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.

[1]  J. Keller,et al.  Some effects of D-arabinosyl nucleosides on polymer syntheses in mouse fibroblasts. , 1966, Cancer research.

[2]  P. Calabresi,et al.  Biochemical and pharmacological studies with 1-beta-D-arabinofuranosylcytosine in man. , 1966, Biochemical pharmacology.

[3]  G. Lepage,et al.  Inhibitory effects of the arabinosides of 6-mercaptopurine and cytosine on purine and pyrimidine metabolism. , 1966, Cancer research.

[4]  P. Carbone,et al.  Cytogenetic and morphologie abnormalities in human bone marrow cells during cytosine arabinoside therapy. , 1966, Blood.

[5]  C. G. Smith,et al.  Studies of the enzymatic deamination of cytosine arabinoside. I. Enzyme distribution and species specificity. , 1967, Biochemical pharmacology.

[6]  S. Silagi.  Metabolism of 1-beta-D-arabinofuranosylcytosine in L cells. , 1965, Cancer research.

[7]  Adamson Rh,et al.  Antitumor activity and pharmacologic disposition of cytosine arabinoside (NSC-63878). , 1965 .

[8]  C. Dekker.  Separation of nucleoside mixtures on Dowex-1 (OH-). , 1965, Journal of the American Chemical Society.

[9]  R. Tye,et al.  LIQUID SCINTILLATION COUNTING OF CARBON-14 IN AQUEOUS DIGESTS OF WHOLE TISSUES. , 1965, Analytical chemistry.

[10]  I. Wodinsky,et al.  Activity of cytosine arabinoside (NSC-63878) in a spectrum of rodent tumors. , 1965, Cancer chemotherapy reports.

[11]  M. Chu,et al.  COMPARATIVE STUDIES OF LEUKEMIC CELLS SENSITIVE AND RESISTANT TO CYTOSINE ARABINOSIDE. , 1965, Biochemical pharmacology.

[12]  R. Adamson,et al.  Antitumor activity and pharmacologic disposition of cytosine arabinoside (NSC-63878). , 1965, Cancer chemotherapy reports.

[13]  M. L. Eidinoff,et al.  ACTION OF 1-BETA-D-ARABINOFURANOSYLCYTOSINE ON THE NUCLEIC ACID METABOLISM AND VIABILITY OF HELA CELLS. , 1965, Cancer research.

[14]  J. Evans,et al.  The Effect of 1-β-d-Arabinofuranosylcytosine Hydrochloride on Murine Neoplasms , 1964 .

[15]  G. Mengel,et al.  THE REVERSAL OF CYTOSINE ARABINOSIDE ACTIVITY IN VIVO BY DEOXYCYTIDINE. , 1964, Biochemical pharmacology.

[16]  V. Vaitkevicius,et al.  Megaloblastosis Produced by a Cytosine Antagonist , 1963 .

[17]  M. Chu,et al.  A proposed mechanism of action of 1-beta-D-arabinofuranosyl-cytosine as an inhibitor of the growth of leukemic cells. , 1962, Biochemical pharmacology.

[18]  L. Pizer,et al.  Metabolism of pyrimidine arabinonucleosides and cyclonucleosides in Escherichia coli. , 1960, The Journal of biological chemistry.

[19]  J. Møller,et al.  Chromatographic Separations of Cytosine Containing Compounds. , 1958 .