Sparing Action of Uridine on the Activity of Arabinosylcytosine with Normal and Leukemic Mice

Uridine, administered in conjunction with a suboptimal dose of 1-β-d-arabinofuranosylcytosine (ara-C), resulted in prolonged survival of BDF1 mice bearing Leukemia L1210 in comparison with administration of ara-C alone. Daily treatment of mice with ara-C after inoculation of Leukemia L1210, resulted in an increase in life-span of 200% with 14 mg/kg and over 800% with 20 mg/kg while concurrent treatment with uridine (480 mg/kg) and ara-C (14 mg/kg) produced an increase in life-span of over 600%. No potentiation occurred when uridine was replaced by thymidine, 1-β-d-arabinofuranosyluracil, or several other uracil metabolites. Administration of uridine with an optimal level of ara-C produced toxicity in normal mice. In normal mice, an increase of 117% in radioactivity of spleen was observed 60 min after concurrent administration of uridine and ara-C-3H as compared with ara-C-3H alone. With either regimen, the major portions of the radioactivity of spleens were characterized as ara-C after fractionation by column chromatography. The radiochemical results provide a possible explanation for the sparing action of uridine in conjunction with a suboptimal dose of ara-C.