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

Abstract

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.

Authors:
; ;  [1]
  1. (Karolinska Institute, Stockholm (Sweden))
Publication Date:
OSTI Identifier:
6939263
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; (USA); Journal Volume: 166:1
Country of Publication:
United States
Language:
English
Subject:
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

Citation Formats

Karlsson, A., Reichard, P., and Eckstein, F. The metabolism of 3'-azido-2',3'-dideoxyguanosine in CEM cells. United States: N. p., 1990. Web. doi:10.1016/0006-291X(90)91941-K.
Karlsson, A., Reichard, P., & Eckstein, F. The metabolism of 3'-azido-2',3'-dideoxyguanosine in CEM cells. United States. doi:10.1016/0006-291X(90)91941-K.
Karlsson, A., Reichard, P., and Eckstein, F. Mon . "The metabolism of 3'-azido-2',3'-dideoxyguanosine in CEM cells". United States. doi:10.1016/0006-291X(90)91941-K.
@article{osti_6939263,
title = {The metabolism of 3'-azido-2',3'-dideoxyguanosine in CEM cells},
author = {Karlsson, A. and Reichard, P. and Eckstein, F.},
abstractNote = {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.},
doi = {10.1016/0006-291X(90)91941-K},
journal = {Biochemical and Biophysical Research Communications; (USA)},
number = ,
volume = 166:1,
place = {United States},
year = {Mon Jan 15 00:00:00 EST 1990},
month = {Mon Jan 15 00:00:00 EST 1990}
}
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