Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1980 May;41(5):816–820. doi: 10.1038/bjc.1980.146

The effect of methotrexate on folate metabolism in the rat.

P A Barford, J A Blair, M A Malghani
PMCID: PMC2010325  PMID: 7426306

Abstract

The metabolism of 2-[14C]-folic acid, 2-[14C]-5-methyltetrahydrofolate 5-[14C]-methyltetrahydrofolate, and a mixture of 2-[14C]-folic acid and 3',5',7,9-[3H]-folic acid has been studied in rats that were dosed with methotrexate (MTX) 24 h before receiving the radioactive folate. Methotrexate increases urinary excretion of radioactivity in rats given 2-[14C]-folic acid, but there was no significant increase in urinary radioactivity in animals given 5-methyltetrahydrofolate. Animals dosed with MTX had less of the dose in the liver, and excreted more of the dose via the faeces. These results are consistent with the known biochemical effects of methotrexate. Experiments with a mixture of 2-[14C]-folic acid and 3',5',7,9-[3H]-folic acid indicate that there is an increase in scission of the folate molecule following a dose of MTX.

Full text

PDF
816

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BERTINO J. R., PERKINS J. P., JOHNS D. G. PURIFICATION AND PROPERTIES OF DIHYDROFOLATE REDUCTASE FROM EHRLICH ASCITES CARCINOMA CELLS. Biochemistry. 1965 May;4:839–846. doi: 10.1021/bi00881a007. [DOI] [PubMed] [Google Scholar]
  2. Barford P. A., Blair J. A. Effect of an implanted Walker tumour on metabolism of folic acid in the rat. Br J Cancer. 1978 Jul;38(1):122–129. doi: 10.1038/bjc.1978.171. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Barford P. A., Blair J. A., Malghani M. A. The effect of methotrexate on the metabolism of [14C]folates in the rat. Biochem Soc Trans. 1976;4(5):912–914. doi: 10.1042/bst0040912. [DOI] [PubMed] [Google Scholar]
  4. Barford P. A., Staff F. J., Blair J. A. The metabolic fate of (2-14C)folic acid and a mixture of (2-14C)- and (3',5',9-3h)-folic acid in the rat. Biochem J. 1978 Aug 15;174(2):579–583. doi: 10.1042/bj1740579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Barford P. A., Staff R. J., Blair J. A. Retained folates in the rat. Biochem J. 1977 Jun 15;164(3):601–605. doi: 10.1042/bj1640601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chabner B. A., Myers C. E., Coleman C. N., Johns D. G. The clinical pharmacology of antineoplastic agents (first of two parts). N Engl J Med. 1975 May 22;292(21):1107–1113. doi: 10.1056/NEJM197505222922107. [DOI] [PubMed] [Google Scholar]
  7. Connor M. J., Pheasant A. E., Blair J. A. The identification of p-acetamidobenzoate as a folate degradation product in rat urine. Biochem J. 1979 Mar 15;178(3):795–797. doi: 10.1042/bj1780795. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Goldman I. D. Effects of methotrexate on cellular metabolism: some critical elements in the drug-cell interaction. Cancer Treat Rep. 1977 Jul;61(4):549–558. [PubMed] [Google Scholar]
  9. Henderson E. S., Adamson R. H., Denham C., Oliverio V. T. The metabolic fate of tritiated methotrexate. I. Absorption, excretion, and distribution in mice, rats, dogs and monkeys. Cancer Res. 1965 Aug;25(7):1008–1017. [PubMed] [Google Scholar]
  10. Henderson E. S., Adamson R. H., Oliverio V. T. The metabolic fate of tritiated methotrexate. II. Absorption and excretion in man. Cancer Res. 1965 Aug;25(7):1018–1024. [PubMed] [Google Scholar]
  11. Lavoie A., Tripp E., Hoffbrand A. V. The effect of vitamin B12 deficiency on methylfolate metabolism and pteroylpolyglutamate synthesis in human cells. Clin Sci Mol Med. 1974 Dec;47(6):617–630. doi: 10.1042/cs0470617. [DOI] [PubMed] [Google Scholar]
  12. Lei F. H., Lucas M. L., Blair J. A. The influence of pH, low sodium ion concentration and methotrexate on the jejunal-surface pH: a model for folic acid transfer. Biochem Soc Trans. 1977;5(1):149–152. doi: 10.1042/bst0050149. [DOI] [PubMed] [Google Scholar]
  13. Lucas M. L., Swanston S. K., Lei F. H., Mangkornthong P., Blair J. A. Effect of ethanol, diphenylhydantoin, methotrexate and low sodium ion concentration on jejunal surface pH and folic acid transfer in the rat [proceedings]. Biochem Soc Trans. 1978;6(1):297–299. doi: 10.1042/bst0060297. [DOI] [PubMed] [Google Scholar]
  14. McBurney M. W., Whitmore G. F. Isolation and biochemical characterization of folate deficient mutants of Chinese hamster cells. Cell. 1974 Jul;2(3):173–182. doi: 10.1016/0092-8674(74)90091-9. [DOI] [PubMed] [Google Scholar]
  15. Pollock R. J., Kaufman S. Dihydropteridine reductase may function in tetrahydrofolate metabolism. J Neurochem. 1978 Jul;31(1):115–123. doi: 10.1111/j.1471-4159.1978.tb12439.x. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES