Advertisement

Thymidine Sensitivity and Deoxynucleotide Pools of Human Lymphoid and Melanoma Cells in Vitro

  • A. Leyva
  • H. Appel
  • H. M. Pinedo
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 165)

Abstract

Exposure of cells to excessive amounts of thymidine (dThd) may cause inhibition of DNA synthesis due to a depletion of deoxycytidine 5′-triphosphate (dCTP). Thymidine 5′-triphosphate (dTTP) accumulates in dThd-treated cells and leads to inhibition of ribonucleotide reductase-mediated synthesis of cytosine deoxynucleotides1. The toxic effects of dThd have been investigated with various mammalian cells in vitro. Notably, lymphoid cells of T-cell origin, but not of B-cell origin, are highly sensitive to dThd2,3. In vitro and in vivo studies have been reported demonstrating the therapeutic potential of high-dose dThd treatment against melanoma4–6. However, no deoxynucleotide metabolism studies on melanoma cells have been reported. In the present study we compared human T- and B- cells and melanoma cells in vitro with respect to dThd sensitivity, deoxynucleotide pool profiles and changes in deoxynucleotide levels in response to dThd.

Keywords

Melanoma Cell High Pressure Liquid Chromatography Nucleotide Pool NC37 Cell Pool Profile 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    P. Reichard, From deoxynucleotides to DNA synthesis, Fed. Proc. 37: 9 (1978).PubMedGoogle Scholar
  2. 2.
    D.A. Carson, J. Kaye, and J.E. Seegmiller, Differential sensitivity of human leukemic T cell lines and B cell lines to growth inhbition by deoxyadenosine, J. Immunol. 121: 1726 (1978).PubMedGoogle Scholar
  3. 3.
    D.W. Kufe, P. Beardsley, D. Karp, L. Parker, A. Rosowsky, G. Canellos, and E. Frei III, High-dose thymidine infusions in patients with leukemia and lymphoma, Blood 55: 580 (1980).PubMedGoogle Scholar
  4. 4.
    S.S. Lee, B.C. Giovanella, and J.S. Stehlin, Selective lethal effect of thymidine on human and mouse tumor cells, J. Cell. Physiol. 29: 401 (1977).CrossRefGoogle Scholar
  5. 5.
    S.S. Lee, B.C. Giovanella, and J.S. Stehlin, Effect of excess thymidine on the growth of human melanoma cells transplanted in thymus-deficient nude mice, Cancer Lett. 3: 209 (1977).PubMedCrossRefGoogle Scholar
  6. 6.
    S.B. Howell, R.S. Jenkins, and J. Streifel, Activity of thymidine as a chemotherapeutic agent against human tumor xenografts in nude mice, Cancer Res. 39: 3875 (1979).PubMedGoogle Scholar
  7. 7.
    A. Leyva, H. Appel, P. Smith, J. Lankelma, and H.M. Pinedo, Inhibition of cell growth by N-(phosphonacetyD-L-aspartate in human and murine cells in vitro, Cancer Lett. 12: 169 (1981).PubMedCrossRefGoogle Scholar
  8. 8.
    A. Leyva, H. Appel, and H.M. Pinedo, Purine modulation of thymidine activity in L1210 leukemia cells in vitro, Leukemia Res., in press.Google Scholar
  9. 9.
    S.B. Howell, R. Taetle, and J. Mendelsohn, Thymidine as a chemotherapeutic agent: sensitivity of normal human marrow, peripheral blood T cells, and acute nonlymphocytic leukemia, Blood 55: 505 (1980).PubMedGoogle Scholar
  10. 10.
    D.A. Carson, J. Kaye, S. Matsumato, J.E. Seegmiller, and L. Thompson, Biochemical basis for the enhanced toxicity of deoxyribonucleosides toward malignant human T cell lines, Proc. Natl. Acad. Sci. U.S.A. 76: 2430 (1979).PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • A. Leyva
    • 1
    • 2
  • H. Appel
    • 1
    • 2
  • H. M. Pinedo
    • 1
    • 2
  1. 1.Section of Experimental Chemotherapy, Netherlands Cancer InstituteFree University HospitalAmsterdamThe Netherlands
  2. 2.Department of OncologyFree University HospitalAmsterdamThe Netherlands

Personalised recommendations