isolated from a mutagenized population of S49 cells by virtue of its resistance to 0.1 mM 6-azauridine in semisolid agarose. The AU-100 cells are resistant to adenosine mediated cytotoxicity but are extraordinarily sensitive to killing by guanosine. High performance liquid chromatography of AU-100 cell extracts has demonstrated that intracellular levels of GTP, IMP, and GMP are all elevated about 3-fold over those levels found in wild type cells. The AU-100 cells also contain an elevated intracellular level of pyrophosphoribosylphosphate (PPriboseP), which accounts for its resistance to adenosine. However AU-100 cells synthesize purines de novo at a rate less than 35% of that found in wild type cells. Furthermore, the intact cells of this mutant S49 cell line cannot efficiently incorporate labeled hypoxanthine into nucleotides since the salvage enzyme HGPRTase is inhibited in situ. The AU-100 cell line was found to be 80% deficient in adenylosuccinate synthetase, but these cells are not auxotrophic for adenosine or other purines. The significant alterations in the control of purine de novo and salvage metabolism caused by the defect in adenylosuccinate synthetase are mediated by the resulting increased levels of guanosine nucleotides.

Original languageEnglish (US)
Pages (from-to)375-386
Number of pages12
JournalAdvances in Experimental Medicine and Biology
Volume122 A
StatePublished - 1980
Externally publishedYes

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Adenylosuccinate Synthase
T-cells
T-Cell Lymphoma
Metabolism
Adenosine
Salvaging
Purines
Guanosine
Azauridine
Nucleotides
Cells
Inosine Monophosphate
Hypoxanthine
High performance liquid chromatography
Cytotoxicity
Guanosine Triphosphate
Sepharose
Defects
Enzymes
Cell Line

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Ullman, B., Wormsted, M. A., Levinson, B. B., Gudas, L. J., Cohen, A., Clift, S. M., & Martin, D. W. (1980). Abnormal regulation of purine metabolism in a cultured mouse T-cell lymphoma mutant partially deficient in adenylosuccinate synthetase. Advances in Experimental Medicine and Biology, 122 A, 375-386.

Abnormal regulation of purine metabolism in a cultured mouse T-cell lymphoma mutant partially deficient in adenylosuccinate synthetase. / Ullman, Buddy; Wormsted, M. A.; Levinson, B. B.; Gudas, L. J.; Cohen, A.; Clift, S. M.; Martin, D. W.

In: Advances in Experimental Medicine and Biology, Vol. 122 A, 1980, p. 375-386.

Research output: Contribution to journalArticle

Ullman, Buddy ; Wormsted, M. A. ; Levinson, B. B. ; Gudas, L. J. ; Cohen, A. ; Clift, S. M. ; Martin, D. W. / Abnormal regulation of purine metabolism in a cultured mouse T-cell lymphoma mutant partially deficient in adenylosuccinate synthetase. In: Advances in Experimental Medicine and Biology. 1980 ; Vol. 122 A. pp. 375-386.
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