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. 1982 Jun;45(6):843–850. doi: 10.1038/bjc.1982.136

N-methylformamide: antitumour activity and metabolism in mice.

A Gescher, N W Gibson, J A Hickman, S P Langdon, D Ross, G Atassi
PMCID: PMC2011036  PMID: 7201320

Abstract

The antitumour activities of N-methylformamide, N-ethylformamide and formamide against a number of murine tumours in vivo (Sarcoma 180, M5076 ovarian sarcoma and TLX5 lymphoma) have been estimated. In all cases N-methyl-formamide had significant activity, formamide had marginal or no activity and N-ethylformamide had no significant activity. N-methylformamide and N-ethylformamide were equitoxic to the TLX5 lymphoma in vitro. Formamide was found as a metabolite in the plasma and urine of animals given N-methylformamide and N-ethylformamide, but excretion profiles do not support the hypothesis that formamide is an active antitumour species formed from N-alkylformamides. No appreciable metabolism of N-methylformamide occurred under a variety of conditions with liver preparations in vitro. N-methylformamide, but not N-ethylformamide or formamide, reduced liver soluble non-protein thiols by 59.8% 1 h after administration of an effective antitumour dose.

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Selected References

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

  1. BARCLAY R. K., GARFINKEL E., STOCK C. C. The influence of N-methylformamide on C14-formate incorporation. I. In nucleic acids of rat liver. J Biol Chem. 1954 Jun;208(2):875–882. [PubMed] [Google Scholar]
  2. BURCHENAL J. H., KARNOFSKY D. A., MYERS W. P. L. The hepatotoxic action of N-methylformamide in man. Cancer. 1956 Sep-Oct;9(5):949–954. doi: 10.1002/1097-0142(195609/10)9:5<949::aid-cncr2820090514>3.0.co;2-k. [DOI] [PubMed] [Google Scholar]
  3. Barnes J. R., Ranta K. E. The metabolism of dimethylformamide and dimethylacetamide. Toxicol Appl Pharmacol. 1972 Oct;23(2):271–276. doi: 10.1016/0041-008x(72)90190-1. [DOI] [PubMed] [Google Scholar]
  4. CLARKE D. A., PHILIPS F. S., STERNBERG S. S., BARCLAY R. K., STOCK C. C. Effects of N-methylformamide and related compounds in mouse sarcoma 180. Proc Soc Exp Biol Med. 1953 Oct;84(1):203–207. doi: 10.3181/00379727-84-20590. [DOI] [PubMed] [Google Scholar]
  5. COOK L., MACKO E., FELLOWS E. J. The effect of beta-diethylaminoethyldiphenyl-propylacetate hydrochloride on the action of a series of barbiturates and C.N.S. depressants. J Pharmacol Exp Ther. 1954 Nov;112(3):382–386. [PubMed] [Google Scholar]
  6. Connors T. A., Hare J. R. Studies of the mechanism of action of the tumour-inhibitory nitrosoureas. Biochem Pharmacol. 1975 Dec 1;24(23):2133–2140. doi: 10.1016/0006-2952(75)90042-8. [DOI] [PubMed] [Google Scholar]
  7. EIDINOFF M. L., KNOLL J. E., MARANO B. J., KLEIN D. Pyrimidine studies. III. Effect of several compounds with antitumor activity on utilization of precursors for synthesis of nucleic acid pyrimidines. Cancer Res. 1961 Nov;21:1377–1385. [PubMed] [Google Scholar]
  8. ELLMAN G. L. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959 May;82(1):70–77. doi: 10.1016/0003-9861(59)90090-6. [DOI] [PubMed] [Google Scholar]
  9. FURST A., CUTTING W. C., GROSS H. Retardation of growth of Ehrlich ascites tumor by formamides and related compounds. Cancer Res. 1955 Jun;15(5):294–299. [PubMed] [Google Scholar]
  10. Gescher A., Hickman J. A., Simmonds R. J., Stevens M. F., Vaughan K. Studies of the mode of action of antitumour triazenes and triazines-II. Investigation of the selective toxicity of 1-aryl-3,3-dimethyltriazenes. Biochem Pharmacol. 1981 Jan 1;30(1):89–93. doi: 10.1016/0006-2952(81)90288-4. [DOI] [PubMed] [Google Scholar]
  11. Gescher A., Hickman J. A., Stevens M. F. Oxidative metabolism of some N-methyl containing xenobiotics can lead to stable progenitors of formaldehyde. Biochem Pharmacol. 1979 Nov 1;28(21):3235–3238. doi: 10.1016/0006-2952(79)90069-8. [DOI] [PubMed] [Google Scholar]
  12. Gescher A., Raymont C. Studies of the metabolism of N-methyl containing anti-tumour agents: 14CO2 breath analysis after administration of 14C-labelled N-methyl drugs, formaldehyde and formate in mice. Biochem Pharmacol. 1981 Jun 1;30(11):1245–1252. doi: 10.1016/0006-2952(81)90305-1. [DOI] [PubMed] [Google Scholar]
  13. Higashi T., Tateishi N., Naruse A., Sakamoto Y. A novel physiological role of liver glutathione as a reservoir of L-cysteine. J Biochem. 1977 Jul;82(1):117–124. doi: 10.1093/oxfordjournals.jbchem.a131659. [DOI] [PubMed] [Google Scholar]
  14. NASH T. The colorimetric estimation of formaldehyde by means of the Hantzsch reaction. Biochem J. 1953 Oct;55(3):416–421. doi: 10.1042/bj0550416. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. SARTORELLI A. C., LePAGE G. A. The development and biochemical characterization of resistance to azaserine in a TA 3 ascites carcinoma. Cancer Res. 1958 May;18(4):457–463. [PubMed] [Google Scholar]
  16. SKIPPER H. E., SCHABEL F. M., Jr, BINNS V., THOMSON J. R., WHEELER G. P. Studies on the mechanism of action and anticancer activity of N-methylformamide. Cancer Res. 1955 Mar;15(3):143–146. [PubMed] [Google Scholar]
  17. Talmadge J. E., Key M. E., Hart I. R. Characterization of a murine ovarian reticulum cell sarcoma of histiocytic origin. Cancer Res. 1981 Apr;41(4):1271–1280. [PubMed] [Google Scholar]
  18. WHEELER G. P., GRAMMER M. G. Prevention of the inhibitory effects of urethan, formamide, and N-methylformamide on the growth of Escherichia coli. Biochem Pharmacol. 1960 Jul;3:316–327. doi: 10.1016/0006-2952(60)90097-6. [DOI] [PubMed] [Google Scholar]

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