Arabinosyl nucleosides. XII. Influence of arabinofuranosylthymine on growth of L5178y cells

The antibiotic 1β-D-arabinofuranosylthymine (araThd) is a potent inhibitor of the growth of mouse lymphoma cells (L5178y). The ED₅₀ concentration was found to be 9.8 μM. The cells die as a consequence of an unbalanced growth. The cytostatic activity of araThd can be abolished by coincubation with dThd and dUrd but not with Urd.At cytostatic concentrations araThd selectively blocks DNA synthesis; RNA- and protein synthesis are unaffected. Intracellularly araThd is rapidly phosphorylated to araTTP. This enzymic phosphorylation does not influence the synthesis of the naturally occuring, related triphosphate dTTP.AraTMP is incorporated into DNA during DNA synthesis; 1 mol of araTMP is incorporated/19, 500 molecules of dTMP.