Skip to main content
SpringerLink
Log in

Biochemical Modulation of Pyrimidine Pools for Enhancement of Antipyrimidine Cytotoxicity

  • Chapter
Biochemical Modulation of Anticancer Agents: Experimental and Clinical Approaches

Part of the book series: Developments in Oncology ((DION,volume 47))

Abstract

Biochemical modulation in cancer therapy focuses on the improvement of the therapeutic index of a known anticancer drug (called the effector agent) through the pharmacologic manipulation of appropriate intracellular metabolic pathways by either an anti-metabolite or a metabolite (called the modulating agent) to produce either the selective enhancement of the antitumor effect or the selective protection of the host from the effector agent. For example, certain antipyrimidine effector agents must be activated intracellularly by anabolism to the fraudulent pyr imidine nucleotide analogues in order to exert cytotoxicity. Since these antipyrimidines must successfully compete at each step in their metabolic conversion with the normal pyrimidine counterparts, a modulating agent that selectively lowers the pools of the competing normal intracellular pyrimidines in the tumor can facilitate the targeting of the fraudulent pyrimidines to their effector sites, and thereby enhance their antitumor activity.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Martin DS, Stolfi RL, Spiegelman S: Striking augmentation of the in vivo anticancer activity of 5-fluorouracil (5-FU) by combination with pyrimidine nucleosides: An RNA effect. Proc. Am. Assoc. Cancer Res. 19: 221, 1978.

    Google Scholar 

  2. Spiegelman S, Sawyer R, Nayak R et al: Improving the antitumor activity of 5-fluorouracil by increasing its incorporation into RNA via metabolic modulation. Proc. Natl. Acad. Sci., USA 77: 4966–4970, 1980.

    Article  PubMed  CAS  Google Scholar 

  3. Glazer RI, Lloyd LS: Association of cell lethality with incorporation of 5-fluorouracil and 5-fluorouridine into nuclear RNA in human colon carcinoma cells in culture. Mol. Pharmacol. 21: 468–473, 1982.

    PubMed  CAS  Google Scholar 

  4. Wilkinson DS, Pitot HC: Inhibition of ribosomal acid maturation in Novikoff hepatoma cells by 5-fluorouracil and 5-fluorouridine. J. Biol. Chem. 248: 63–68, 1973.

    PubMed  CAS  Google Scholar 

  5. Dolnick BJ, Pink JJ: Effects of 5-fluorouracil on dihydrofolate reductase and dihyrofolate reductase in RNA from methotrexate-resistant KB cells. J. Biol. Chem. 260: 3006–3014, 1985.

    PubMed  CAS  Google Scholar 

  6. Mandel HG, Klubes P, Fernandes DJ: Understanding the actions of carcinostatic drugs to improve chemotherapy: 5-fluorouracil. Adv. Enzyme Regul. 16: 65–77, 1978.

    Article  Google Scholar 

  7. Heidelberger C, Danenberg PV, Moran RG: Fluorinated pyrimidines and their nucleosides. Adv. Enzymol. 4: 58–119, 1983.

    Google Scholar 

  8. Washtien WL: Comparison of 5-fluorouracil metabolism in two human gastrointestinal tumor cell lines. Cancer Res. 44: 909–914, 1984.

    PubMed  CAS  Google Scholar 

  9. Myers CE: The pharmacology of the fluoropyrimidines. Pharmacol. Rev. 33: 1–15, 1981.

    PubMed  CAS  Google Scholar 

  10. Sawyer RC, Stolfi RL, Nayak R, Martin DS: Mechanism of cytotoxicity in 5-fluorouracil chemotherapy of two murine solid tumors. In: Nucleosides and Cancer Treatment, Tattersall MHN, Fox RM (eds), New York, Academic Press, Inc., 1981, pp. 309–338.

    Google Scholar 

  11. Santi DV, McHenry CS, Sommer H: Mechanism of interaction of thymidylate synthetase with 5-fluorodeoxyuridine. Biochemistry 13: 471–481, 1974.

    Article  PubMed  CAS  Google Scholar 

  12. Danenberg PV, Heidelberger C, Mulkins MA, Peterson AR: The incorporation of 5-fluoro-2′-deoxyuridine into DNA of mammalian tumor cells. Biochem. Biophys. Res. Commun. 102: 654–658, 1981.

    Article  PubMed  CAS  Google Scholar 

  13. Cheng YC, Nakayama K: Effects of 5-fluoro-2′-deoxyuridine on DNA metabolism in Hela cells. Mol. Pharmacol. 23: 171–174, 1983.

    PubMed  CAS  Google Scholar 

  14. Major PP, Egan E, Herrick D, Kufe DW: 5-fluorouracil incorporation into DNA of human breast carcinoma cells. Cancer Res. 42: 3005–3009, 1982.

    PubMed  CAS  Google Scholar 

  15. Sawyer RC, Stolfi RL, Martin DS, Spiegelman S: Incorporation of 5-fluorouracil into murine bone marrow DNA in vivo. Cancer Res. 44: 1847–1851, 1984.

    PubMed  CAS  Google Scholar 

  16. Kufe DW, Major PP, Egan EM, Loh E: 5-fluoro-2′-deoxyuridine incorporation of L1210 DNA. J. Biol. Chem. 256: 8885–8888, 1981.

    PubMed  CAS  Google Scholar 

  17. Lonn V, Lonn S: Interaction between 5-fluorouracil and DNA of human colon adenocarcinoma. Cancer Res. 44: 3414–3418, 1984.

    PubMed  CAS  Google Scholar 

  18. Evans RM, Laskin JD, Hakala MT: Assessment of growth limiting events caused by 5-fluorouracil. Cancer Res. 40: 4113–4122, 1980.

    PubMed  CAS  Google Scholar 

  19. Laskin JD, Evans RM, Slocum HK et al: Basis for natural variation in sensitivity to 5-fluorouracil in mouse and human cells in culture. Cancer Res. 39: 383–390, 1979.

    PubMed  CAS  Google Scholar 

  20. Ardalan B, Cooney DA, Jayaram HN et al: Mechanism of sensitivity and resistance of murine tumors to 5-fluorouracil. Cancer Res. 40: 1431–1437, 1980.

    PubMed  CAS  Google Scholar 

  21. Maybaum J, Ullman B, Mandel HG et al: Regulation of RNA-and DNA-directed actions of 5-fluoropyrimidines in mouse T-lymphoma (S-49) cells. Cancer Res. 40: 4209–4215, 1980.

    PubMed  CAS  Google Scholar 

  22. Collins KD, Stark GR: Aspartate transcarbamylase, interaction with the transition state analogue N-(phosphonacetyl)-L-aspartate. J. Biol. Chem. 246: 6599–6605, 1971.

    PubMed  CAS  Google Scholar 

  23. Swyrd EA, Seaver SS, Stark GR: N-(phosphonacetyl)-L-aspartate a potent transition state analog inhibitor of aspartate transcarbamylase, blocks proliferation of mammalian cells in culture. J. Biol. Chem. 249: 6946–6950, 1974.

    Google Scholar 

  24. Ardalan B, Glazer R, Kensler T et al: Biochemical mechanism for the synergism of 5-fluorouracil (5-FU) and phosphonacetyl-L-aspartate (PALA) in human mammary carcinoma cells. Proc. Am. Assoc. Cancer Res. 21: 8, 1980.

    Google Scholar 

  25. Johnson RK, Clement JJ, Howard WS: Treatment of murine tumors with 5-fluorouracil in combination with de novo pyrimidine synthesis inhibitors PALA or pyrazofurin. Proc. Am. Assoc. Cancer Res. 21: 292, 1980.

    Google Scholar 

  26. Kufe DW, Egan EM: Enhancement of 5-fluorouracil incorporation into human lymphoblast ribonucleic acid. Biochem. Pharmacol. 30: 129–133, 1981.

    Article  PubMed  CAS  Google Scholar 

  27. Kufe DW, Major PP: 5-Fluorouracil incorporation into human breast carcinoma RNA correlates with cytoxicity. J. Biol. Chem. 256: 9803–9805, 1981.

    Google Scholar 

  28. Martin DS, Nayak R, Sawyer RC et al: Enhancement of 5-fluorouracil chemotherapy with emphasis on the use of excess thymidine. Cancer Bull. 30: 219–222, 1978.

    Google Scholar 

  29. Martin DS, Stolfi RL, Sawyer RC et al: Biochemical modulation of 5-fluorouracil and cytosine arabinoside with emphasis on thymidine, PALA, and 6-methylmercaptopurine riboside. In: Nucleosides and Cancer Treatment, Tattersal MHN, Fox RM (eds), Australia, Academic Press, 1981, pp. 339–382.

    Google Scholar 

  30. Martin DS, Stolfi RL, Sawyer RC et al: An overview of thymidine. Cancer 45: 1117–1128, 1980.

    Article  PubMed  CAS  Google Scholar 

  31. Bedikian AY, Strochlein JR, Karlin DA et al: Chemotherapy for colorectal cancer with a combination of PALA and 5-FU. Cancer Treat. Rep. 65: 747–753, 1981.

    PubMed  CAS  Google Scholar 

  32. Erlichman C, Donhower RC, Speyer JL et al: Phase I-II trial of N-phosphonacetyl-L-aspartic acid given by intravenous infusion and 5-fluorouracil given by bolus injection. JNCI 68: 227–231, 1982.

    PubMed  CAS  Google Scholar 

  33. Meshad MW, Ervin TJ, Kufe D et al: Phase I trial of combination chemotherapy with PALA and 5-FU. Cancer Treat. Rep. 65: 331–334, 1981.

    PubMed  CAS  Google Scholar 

  34. O’Connell MJ, Powis G, Rubin J, Moertel CG: Pilot study of PALA and 5-FU in patients with advanced cancer. Cancer Treat. Rep. 66: 77–80, 1982.

    PubMed  Google Scholar 

  35. Sartorelli AC, Creasey WA: Combination chemotherapy. In: Cancer Medicine, 2nd edition, Holland JF, Frei, E III (eds), Philadelphia, Lea & Febiger, 1982, pp. 720–730.

    Google Scholar 

  36. Martin DS, Stolfi RL, Sawyer RC: Commentary on clinical predictivity of transplantable tumor systems in the selection of new drugs for solid tumors: Rationale for a three-stage strategy. Cancer Treat. Rep. 68: 1317–1318, 1984.

    PubMed  CAS  Google Scholar 

  37. Martin DS, Stolfi RL, Sawyer RC, Young CW: Application of biochemical modulation with a therapeutically inactive modulating agent in clinical trials of cancer chemotherapy. Cancer Treat. Rep. 69: 421–423, 1985.

    PubMed  CAS  Google Scholar 

  38. Skipper HE, Schabel FM Jr: Quantitative and cytokinetic studies in experimental tumor systems. In: Cancer Medicine, 2nd edition, Holland JF, Frei E III (eds), Philadelphia, Lea & Febiger, 1982, pp. 663–685.

    Google Scholar 

  39. Martin DS, Stolfi RL, Sawyer RC et al: Therapeutic utility of utilizing low doses of N-(phosphonacetyl)-L-aspartic acid in combination with 5-fluorouracil: A murine study with clinical relevance. Cancer Res. 43: 2317–2321, 1983.

    PubMed  CAS  Google Scholar 

  40. Liang CM, Donehower R, Chabner B: Biochemical interactions between N-(phosphonacetyl)-L-aspartate and 5-fluorouracil. Mol. Pharmacol. 21: 224–230, 1982.

    PubMed  CAS  Google Scholar 

  41. Martin DS, Balis ME, Fisher B et al: The role of murine tumor models in cancer treatment research. Cancer Research 46: 2189–2192, 1986.

    PubMed  CAS  Google Scholar 

  42. Casper ES, Vale K, Williams LJ et al: Phase I and clinical pharmacologic evaluation of biochemical modulation of 5-fluorouracil with N-(phosphonacetyl)-L-aspartic acid (PALA). Cancer Res. 43: 2324–2329, 1983.

    PubMed  CAS  Google Scholar 

  43. Loo TL, Friedman J, Moore EC et al: Pharmacological disposition of N-(phosphonacetyl)-L-aspartate in humans. Cancer Res. 40: 86–90, 1980.

    PubMed  CAS  Google Scholar 

  44. Moore EC, Friedman J, Valdivieso M et al: Aspartate carbamyltransferase activity, drug concentrations, and pyrimidine nucleotides in patients tissue after treatment with N-(phosphonacetyl)-L-aspartate (PALA). Biochem. Pharmacol. 31: 3317–3321, 1982.

    Article  PubMed  CAS  Google Scholar 

  45. Valdivieso M, Moore EC, Burgess AM et al: Phase I clinical study of N-(phosphonacetyl)-L-aspartic acid (PALA). Cancer Treat. Rep. 64: 285–292, 1980.

    PubMed  CAS  Google Scholar 

  46. Kensler TW, Mutter G, Hankerson JG et al: Mechanism of resistance of variants of the Lewis lung carcinoma to N(phosphonacetyl)-L-aspartic acid. Cancer Res. 41: 894–904, 1981.

    PubMed  CAS  Google Scholar 

  47. Kufe DW, Major PP, Egan EM, Beardsley GP: Correlation of cytotoxicity with incorporation of ara-C into DNA. J. Biol. Chem. 255: 8997–9000, 1980.

    PubMed  CAS  Google Scholar 

  48. Momparler RL, Chu MY, Fischer GA: Studies on a new mechanism of resistance of L51784 murine leukemia cells to cytosine arabinoside. Biochem. Biophys. Acta. 161: 481–493, 1968.

    PubMed  CAS  Google Scholar 

  49. Tattersall MHN, Ganeshagaru K, Heffbrand AV: Mechanisms of resistance of human acute leukemia cells to cytosine arabinoside. Br. J. Haematol. 27: 39–46, 1974.

    Article  PubMed  CAS  Google Scholar 

  50. Jayaram HN, Cooney DA, Ryan JA et al: L-(αS, 5S)-α-amino-3-chloro-4, 5-dihydro-5-isoxazoleacetic acid (NSC-163501): A new amino acid antibiotic with the properties of an antagonist of L-glutamine. Cancer Treat. Rep. 59: 481–491, 1975.

    Google Scholar 

  51. Aoki T, Sebolt J, Weber G: In vivo inactivation of carbamoylphosphate synthetase II in rat hepatoma by Acivicin. Biochem. Pharmacol. 31: 927–932, 1982.

    Article  PubMed  CAS  Google Scholar 

  52. Kensler TW, Jayaram HN, Cooney DA: Effects of Acivicin and PALA, singly and in combination, on de novo pyrimidine biosynthesis. Adv. Enzyme Regul. 20: 57–73, 1982.

    Article  PubMed  CAS  Google Scholar 

  53. Loh E, Kufe DW: Synergistic effects with inhibitors of de novo pyrimidine synthesis, Acivicin and N-(phosphonacetyl)L-aspartic acid. Cancer Res. 41: 3419–3423, 1981.

    PubMed  CAS  Google Scholar 

  54. Stolfi RL, Sawyer RC, Martin DS: Combination chemotherapy with Acivicin, N-(phosphonacetyl)-L-aspartic acid (PALA) and ara-C against CD8F1 breast tumor. Proc. Am. Assoc. Cancer Res. 26: 241, 1985.

    Google Scholar 

  55. Momparler RL, Brent TP, Labitan A, Krygier V: Studies on the phosphorylation of cytosine arabinoside in mammalian cells. Mol. Pharmacol. 7: 413–419, 1971.

    PubMed  CAS  Google Scholar 

  56. Jackson RC: The regulation of thymidylate biosynthesis in Novikoff hepatoma cells and the effects of amethopterin, 5-fluorodeoxyuridine, and 3-deazauridine. J. Biol. Chem. 253: 7440–7446, 1978.

    PubMed  CAS  Google Scholar 

  57. Plagemann PG, Mary R, Wohlhueter RM: Transport and metabolism of deoxycytidine and 1-B-D-arabinofuranosylcytosine into cultured Novikoff rat hepatoma cells. Relationship to phosphorylation and regulation of triphosphate synthesis. Cancer Res. 38: 978–989, 1978.

    CAS  Google Scholar 

  58. Ives DH, Durham IP: Deoxycytidine kinase III. Kinetic and allosteric regulation of the calf thymus enzyme. J. Biol. Chem. 245: 2285–2294, 1970.

    CAS  Google Scholar 

  59. Harris AW, Reynolds EC, Finch LR: Effect of thymidine on the sensitivity of cultured mouse tumor cells to 1-B-D-arabinofuranosylcytosine. Cancer Res. 39: 538–541, 1979.

    PubMed  CAS  Google Scholar 

  60. Kinahan JJ, Kowal EP, Grindey GB: Biochemical and anti-tumor effects of the combination of thymidine and 1-B-D-arabinosylcytosine against leukemia L1210. Cancer Res. 41: 445–451, 1981.

    PubMed  CAS  Google Scholar 

  61. Cohen A, Ullman B: Analysis of the drug synergism between thymidine and arabinosyl cytosine using mouse S49 T lymphoma mutants. Cancer Chemother. Pharmacol. 14: 70–73, 1985.

    Article  PubMed  CAS  Google Scholar 

  62. Grant S, Lehman C, Cadman E: Enhancement of 1-B-D-arabinofuranosylcytosine accumulation within L1210 cells and increased cytotoxicity following thymidine exposure. Cancer Res. 40: 1525–1531, 1980.

    PubMed  CAS  Google Scholar 

  63. Breitman JR, Keene BR: Synergistic cytotoxicity to melanoma and leukemias in vitro with thymidine (NSC-21548) and arabinofuranosylcytosine (NSC-63878). Proc. Am. Assoc. Cancer Res. 20: 89, 1979.

    Google Scholar 

  64. Danhauser LL, Rustum YM: Potential for selective enhancement of the in vivo metabolism of 1-B-D-arabinofuranosylcytosine in rats by thymidine pretreatment. Cancer Res. 45: 2002–2007, 1985.

    PubMed  CAS  Google Scholar 

  65. Grant S, Rauscher F, Cadman E: Differential effect of N-(phosphonacetyl)-L-aspartate on 1-B-D-arabinofuranosylcytosine metabolism and cytotoxicity in human leukemia and normal bone marrow progenitors. Cancer Res. 42: 4007–4013, 1982.

    PubMed  CAS  Google Scholar 

  66. Chabner B: Cytosine arabinoside. In: Pharmacology of Anticancer Agents, Chabner B (ed), Philadelphia, W.B. Saunders Co., 1982, pp. 387–396.

    Google Scholar 

  67. Houghton JA, Houghton PJ, Wooten RS: Mechanism of induction of gastrointestional toxicity, in the mouse by 5-fluor-ouracil, 5-fluorouridine, and 5-fluro-2′-deoxyuridinc. Cancer Res. 39: 2406–2413, 1979.

    PubMed  CAS  Google Scholar 

  68. Martin DS, Stolfi RL, Sawyer RC et al: High-dose 5-fluor-ouracil with delayed uridine “rescue” in mice. Cancer Res. 42: 3964–3970, 1982.

    PubMed  CAS  Google Scholar 

  69. Klubes P, Cerna I, Meldon M: Uridine rescue from the lethal toxicity of 5-fluorouracil in mice. Cancer Chemother. Pharmacol. 8: 17–21, 1982.

    Article  PubMed  CAS  Google Scholar 

  70. Klubes P, Cerna I: Use of uridine rescue to enhance the antitumor selectivity of 5-fluorouracil. Cancer Res. 43: 3182–3186, 1983.

    PubMed  CAS  Google Scholar 

  71. Martin DS, Stolfi RL, Sawyer RC et al: Improved therapeutic index with sequential N-phosphonacetyl-L-aspartate plus high-dose methotrexate plus high-dose 5-fluorouracil and appropriate rescue. Cancer Res. 43: 4653–4661, 1983.

    PubMed  CAS  Google Scholar 

  72. Sawyer RC, Stolfi RL, Spiegelman S, Martin DS: Effect of uridine on the metabolism of 5-fluorouracil in the CD8F1 murine mammary carcinoma system. Pharmaceutical Res. 2: 69–75, 1984.

    Article  Google Scholar 

  73. Benz C, Cadman E: Modulation of 5-fluorouracil metabolism and cytotoxicity by antimetabolite pretreatment in human colorectal adenocarcinoma HCT-8. Cancer Res. 41: 994–999, 1981.

    PubMed  CAS  Google Scholar 

  74. Cadman E, Benz C, Heimer R, O’Shaughnessy J: Effects of de novo purine synthesis inhibitors on 5-fluorouracil metabolism and cytotoxicity. Biochem. Pharmacol. 30: 2469–2472, 1981.

    Article  PubMed  CAS  Google Scholar 

  75. Glazer R, Lloyd L: Association of cell lethality with incorporation of 5-fluorouracil and 5-fluorouridine into nuclear RNA in human colon carcinoma cells in culture. Mol. Pharmacol. 21: 468–473, 1982.

    PubMed  CAS  Google Scholar 

  76. Martin DS, Stolfi RL: Unpublished data.

    Google Scholar 

  77. Belousova AK, Gerasimona GK: Search for the biochemical parameters of tumor cell sensitivity and resistance to antimetabolites. Antibiot. Chemother. 28: 48–52, 1980.

    PubMed  CAS  Google Scholar 

  78. Umeda M, Heidelberger C: Fluorinated pyrimidines. XXX. Comparative studies of fluorinated pyrimidines with various cell lines. Cancer Res. 28: 2529–2538, 1968.

    CAS  Google Scholar 

  79. Ahmed NK, Haggit RC, Welch AD: Enzymes of salvage and de novo pathways of synthesis of pyrimidine nucleotides in human colorectal adenocarcinomas. Biochem. Pharmacol. 31: 2485–2488, 1982.

    Article  PubMed  CAS  Google Scholar 

  80. Leyva A, van Groeningen CJ, Kraal I et al: Phase I and pharmacokinetic studies of high-dose uridine intended for rescue from 5-fluorouracil toxicity. Cancer Res. 44: 5928–5933, 1984.

    PubMed  CAS  Google Scholar 

  81. van Groeningen CJ, Leyva A, Kraal I et al: Clinical and pharmacokinetic studies of prolonged administration of high-dose uridine intended for rescue from 5-fluorouracil toxicity. Cancer Treat. Rep., submitted for publication.

    Google Scholar 

  82. Karle JM, Anderson LW, Dietrick DD, Cysk RL: Effect of inhibitors of the de novo pyrimidine biosynthetic pathway on serum uridine levels in mice. Cancer Res. 41: 4952–4955, 1981.

    PubMed  CAS  Google Scholar 

  83. Gasser T, Moyer JD, Handschumacher RE: Novel single pass exchange of circulating uridine in rat liver. Sci. 213: 777–778, 1981.

    Article  CAS  Google Scholar 

  84. Moyer JD, Oliver JT, Handschumacher RE: Salvage of circulating pyrimidine nucleosides in the rat. Cancer Res. 41: 3010–3017, 1981.

    PubMed  CAS  Google Scholar 

  85. Niedzwicki JG, Chu SH, el Kouni MH et al: 5-Benzylacyclouridine and 5-benzyloxybenzylacyclouridine, potent inhibitors of uridine phosphorylase. Biochem. Pharmacol. 31: 1857–1861, 1982.

    Article  PubMed  CAS  Google Scholar 

  86. Niedzwicki JG, el Kouni MH, Chu SH, Cha S: Pyrimidine acyclonucleosides, inhibitors of uridine phosphorylase. Biochem. Pharmacol. 30: 2097–2101, 1981.

    Article  PubMed  CAS  Google Scholar 

  87. Chu MYW, Naguib FNM, Iltzsch MH et al: Potentiation of 5-fluoro-2′-deoxyuridine antineoplastic activity by the uridine phosphorylase inhibitors benzylacyclouridine and benzyloxybenzylacyclouridine. Cancer Res. 44: 1852–1856, 1984.

    PubMed  CAS  Google Scholar 

  88. Darnowski JW, Handschumacher RE: Pharmacokinetics of benzyluridine (BAU) and its utility as a potential rescuing agent from 5-fluorouracil (FUra) induced toxicity. Proc. Am. Assoc. Cancer Res. 25: 358, 1984.

    Google Scholar 

  89. Darnowski JW, Handschumacher RE: Tissue specific enhancement of uridine utilization and 5-fluorouracil therapy by benzylacyclouridine. Cancer Res. 45: 5364–5368, 1985.

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. Daniel S. Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Wayne State University School of Medicine, Detroit, Michigan, USA

    Frederick A. Valeriote  & Laurence H. Baker  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1986 Martinus Nijhoff Publishing, Boston

About this chapter

Cite this chapter

Martin, D.S. (1986). Biochemical Modulation of Pyrimidine Pools for Enhancement of Antipyrimidine Cytotoxicity. In: Valeriote, F.A., Baker, L.H. (eds) Biochemical Modulation of Anticancer Agents: Experimental and Clinical Approaches. Developments in Oncology, vol 47. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-2331-0_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-4613-2331-0_4

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4612-9432-0

  • Online ISBN: 978-1-4613-2331-0

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation