Competitive Inhibition of Uridine Incorporation by 6-Azauridine in Uninfected and Mengovirus-Infected Novikoff Hepatoma Cells 1

Summary

The incorporation of uridine into cellular RNA or viral RNA by uninfected and mengovirus-infected Novikoff rat hepatoma cells (line N1S1-67) is inhibited about 90% by 24 mM 6-azauridine in the medium. This inhibition is a direct consequence of an interference by azauridine with the conversion of uridine to free nucleotides and is not a reflection of an inhibition of RNA synthesis. Azauridine acts as competitive inhibitor of both the entry of uridine into the cell and its subsequent phosphorylation to UMP. Both, host cell and viral RNA synthesis are highly resistant to inhibition by azauridine as measured by the incorporation of adenosine, and the production of virusinduced RNA polymerase and mature virus are also not affected by 24 mM azauridine. The resistance of the cells to azauridine appears to be related to a failure of the cells to accumulate significant amounts of azaUMP, not because they lack uridine kinase but probably because azauridine uptake or phosphorylation is under some regulatory control.

The authors thank John Erbe for valuable technical assistance.