NUCLEIC ACIDS .X. ENZYMATIC HYDROLYSIS OF DINUCLEOSIDE PHOSPHATES CONTAINING ARA-CYTIDINE (CYTARABINE)

Soluble extracts of mouse liver, rabbit liver and rabbit kidney contain an alkaline phosphodiesterase which hydrolyzes the p-nitrophenyl ester of thymidine-5'-phosphate. The kidney and liver preparations have specific activities 30-150 times greater than similar enzyme preparations from KB human epidermoid carcinoma cells or lL1210 mouse leukemia cells. The mouse liver enzyme and rabbit kidney enzyme can hydrolyze 2'-5' linked dinucleoside phosphates containing ara-cytidine. Dinucleoside phosphates linked 3'-5' and 5'-5' are also hydrolyzed by the kidney enzyme. The rate of hydrolysis is greater with 3'-5' linked dinucleoside phosphates than with the 5'-5' and 2'-5' linked compounds. The rate of hydrolysis varies in parallel with the known antiviral activity of the compounds. The data on the enzymatic hydrolysis in vitro tend to support the hypothesis that the antiviral or cytotoxic action of the dinucleoside phosphates containing ara-cytidine is dependent on prior hydrolysis to ara-cytidine. © 1969.