Enhanced uridine kinase in rat liver following 5-azacytidine administration. In vivo characterization and properties of partially purified enzyme.

The activity of uridine kinase in rat liver is markedly enhanced following the intraperitoneal administration of 5azacytidine by a process independent of adrenal secretion. The enhancement of enzyme activity is dose-dependent and is maximal at 24 to 28 hours following the administration of the analogue. The increase of uridine kinase in the liver is unaffected by a number of compounds interfering with DNA, RNA, and protein synthesis. Only cytidine and uridine administered in excess simultaneously with 5-azacytidine reverse the effect of the drug. Multiple doses of S-azacytidine increase the activity of uridine kinase 4to Sfold followed by its subsequent decrease. The renewed enhancement of the enzyme activity is possible by further administrations of the drug. From the effect of actinomycin D, the calculated half-time of template RNA for liver uridine kinase is about 24 hours. Partially purified uridine kinase from the liver of S-azacytidine-treated rats differs from the control enzyme preparation by its higher stability toward heating.