Abstract
In response to inhibition of purine de novo biosynthesis by methotrexate (MTX), an increase in the availability of 5-phosphoribosyl-1-pyrophosphate (PRPP) occurs. As a result of this increased availability of PRPP, potentiation of 6-mercaptopurine (6MP) incorporation can be expected in cells with an active purine de novo synthesis (Fig.1).
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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).
E. Cadman, R. Heimer and L. David, Enhanced 5-fluorouracil nucleotide formation after methotrexate administration: explanation for drug synergism, Science 205: 1135 (1979).
J.P.M. Bökkerink, T.J. Schouten, R.A. De Abreu, R.J.J. Lippens, G.A.M. de Vaan, C.H.M.M. de Bruyn en J.P.R.M. van Laarhoven, 6-Mercaptopu-rine en methotrexate, zicht op een rationeel gebruik na 35 jaar? T.Kindergeneesk. 52: 118 (1984).
G.J. Peters, A. Oosterhof and J.H. Veerkamp, Metabolism of phosphori-bosyl pyrophosphate in peripheral and phytohemagglutinin-stimulated mammalian lymphocytes, Int.J.Biochem. 13: 577 (1981).
H. Becher, M. Weber and G.W. Lohr, Purine nucleotide synthesis in normal and leukemic blood cells, Klin.Wschr., 56: 275 (1978).
J.R. Bertino, W.L. Sawicki, C. Linquist and V.S. Gupta, Schedule-dependent antitumor effects of methotrexate and 5-fluorouracil, Cancer Res. 37: 327 (1977).
D.W. Kufe and M. Egan, Enhancement of 5-fluorouracil incorporation into human lymphoblast ribonucleic acid, Biochem.Pharmacol. 30: 129 (1981).
C. Benz and E. Cadman, Modulation of 5-fluorouracil metabolism and cytotoxicity by antimetabolite pretreatment in human colorectal adenocarcinoma HCT-8, Cancer Res. 41: 994 (1981).
R.D. Armstrong, R. Vera, P. Snyder and E. Cadman, Enhancement of 6-thio-guanine cytotoxic activity with methotrexate, Biochem.Biophys.Res. Comm. 109: 595 (1982).
G.P. Browman, Clinical application of the concept of methotrexate plus 5-FU sequence-dependent “synergy”: How good is the evidence?, Cancer Treat.Rep. 68: 465 (1984).
S.B. Kaye, G. Sangster, A. Hutcheon, T. Habeshaw, F. Crossling, C. Ferguson, C. McArdle, D. Smith, W.D. George and K.C. Caiman, Sequential methotrexate plus 5-FU in advanced breast and colorectal cancers: a phase II study, Cancer Treat.Rep. 68: 547 (1984).
R. Hermann, C. Manegold, M. Schroeder, F.J. Tigges, H. Bartsch, F. Jungi and D. Fritze, Sequential methotrexate and 5-FU in breast cancer resistant to the conventional application of these drugs, Cancer Treat.Rep. 68: 1279 (1984).
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© 1986 Plenum Press, New York
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Bökkerink, J.P.M. et al. (1986). Increased Availability of Phosphoribosyl Pyrophosphate as the Basis for Enhanced 6-Mercaptopurine Incorporation by Methotrexate, in Cultured Human 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_21
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DOI: https://doi.org/10.1007/978-1-4684-1248-2_21
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