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Synergism Between Purines and Thymidine (TDR) in Reversal of Methotrexate (MTX) Toxicity in Mice Using Continuous Infusions

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Purine Metabolism in Man-IV

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 165))

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Abstract

Methotrexate (MTX), a widely used drug in antineoplastic therapy, is a competitive inhibitor of dihydrofolate reductase. Inhibition of this enzyme leads to depletion of tetrahydrofolic acid which plays an important role in the de novo synthesis of purines and thymidylate. When MTX is used at high doses, it is mandatory that an effective procedure is used to prevent irreversible toxic damage to normal tissues. Coadministration of thymidine (TdR) and purines have been used in mouse model studies for this purpose, but the results have been conflicting1,2. The purpose of this study was to investigate the role of purine in the reversal by TdR of MTX toxicity. As a model system, continuous i.v. infusion of MTX, TdR and inosine (Ino) into mice was chosen, since it allows the establishment of constant plasma levels similar to cell culture conditions.

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References

  1. K.R. Harrap, G.A. Taylor and G.P. Browman, Chem.-Biol.Interact., 18: 119 (1977).

    Article  PubMed  CAS  Google Scholar 

  2. J.H. Semon and G.B. Grindey, Cancer Res., 38: 2905 (1978).

    PubMed  CAS  Google Scholar 

  3. M.A. Paul and C. Dave, Proc.Soc.Exp.Biol.Med., 148: 118 (1975).

    PubMed  CAS  Google Scholar 

  4. A. Leyva, J. Schornagel and H.M. Pinedo, Adv.Exp.Med.Biol., 122B: 389 (1980).

    Article  CAS  Google Scholar 

  5. C. Garrett and D.V. Santi, Anal.Biochem., 99: 268 (1979).

    Article  PubMed  CAS  Google Scholar 

  6. A. Leyva, H. Appel and H.M. Pinedo, Leukemia Res., in press.

    Google Scholar 

  7. T.D.V. Swinscow, “Statistics at Square One”, The British Medical Association, London (1978).

    Google Scholar 

  8. H.M. Pinedo, D.S. Zaharko and R.L. Dedrick, Cancer Treat.Rep., 60: 889 (1976).

    PubMed  CAS  Google Scholar 

  9. M.H.N. Tattersall, B. Brown and E. Frei III, Nature, 253: 198 (1975).

    Article  PubMed  CAS  Google Scholar 

  10. J.A. Straw, D.C. Talbot, G.A. Taylor and K.R. Harrap, J.Natl. Cancer Inst., 58: 91 (1977).

    PubMed  CAS  Google Scholar 

  11. U.A.S. Al-Khalidi and T.H. Chaglassian, Biochem.J., 97: 318 (1965).

    PubMed  CAS  Google Scholar 

  12. J.H. Schornagel, M.P. Uitendaal, A. Leyva and H.M. Pinedo, in preparation.

    Google Scholar 

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Author information

Authors and Affiliations

  1. Netherlands Cancer Institute, Free University, Amsterdam, The Netherlands

    Martin P. Uitendaal, Jan H. Schornagel, Albert Leyva & Herbert M. Pinedo

  2. State University, Utrecht, The Netherlands

    Martin P. Uitendaal, Jan H. Schornagel, Albert Leyva & Herbert M. Pinedo

Authors
  1. Martin P. Uitendaal
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  2. Jan H. Schornagel
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  3. Albert Leyva
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  4. Herbert M. Pinedo
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Editor information

Editors and Affiliations

  1. University of Nijmegen Faculty of Medicine, Nijmegen, The Netherlands

    Chris H. M. M. De Bruyn

  2. Guy’s Hospital Medical School, London, UK

    H. Anne Simmonds

  3. University of Vienna, Vienna, Austria

    Mathias M. Müller

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© 1984 Springer Science+Business Media New York

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Uitendaal, M.P., Schornagel, J.H., Leyva, A., Pinedo, H.M. (1984). Synergism Between Purines and Thymidine (TDR) in Reversal of Methotrexate (MTX) Toxicity in Mice Using Continuous Infusions. In: De Bruyn, C.H.M.M., Simmonds, H.A., Müller, M.M. (eds) Purine Metabolism in Man-IV. Advances in Experimental Medicine and Biology, vol 165. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-0390-0_76

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  • DOI: https://doi.org/10.1007/978-1-4757-0390-0_76

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-0392-4

  • Online ISBN: 978-1-4757-0390-0

  • eBook Packages: Springer Book Archive

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