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Related Experiment Videos

Deoxyadenosine-resistant human T lymphoblasts with elevated 5'-nucleotidase activity.

D A Carson1, C J Carrera, D B Wasson

  • 1Department of Medicine, University of California, San Diego, La Jolla.

Biochimica Et Biophysica Acta
|January 10, 1991
PubMed
Summary

A mutant T lymphoblastoid cell line with increased cytosolic 5'-nucleotidase activity showed resistance to deoxyadenosine toxicity. This enhanced enzyme activity impacts purine nucleoside metabolism in T cells.

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Area of Science:

  • Biochemistry
  • Cell Biology
  • Pharmacology

Background:

  • Mammalian cells possess multiple 5 nucleotidase enzymes, but their distinct roles in nucleotide metabolism remain unclear.
  • Deoxyadenosine toxicity poses a challenge, necessitating research into its metabolic pathways and resistance mechanisms.
  • Understanding nucleoside metabolism is crucial for developing targeted therapies.

Purpose of the Study:

  • To investigate the specific function of ATP-activated cytosolic 5 nucleotidase in deoxyadenosine metabolism.
  • To characterize a mutant human T lymphoblastoid cell line (CEM-dAdoR) with elevated cytosolic 5 nucleotidase activity.
  • To elucidate the role of this enzyme in resistance to toxic nucleoside analogs.

Main Methods:

  • Selection of a deoxyadenosine-resistant human T lymphoblastoid cell line (CEM-dAdoR).

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  • Enzyme activity assays to compare cytosolic 5 nucleotidase levels between mutant and parental cells.
  • Metabolic studies using radiolabeled nucleosides (deoxyadenosine, arabinofuranosyladenine, deoxyguanosine, arabinofuranosylguanine, 2 3 -dideoxyadenosine, 2 3 -dideoxyinosine) in the presence of deoxycoformycin.

    • Main Results:

    • The CEM-dAdoR mutant exhibited a 4-fold increase in ATP-activated cytosolic 5 nucleotidase activity compared to parental CEM cells.
    • Mutant cells accumulated fewer nucleotides from deoxyadenosine and 9-beta-D-arabinofuranosyladenine, demonstrating resistance to their toxic effects.
    • Elevated 5 nucleotidase activity correlated with increased formation of 2 3 -dideoxyadenosine and augmented 2 3 -dideoxyadenosine 5 -triphosphate accumulation.

    Conclusions:

    • Cytosolic 5 nucleotidase plays a critical role in the metabolism of purine 2 -deoxyribonucleosides, arabinonucleosides, and 2 3 -dideoxyribonucleosides in T lymphoblasts.
    • Increased cytosolic 5 nucleotidase activity confers resistance to the toxicity of these nucleoside analogs.
    • This finding highlights the enzyme's importance in cellular defense mechanisms against cytotoxic nucleosides.