The metabolism of 3'-azido-2',3'-dideoxyguanosine in CEM cells

Journal Article · Mon Jan 15 00:00:00 EST 1990 · Biochemical and Biophysical Research Communications; (USA)

DOI:https://doi.org/10.1016/0006-291X(90)91941-K· OSTI ID:6939263

Karlsson, A; Reichard, P; Eckstein, F ^[1]

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1. Karolinska Institute, Stockholm (Sweden)

When CEM cells were incubated with ({sup 3}H)-labeled 3'-azido-2',3'-dideoxyguanosine (AzddGuo), the isotope was largely recovered as ribo- and deoxyribonucleotides in the acid soluble fraction of CEM cells, due to extensive catabolism of AzddGuo and recycling of the guanine formed by purine nucleoside phosphorylase. Only 10% was found as the AzddGuo nucleotides, with the diphosphate of AzddGuo as the dominating nucleotide at all time points. Thus nucleoside diphosphate kinase was rate limiting for the formation of AzddGuo triphosphate, responsible for the toxic and antiviral activity of the nucleoside. Inhibition of de novo deoxyribonucleotide synthesis with hydroxyurea increased the phosphorylation of AzddGuo twofold.

• OSTI ID: 6939263
• Journal Information: Biochemical and Biophysical Research Communications; (USA), Vol. 166:1; ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
NUCLEOTIDES
METABOLISM
HYDROXYUREA
INHIBITION
LEUKEMIA
PHOSPHORYLATION
TRACER TECHNIQUES
TRITIUM COMPOUNDS
TUMOR CELLS
AMIDES
ANIMAL CELLS
CHEMICAL REACTIONS
DISEASES
HEMIC DISEASES
HYDROGEN COMPOUNDS
HYDROXY COMPOUNDS
IMMUNE SYSTEM DISEASES
ISOTOPE APPLICATIONS
NEOPLASMS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
550501* - Metabolism- Tracer Techniques