The effect of the cytostatic agent 9-α- d-arabinofuranosyladenine on the nucleic acid metabolism in L5178 Y cells

Abstract

The influence of 9-α- d-arabinofuranosyladenine (α-araAdo) on cell metabolism of mouse lymphoma cells (L5178y) has been studied on cellular as well as on subcecllular level. α-AraAdo strongly inhibits the cell proliferation of L5178y cells. Starting with 3 × 10 3 cells/ml and an incubation period of 72 hr, the drug reduces the cell proliferation to 50 per cent at a concentration of 12 μM. The cells die because of “unbalanced growth”. The cytostatic effect of α-araAdo can be abolished by coincubation with deoxyadenosine but not by adenosine. At cytostatic concentrations α-araAdo inhibits selectively the incorporation rate of thymidine into DNA but not the incorporation rates of precursors into RNA or protein. α-AraAdo is intracellularly phosphorylated to α-araATP. The compound has no effect on the extent of intracellular phosphorylation of exogenous administered adenosine or deoxyadenosine. α-AraAdo is incorporated into DNA but not into RNA; one molecule of α-araAdo is incorporated per 14,000 molecules of deoxyadenosine.