Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1980 Apr;41(4):630–635. doi: 10.1038/bjc.1980.106

Time dependence of the in vitro cytotoxicity of hexamethylmelamine and its metabolites.

M D'Incalci, E Erba, G Balconi, L Morasca, S Garattini
PMCID: PMC2010283  PMID: 6770884

Abstract

The cytotoxicity of hexamethylmelamine (HMM) and its metabolites pentamethylmelamine (PMM), N,2,2,4,6-tetramethylmelamine (TMM) and hydroxymethylpentamethylmelamine (HMPMM) and of the alkylating agent triethylenemelamine (TEM) were studied on a cell line derived from a human ovarian cancer, by measuring [3H]TdR uptake. After 24 h of incubation all the tested compounds inhibited [3H]TdR uptake, but only at a concentration of 100 micrograms/ml. However, after 120 h incubation, concentrations of 0.1--10 micrograms/ml resulted in highly significant cytotoxicity. HMPMM and TEM were the most active and their effect was not reversed 72 h after their removal. In our in vitro system no metabolism of HMM was observed.

Full text

PDF
630

Selected References

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

  1. Blum R. H., Livingston R. B., Carter S. K. Hexamethylmelamine--a new drug with activity in solid tumors. Eur J Cancer. 1973 Mar;9(3):195–202. doi: 10.1016/s0014-2964(73)80019-2. [DOI] [PubMed] [Google Scholar]
  2. Bolis G., D'Incalci M., Belloni C., Mangioni C. Hexamethylmelamine in ovarian cancer resistant to cyclophosphamide and adriamycin. Cancer Treat Rep. 1979 Aug;63(8):1375–1377. [PubMed] [Google Scholar]
  3. Bonomi P. D., Mladineo J., Morrin B., Wilbanks G., Jr, Slayton R. E. Phase II trial of hexamethylmelamine in ovarian carcinoma resistant to alkylating agents. Cancer Treat Rep. 1979 Jan;63(1):137–138. [PubMed] [Google Scholar]
  4. Bryan G. T., Worzalla J. F., Gorske A. L., Ramirez G. Plasma levels and urinary excretion of hexamethylmelamine following oral administration to human subjects with cancer. Clin Pharmacol Ther. 1968 Nov-Dec;9(6):777–782. doi: 10.1002/cpt196896777. [DOI] [PubMed] [Google Scholar]
  5. D'Incalci M., Bolis G., Mangioni C., Morasca L., Garattini S. Variable oral absorption of hexamethylmelamine in man. Cancer Treat Rep. 1978 Dec;62(12):2117–2119. [PubMed] [Google Scholar]
  6. D'Incalci M., Morazzoni P., Pantarotto C. Gas chromatographic determination of hexamethylmelamine in mouse plasma. Anal Biochem. 1979 Nov 1;99(2):441–449. doi: 10.1016/s0003-2697(79)80030-5. [DOI] [PubMed] [Google Scholar]
  7. DeMilo A. B., Borkovec A. B. Insect chemosterilants. VII. Oxidative degradation of hexamethylmelamine. J Med Chem. 1968 Sep;11(5):961–963. doi: 10.1021/jm00311a009. [DOI] [PubMed] [Google Scholar]
  8. Gescher A., D'Incalci M., Fanelli R., Farina P. N-Hydroxymethylpentamethylmelamine, a major in vitro metabolite of hexamethylmelamine. Life Sci. 1980 Jan 14;26(2):147–154. doi: 10.1016/0024-3205(80)90059-4. [DOI] [PubMed] [Google Scholar]
  9. Johnson B. L., Fisher R. I., Bender R. A., DeVita V. T., Jr, Chabner B. A., Young R. C. Hexamethylmelamine in alkylating agent-resistant ovarian carcinoma. Cancer. 1978 Nov;42(5):2157–2161. doi: 10.1002/1097-0142(197811)42:5<2157::aid-cncr2820420511>3.0.co;2-7. [DOI] [PubMed] [Google Scholar]
  10. Kaneko T., LePage G. A. Growth characteristics and drug responses of a murine lung carcinoma in vitro and in vivo. Cancer Res. 1978 Jul;38(7):2084–2090. [PubMed] [Google Scholar]
  11. Lake L. M., Grunden E. E., Johnson B. M. Toxicity and antitumor activity of hexamethylmelamine and its N-demethylated metabolites in mice with transplantable tumors. Cancer Res. 1975 Oct;35(10):2858–2863. [PubMed] [Google Scholar]
  12. Legha S. S., Slavik M., Carter S. K. Hexamethylmelamine. An evaluation of its role in the therapy of cancer. Cancer. 1976 Jul;38(1):27–35. doi: 10.1002/1097-0142(197607)38:1<27::aid-cncr2820380106>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
  13. Rutty C. J., Connors T. A. In vitro studies with hexamethylmelamine. Biochem Pharmacol. 1977 Dec 15;26(24):2385–2391. doi: 10.1016/0006-2952(77)90446-4. [DOI] [PubMed] [Google Scholar]
  14. Rutty C. J., Connors T. A., Nguyen-Hoang-Nam, Do-Cao-Thang, Hoellinger H. In vivo studies with hexamethylmelamine. Eur J Cancer. 1978 Jun;14(6):713–720. doi: 10.1016/0014-2964(78)90308-0. [DOI] [PubMed] [Google Scholar]
  15. Salmon S. E., Hamburger A. W., Soehnlen B., Durie B. G., Alberts D. S., Moon T. E. Quantitation of differential sensitivity of human-tumor stem cells to anticancer drugs. N Engl J Med. 1978 Jun 15;298(24):1321–1327. doi: 10.1056/NEJM197806152982401. [DOI] [PubMed] [Google Scholar]
  16. Takita H., Didolkar M. S. Effect of hexamethylmelamine (NSC-13875) on small cell carcinoma of the lung (phase II study). Cancer Chemother Rep. 1974 May-Jun;58(3):371–374. [PubMed] [Google Scholar]
  17. Wilson W. L., Schroeder J. M., Bisel H. F., Mrazek R., Hummel R. P. Phase II study of hexamethylmelamine (NSC 13875). Cancer. 1969 Jan;23(1):132–136. doi: 10.1002/1097-0142(196901)23:1<132::aid-cncr2820230116>3.0.co;2-7. [DOI] [PubMed] [Google Scholar]
  18. Worzalla J. F., Johnson B. M., Ramirez G., Bryan G. T. N-demethylation of the antineoplastic agent hexamethylmelamine by rats and man. Cancer Res. 1973 Nov;33(11):2810–2815. [PubMed] [Google Scholar]
  19. Worzalla J. F., Kaiman B. D., Johnson B. M., Ramirez G., Bryan G. T. Metabolism of hexamethylmelamine-ring-14C in rats and man. Cancer Res. 1974 Oct;34(10):2669–2674. [PubMed] [Google Scholar]

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

RESOURCES