Deoxyribonucleoside triphosphate pools and Ara-CTP levels in P388 murine leukemic cells treated with 1-B-D-arabinofuranosylcytosine-5'-stearylphosphate which is a newly synthesized derivative of 1-B-D-arabinofuranosylcytosine

Med Oncol Tumor Pharmacother. 1990;7(4):223-6. doi: 10.1007/BF02987099.

Abstract

1-B-D-arabinofuranosylcytosine-5'-stearylphosphate (C18PCA), which is an Ara-CMP ester and one of the most promising orally effective anti-leukemic drugs, is a newly synthesized derivative of Ara-C. The antitumor effect of C18PCA and Ara-C was investigated against the P388 ascites tumor in BDF1 mice. Treatment with C18PCA (100 mg kg-1, orally) and Ara-C (40 mg kg-1, subcutaneously) was administered on days 1, 3 and 5 after tumor inoculation. The percentage increase in lifespans of the mice treated with C18PCA or Ara-C were 84.4% and 53.9%, respectively. The determination of the plasma Ara-C concentration revealed that the plasma concentration of Ara-C was retained much longer in mice which orally received C18PCA than in those which received Ara-C. By using high-performance liquid chromatography, it was revealed that the deoxyribonucleoside triphosphate pools increased gradually but Ara-CTP concentration once increased, then decreased rapidly when Ara-C was administered subcutaneously. On the other hand, both the intracellular deoxyribonucleoside triphosphate (dNTP) pools and Ara-CTP level increased gradually after oral administration of C18PCA. We concluded that these longer-term biochemical effects, even if the plasma concentration of Ara-C and Ara-CTP level were low, might be correlated with antitumor effects of C18PCA.

MeSH terms

  • Administration, Oral
  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology
  • Arabinofuranosylcytosine Triphosphate / metabolism*
  • Arabinonucleotides / pharmacology*
  • Chromatography, High Pressure Liquid
  • Cytarabine / administration & dosage
  • Cytarabine / blood
  • Cytarabine / pharmacology
  • Cytidine Monophosphate / analogs & derivatives*
  • Cytidine Monophosphate / pharmacology
  • Deoxyribonucleotides / metabolism*
  • Leukemia P388 / drug therapy*
  • Leukemia P388 / metabolism*
  • Male
  • Mice

Substances

  • Antineoplastic Agents
  • Arabinonucleotides
  • Deoxyribonucleotides
  • Cytarabine
  • Arabinofuranosylcytosine Triphosphate
  • 1-arabinofuranosylcytosine-5'-stearylphosphate
  • Cytidine Monophosphate