Arabinosyl nucleosides. XXXII. Mechanism of inhibition of L5178y mouse lymphoma cells by 9-beta-D-arabinofuranosylguanine.
The mechanism of the growth-inhibitory action of 9-beta-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 ED50 concentration of 12.3 microM. 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 alpha 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.
D000818:Animals; D001087:Arabinonucleosides / Q000378:metabolism / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis*; D007940:Leukemia L5178 / Q000378:metabolism*; D007942:Leukemia, Experimental / Q000378:metabolism*; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis; D010766:Phosphorylation; D012334:RNA, Neoplasm / Q000096:biosynthesis
D001087:Arabinonucleosides; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C028771:9-arabinofuranosylguanine