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

Biochim Biophys Acta. 1991 Jan 10;1091(1):22-8. doi: 10.1016/0167-4889(91)90216-k.

Abstract

Although several different enzymes with 5'-nucleotidase activity have been described in mammalian cells, their functions in nucleotide metabolism have not been clearly distinguished. In the present experiments, a mutant human T lymphoblastoid cell line (CEM-dAdoR) was selected specifically for resistance to deoxyadenosine toxicity. Compared to parental CEM cells, the variant had 4-fold elevated ATP-activated cytosolic 5'-nucleotidase activity. Other enzymes of potential importance for deoxyadenosine metabolism were indistinguishable in the two cell types. In medium supplemented with the adenosine deaminase inhibitor deoxycoformycin, the T cells with increased 5'-nucleotidase accumulated less nucleotides from exogenously added deoxyadenosine, or 9-beta-D-arabinofuranosyladenine, than did parental T lymphocytes. These metabolic changes were associated with resistance to the growth inhibitory effects of these nucleosides, and also to deoxyguanosine and to 9-beta-D-arabinofuranosylguanine. The T cells with elevated 5'-nucleotidase activity formed more 2',3'-dideoxyadenosine than did parental cells, in deoxycoformycin-supplemented medium. The accumulation of 2',3'-dideoxyadenosine 5'-triphosphate from 2',3'-dideoxyinosine was similarly augmented in the mutant. These data establish the importance of the cytosolic 5'-nucleotidase for the metabolism of purine 2'-deoxyribonucleosides, arabinonucleosides and 2',3'-dideoxyribonucleosides in T lymphoblasts.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 5'-Nucleotidase / analysis*
  • Adenosine Triphosphate / physiology
  • Antiviral Agents / metabolism
  • Arabinonucleosides / metabolism
  • Cell Line
  • Deoxyadenosines / pharmacology*
  • Deoxyadenosines / toxicity
  • Dideoxynucleosides / metabolism
  • Dideoxynucleosides / pharmacology
  • Drug Resistance
  • Enzyme Activation
  • HIV / drug effects
  • Humans
  • Purine Nucleosides / metabolism
  • Purine Nucleosides / pharmacology
  • Purine Nucleotides / metabolism
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / enzymology*

Substances

  • Antiviral Agents
  • Arabinonucleosides
  • Deoxyadenosines
  • Dideoxynucleosides
  • Purine Nucleosides
  • Purine Nucleotides
  • Adenosine Triphosphate
  • 5'-Nucleotidase