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Arabinosyl nucleosides. XXXII. Mechanism of inhibition of L5178y mouse lymphoma cells by 9-β-D-arabinofuranosylguanine

Authors
Journal
Chemico-Biological Interactions
0009-2797
Publisher
Elsevier
Publication Date
Volume
34
Issue
3
Identifiers
DOI: 10.1016/0009-2797(81)90102-2
Disciplines
  • Biology

Abstract

Abstract The mechanism of the growth-inhibitory action of 9-β-D-arabinofuranosylguanine (ara-G) on mouse lymphoma cells (L5178y) at the level of nucleic acid synthesis was studied. Ara-G inhibits the cell proliferation at an ED 50 concentration of 12.3 μM. The cells die because of unbalanced growth. At cytostatic concentrations ara-G inhibits the incorporation rate of dThd into DNA to a much higher degree compared to those of the precursors into RNA or proteins. Ara-G has no effect on the induction of DNA polymerase α occurring at the beginning of the S-phase; this compound exerts its inhibitory activity during the S-phase. Ara-G is intracellularly phosphorylated to ara-GTP. It was demonstrated that ara-G is incorporated into DNA but not into RNA; one molecule of ara-G is incorporated per 7050 molecules of deoxyguanosine. The ara-GMP moieties, incorporated into DNA of L5178y cells are not removed during a culture period of 7.7 doubling steps; compared to the controls no reduction of the viability and growth rate was observed.

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