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

  • Martin P. Uitendaal
  • Jan H. Schornagel
  • Albert Leyva
  • Herbert M. Pinedo
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 165)

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.

Keywords

Dihydrofolate Reductase Cell Culture Condition Rescue Agent DBA2 Mouse Mouse Model Study 
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.

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Copyright information

© Springer Science+Business Media New York 1984

Authors and Affiliations

  • Martin P. Uitendaal
    • 1
    • 2
  • Jan H. Schornagel
    • 1
    • 2
  • Albert Leyva
    • 1
    • 2
  • Herbert M. Pinedo
    • 1
    • 2
  1. 1.Netherlands Cancer InstituteFree UniversityAmsterdamThe Netherlands
  2. 2.State UniversityUtrechtThe Netherlands

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