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

Important note: Information in this article was accurate in 1991. The state of the art may have changed since the publication date.

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

Biochim Biophys Acta. 1991 Jan 10;1091(1):22-8. Unique Identifier : AIDSLINE MED/91137606
Carson DA; Carrera CJ; Wasson DB; Iizasa T; Department of Medicine, University of California, San Diego, La; Jolla.

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.

Keywords: Adenosine Triphosphate/PHYSIOLOGY Antiviral Agents/METABOLISM Arabinonucleosides/METABOLISM Cell Line Deoxyadenosines/*PHARMACOLOGY/TOXICITY Dideoxynucleosides/METABOLISM/PHARMACOLOGY Drug Resistance Enzyme Activation Human HIV/DRUG EFFECTS Purine Nucleosides/METABOLISM/PHARMACOLOGY Purine Nucleotides/METABOLISM Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. T-Lymphocytes/*DRUG EFFECTS/*ENZYMOLOGY 5'-Nucleotidase/*ANALYSIS JOURNAL ARTICLE
910530
M9150268

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