Skip to main content

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

Medical Oncology and Tumor Pharmacotherapy volume 7, pages 223–226 (1990)Cite this article

Abstract

1-B-D-arabinofuranosylcytosine-573′-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 deoxyribonucleo-side 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.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

43,34 €

Price includes VAT (Finland)
Tax calculation will be finalised during checkout.

References

  1. Higashigawa M, Ochiai H, Ohkubo T, Kawasaki H, Nobori T, Kamiya H, Sakurai M: Incorporation of N4behenoyl-1-B-D-arabinofuranosylcytosine into DNA as 1-B-D-arabinofuranosylcytosine.Med Oncol & Tumor Pharmacother 5, 265 (1988).

    CAS  Google Scholar 

  2. Ellison R R, Holland J F, Weil M, Jacpuillat C, Boiron M, Bernard J, Sawitsky A, Rosner F, Gussoff B, Silver R T, Karanas A, Cuttner J, Spurr C L, Hayes D M, Blom J, Leone L A, Haurani F, Kyle R, Flutchison J L, Forcier R J, Moon J H: Arabinosyl cytosine: a useful agent in the treatment of acute leukemia in adults.Blood 32, 507 (1968).

    PubMed  CAS  Google Scholar 

  3. Ho D H W, Frei E III: Clinical pharmacology of l-B- D-arabinofuranosylcytosine.Clin Pharmac Ther 12, 944 (1971).

    CAS  Google Scholar 

  4. Saneyoshi M, Morozumi M, Kodama K, Machida H, Kuninaka A, Yoshino H: Synthetic nucleosides and nucleotides. XVI. Synthesis and biological evaluation of a series of l-B-D-arabinofuranosylcytosine 5′-alkyl or arylphosphates.Chem Pharmac Bull 28, 2915 (1980).

    CAS  Google Scholar 

  5. Sato T, Morozumi M, Kodama K, Kuninaka A, Yoshino H: Sensitive radioimmunoassay for cytosine and uracil arabinoside in plasma.Cancer Treat Res 68, 1357 (1984).

    CAS  Google Scholar 

  6. Khym J X: An analytical system for rapid separation of tissue nucleotides at low pressures of conventional anion exchangers.Clin Chem 21, 1245 (1975).

    PubMed  CAS  Google Scholar 

  7. Garrett C, Santi D V: A rapid and sensitive high pressure liquid chromatography assay for deoxyribo-nucleoside triphosphates in cell extracts.Analyt Biochem 99, 268 (1979).

    PubMed  Article  CAS  Google Scholar 

  8. Higashigawa M, Ido M, Ohkubo T, Kawasaki H, Kamiya H, Sakurai M, Taniguchi K, Hamazaki M: Increased sensitivity to l-B-D-arabinofuranosylcytosine in P388 murine leukemic cells resistant to etoposide.Leuk Res 13, 39 (1989).

    PubMed  Article  CAS  Google Scholar 

  9. Coleman C, Stoller R G, Drake J C, Chabner B A: Deoxycytidine kinase: properties of the enzyme from human leukemic granulocytes.Blood 46, 791 (1975).

    PubMed  CAS  Google Scholar 

  10. Furth J J, Cohen S S: Inhibition of mammalian DNA Polymerase by the 5′-triphosphate of 1-B-D-arabinofuranosylcytosine and the 5′-triphosphate of 9-B-D-arabinofuranosyladenosine.Cancer Res 28, 2061 (1968).

    PubMed  CAS  Google Scholar 

Download references

Author information

Affiliations

  1. Department of Pediatrics, Mie University School of Medicine, 2-174, Edobashi, Tsucity, 514, Mieken, Japan

    Masamune Higashigawa, Hiroki Hori, Toshiki Ohkubo, Hajime Kawasaki, Tamotu Yoshizumi & Minoru Sakurai

Authors
  1. Masamune Higashigawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hiroki Hori
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Toshiki Ohkubo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hajime Kawasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Tamotu Yoshizumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Minoru Sakurai
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Higashigawa, M., Hori, H., Ohkubo, T. et al. 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. 7, 223–226 (1990). https://doi.org/10.1007/BF02987099

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02987099

Key words

  • 1-B-Darabinofuranosyl cytosine-5′-stearylphosphate (C18PCA)
  • Ara-C
  • Ara-CTP
  • dNTP