The anti-cancer drug 5-fluorouracil is metabolized by the isolated perfused rat liver and in rats into highly toxic fluoroacetate

British Journal of Cancer

Volumn 77, Issue 1, 1998, Pages 79-86

  Arellano, M ^a   Malet Martino, M ^a   Martino, R ^a   Gires, P ^b  

^a UMR 5623 CNRS UPS)   (France)

^b SANOFI   (France)

Author keywords

5 fluorouracil; 19F nuclear magnetic resonance; Fluoroacetate; Isolated perfused rat liver; Metabolism; Rat urine; fluoro alanine; fluoro hydroxypropionic acid

Indexed keywords

ALPHA FLUORO BETA ALANINE; ANTINEOPLASTIC AGENT; DRUG METABOLITE; FLUOROACETIC ACID; FLUOROURACIL;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; DRUG METABOLISM; DRUG TRANSFORMATION; ISOLATED LIVER; LIVER METABOLISM; MALE; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PRIORITY JOURNAL; RAT; URINE;

EID: 6844251612     PISSN: 00070920     EISSN: None     Source Type: Journal    
DOI: 10.1038/bjc.1998.12     Document Type: Article

References (43)

1. Anand AJ (1994) Fluorouracil cardiotoxicity. Ann Pharmacother 28: 374-378
2. Arellano M, Malet-Martino M, Martino R and Spector T (1997) 5-Ethynyluracil (GW776): effects on the formation of the toxic catabolites of 5-fluorouracil, fluoroacetate and fluorohydroxy-propionic acid, in the isolated perfused rat liver model. Br J Cancel 76: 1170-1180
3. Baccanari DP, Davis ST, Knick VC and Spector T (1993) 5-Ethynyluracil (776C85): a potent modulator of the pharmacokinetics and antitumor efficacy of 5-fluorouracil. Proc Natl Acad Sci USA 90: 11064-11068
4. Bosakowski T and Levin AA (1986) Serum citrate as a peripheral indicator of fluoroacetate and fluorocitrate toxicity in rats and dogs. Toxicol Appl Pharmacol 85: 428-436
5. Burke DG, Lew DKT and Cominos X (1989) Determination of fluoroacetate in biological matrixes as the dodecyl ester. J Assoc Off Annal Chem 12: 503-507
6. De Forni M, Malet-Martino MC, Jaillais P, Shubinski RE, Bachaud JM, Lemaire L, Canal P, Chevreau C, Carrié D, Soulié P, Roché H, Boudjema B, Mihura J, Martino R, Bernadet P and Bugat (1992) Cardiotoxicity of high-dose continuous infusion fluorouracil: a prospective clinical study. J Clin Oncol 10: 1795-1801
7. De Vita VT, Hellman S and Rosenberg SA (1993) Cancer Principles and Practice of Oncology. Lippincott: Philadelphia
8. Gamelin E, Gamelin L, Larra F, Turcant A, Alain P, Maillart P, Allain YM, Minier JF and Dubin J (1991) Toxicité cardiaque aigüe du 5-fluorouracile: corrélation pharmacocinétique. Bull Cancer 78: 1147-1153
9. Gani D, Hitchcock PB and Young DW (1985) Stereochemistry of catabolism of the DNA base thymine and of the anti-cancer drug 5-fluorouracil. J Chem Soc Perkin Trans 1: 1363-1372
10. Griffith OW (1986) β-amino acids: mammalian metabolism and utility as α-amino acid analogues. Ann Rev Biochem 55: 855-878
11. 19F nuclear magnetic resonance spectroscopy, for patients receiving chemotherapy with or without methotrexate pretreatment. Cancer Res 48: 1680-1688
12. 14F NMR spectroscopy. Magn Reson Med 36: 445-450
13. Kaneko M, Kontani Y, Kikugawa M and Tamaki N (1992) Inhibition of D-3-aminoisobutyrate-pyruvate aminotransferase by 5-fluorouracil and α-fluoro-β-alanine. Biochim Biophys Acta 1122: 45-49
14. Keller DA, Roe DC and Lieder PH (1996) Fluoroacetate-mediated toxicity of flourinated ethanes. Fundament Appl Toxicol 30: 213-219
15. Koenig H and Patel A (1970) Biochemical basis for fluorouracil neurotoxicity. Arch Neurol 23: 155-160
16. Kramer HL (1984) Liquid chromatographic determination of sodium fluoroacetate (compound 1080) in meat baits and formulations. J Assoc Off Anal Chem 67: 1058-1061
17. Lemaire L, Malet-Martino MC, De Forni M, Martino R and Lasserre B (1992) Cardiotoxicity of commercial 5-fluorouracil vials stems from the alkaline hydrolysis of this drug. Br J Cancer 66: 119-127
18. Lemaire L, Malet-Martino MC, Martino R, De Forni M and Lasserre B (1994) The Tris formulation of 5-fluorouracil is more cardiotoxic than the sodium salt formulations. Oncol Rep 1: 173-174
19. Lemaire L, Arellano M, Malet-Martino M and Martino R (1996) A metabolite of 5-fluorouracil in humans: 2-fluoro-3-hydroxypropionic acid. Proc Am Assoc Cancer Res 37: 1225
20. Lozeron H, Gordon M, Gabriel T, Tautz W and Duchinsky R (1964) The photochemistry of 5-fluorouracil. Biochemistry 3: 1844-1850
21. Malet-Martino MC and Martino R (1992) Magnetic resonance spectroscopy: a powerful tool for drug metabolism studies. Biochimie 74: 785-800
22. Martino R, Lopez A, Malet-Martino MC, Bernadou J and Armand JP (1985) Release of fluoride ion from 5′-deoxy-5-fluorouridine, an antineoplastic fluoropyrimidine, in humans. Drug Metab Dispos 13: 116-118
23. 151F NMR analysis of the carbamate reaction of α-fluoro-β-alanine, the major catabolite of fluoropyrimidines. Application to FBAI. carbamate determination in body fluids of patients treated with 5′-deoxy-5-fluorouridine. Drug Metab Dispos 15: 897-904
24. Meldrum GK and Bignell JT (1957) The use of sodium fluoroacetate (compound 1080) for the control of the rabbit in Tasmania. Aust Veter J 33: 186-196
25. Moertel CG, Reitemeier RJ, Bolton CF and Shorter RG (1964) Cerebellar ataxia associated with fluorinated pyrimidine therapy. Cancer Chemother Rep 41: 15-18
26. Moore DH, Fowler WC and Crumpler LS (1990) 5-fluorouracil neurotoxicity. Gynecol. Oncol. 36: 152-154
27. Mori M, Nakajima H and Seto Y (1996) Determination of fluoroacetate in aqueous samples by headspace gas chromatography. J Chromatogr A 736: 229-234
28. +4. J Biol Chem 235: 433-437
29. Okeda R, Shibutani M, Mutsuo T, Kuroiwa T, Shimokawa R, and Tajima T (1990) Experimental neurotoxicity of 5-fluorouracil and its derivatives is due to poisoning by the monofluorinated organic metabolites, monofluoroacetic acid and α-fluoro-β-alanine. Acta Neuropathol 81: 66-73
30. Okuno I, Meeker DL and Felton RR (1982) Modified gas liquid chromatographic method for determination of compound 1080 (sodium fluoroacetate). J Assoc Off Anal Chem 65: 1102-1105
31. Ozawa H and Tsukioka T (1987) Gas chromatographic determination of sodium immofluoroacetate in water by derivatization with dicylohexylcarbodiimide. Anal Chem 59: 2914-2417
32. Pattison FLM and Peters RA (1966) Monofluoro aliphatic compounds. In Handbook of Experimental Pharmacology, Smith FA. (ed), pp. 387-458. Springer: New York
33. 4-labeled-β-alanine in the intact rat. J Biol Chem 215: 345-351
34. Porter DJT, Harrington JA, Almond MR, Chestnut WG, Tanoury G and Spector T (1995) Enzymatic elimination of fluoride from α-fluoro-β-alanine. Biochem Pharmacol 50: 1475-1484
35. Ray AC, Post LO and Reagor JC (1981) High pressure liquid chromatographic determination of sodium fluoroacetate (compound 1080) in canine gastric content J Assoc Off Anal Chem 64: 19-24
36. Rezkalla S, Kloner RA, Ensley J, Al-Sarraf M, Revels S, Olivenstein A, Bhasin S, Kerpel-Fronious S and Turi ZG (1989) Continuous ambulatory ECG monitoring during fluorouracil therapy: a prospective study. J Clin Oncol 7: 509-514
37. Robben NC, Pippas AW and Moore JO (1993) The syndrome of 5-fluorouracil cardiotoxicity. An elusive cardiopathy. Cancer 71: 493-509
38. 4PteGlu-catalyzed release of fluoride ion from α-fluoro-β-alanine. In Chemistry and Biology of Pteridines. 1989 Proc Int Symp Pteridines Folic Acid Deriv. Curtius HC, Ghisla S and Blau N. (eds), Vol 9, pp. 811-816. Walter de Gruyter: Berlin
39. Tamaki N, Kaneko M, Mizota C, Kikugawa M and Fujimoto S (1990) Purification. characterization and inhibition of D-3-aminoisobutyrate aminotransferase from the rat liver. Eur J Biochem 189: 39-45
40. Walsh C (1983) Fluorinated substrate analogs: routes of metabolism and selective toxicity. Adv Enzymol 55: 197-289
41. Wong DH, Kinnear JE and Runham CF (1995) A simple rapid bioassay for compound 1080 (sodium fluoroacetate) in bait materials and soil its technique and applications. Wildlife Res 22: 561-568
42. Yonaha K, Suzuki K and Toyama S (1985) Streptomyces β-alanine:α-ketoglutarate aminotransferase, a novel ω-amino acid transaminase. J Biol Chem 260: 3265-3268
43. Zhang R, Soong SJ, Liu T, Barnes E and Diasio RB (1992) Pharmacokinetics and tissue distribution of 2-fluoro-β-alanine in rats. Potential relevance to toxicity pattern of 5-fluorouracil. Drug Metab Dispos 20: 113-119