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Purine and Pyrimidine Metabolism in Man V pp 129–134Cite as

Synergy of Methotrexate and 6-Mercaptopurine on Cell Growth and Clono- Genicity of Cultured Human T-Lymphoblasts

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Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 195B))

Abstract

Methotrexate (MTX) is a well known inhibitor of purine de novo synthesis and thymidylate synthesis. In cells with an active purine de novo synthesis 5-phosphoribosyl-1-pyrophosphate (PRPP) levels are increased significantly, when the cells are exposed to MTX.1.2 Enhanced incorporation of 6-mercaptopurine (6MP) is observed, when 6MP is added at points of time at which PRPP levels are maximal.3 These observations indicate to a possible synergistic action of MTX and 6MP under these circumstances. Therefore, we measured the effects of MTX and 6MP on cell growth, cell viability and clonogenic activity of MOLT 4 cells under conditions at which 6MP incorporation is enhanced in these cells after pretreatment with MTX.

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References

  1. J. M. Buesa-Perez, A. Leyva and H. M. Pinedo, Effect of methotrexate on 5-phosphoribosyl-1-pyrophosphate levels in L1210 leukemia cells in vitro; Cancer Res. 40: 139 (1980).

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  2. E. Cadman, R. Heimer and L. Davis, Enhanced 5-fluorouracil nucleotide formation after methotrexate administration: explanation for drug synergism, Science 205: 1135 (1979).

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  4. J. P. M. Bökkerink, R. A. De Abreu, J. P. R. M. van Laarhoven, M. A. H. Bakker, T. W. Hulscher, E. D. A. M. Schretlen and C. H. M. M. de Bruijn, Increased availability of phosphoribosyl pyrophosphate as the basis for enhanced 6-mercaptopurine incorporation by methotrexate, in cultured human lymphoblasts, submitted for publication in: Purine Metabolism in Man-V.

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  5. R. A. De Abreu, J. P. M. Bökkerink, M. A. H. Bakker, T. W. Hulscher, J. M. van Baal, C. H. M. M. de Bruijn and E. D. A. M. Schretlen, Influence of methotrexate on purine and pyrimidine pools and on cell phase distribution of cultured human lymphoblasts, Submitted for publication in: Purine Metabolism in Man-V.

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Author information

Authors and Affiliations

  1. Centre for Pediatric Oncology SE Netherlands, Dept.of Pediatrics, University Hospital St.Radboud, Nijmegen, The Netherlands

    Ronney A. De Abreu, Jos P. M. Bökkerink, Marinka A. H. Bakker, Tilly W. Hulscher, Gerard A. M. de Vaan, Chris H. M. M. de Bruijn & Egbert D. A. M. Schretlen

Authors
  1. Ronney A. De Abreu
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  2. Jos P. M. Bökkerink
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  3. Marinka A. H. Bakker
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  4. Tilly W. Hulscher
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  5. Gerard A. M. de Vaan
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  6. Chris H. M. M. de Bruijn
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  7. Egbert D. A. M. Schretlen
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Editor information

Editors and Affiliations

  1. University of California, San Diego La Jolla, California, USA

    W. L. Nyhan

  2. Scripps Clinic and Research Foundation, La Jolla, California, USA

    L. F. Thompson

  3. M. R. C. Clinical Research Center, Harrow, UK

    R. W. E. Watts

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© 1986 Plenum Press, New York

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De Abreu, R.A. et al. (1986). Synergy of Methotrexate and 6-Mercaptopurine on Cell Growth and Clono- Genicity of Cultured Human T-Lymphoblasts. In: Nyhan, W.L., Thompson, L.F., Watts, R.W.E. (eds) Purine and Pyrimidine Metabolism in Man V. Advances in Experimental Medicine and Biology, vol 195B. Springer, New York, NY. https://doi.org/10.1007/978-1-4684-1248-2_20

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  • DOI: https://doi.org/10.1007/978-1-4684-1248-2_20

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  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4684-1250-5

  • Online ISBN: 978-1-4684-1248-2

  • eBook Packages: Springer Book Archive

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