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. 1980 Nov;42(5):684–691. doi: 10.1038/bjc.1980.302

Enhanced killing of mammalian cells by radiation combined with m-AMSA.

P B Roberts, B C Millar
PMCID: PMC2010567  PMID: 6893934

Abstract

m-AMSA is an intercalating agent at present on Phase II trial as a chemotherapeutic drug. A 30 min exposure of Chinese hamster (Line V79-753B) cells to submicromolar concentrations of m-AMSA killed 50% of the cells. The survivors had an enhanced sensitivity to radiation-induced cell killing. Depending upon the conditions, m-AMSA enhanced the radiation effect by either a decrease in the survival-curve shoulder or by an increase in slope. m-AMSA may act partly by suppressing the accumulation of sublethal damage but, if so, recovery from damage as measured in split-dose experiments with cells pretreated with the drug is not affected to its radiation effect from selective toxicity to cells in a radioresistant phase of the cell cycle cannot be excluded. Radiation and the drug interacted to give increased cell killing, even when the exposures to each agent were separated in time. It is concluded that m-ASMA may behave like actinomycin D and adriamycin, and enhance clinical radiation responses. In vivo testing to determine the effect of m-AMSA on the therapeutic index is recommended.

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Selected References

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

  1. Belli J. A., Piro A. J. The interaction between radiation and adriamycin damage in mammalian cells. Cancer Res. 1977 Jun;37(6):1624–1630. [PubMed] [Google Scholar]
  2. Byfield J. E., Lynch M., Kulhanian F., Chan P. Y. Cellular effects of combined adriamycin and x-irradiation in human tumor cells. Int J Cancer. 1977 Feb 15;19(2):194–204. doi: 10.1002/ijc.2910190209. [DOI] [PubMed] [Google Scholar]
  3. Cooke B. C., Fielden E. M., Johnson M. Polyfunctional radiosensitizers. I. Effects of a nitroxyl biradical on the survival of mammalian cells in vitro. Radiat Res. 1976 Jan;65(1):152–162. [PubMed] [Google Scholar]
  4. Cysyk R. L., Shoemaker D., Adamson R. H. The pharmacologic disposition of 4'-(9-acridinylamino)methanesulfon-m-anisidide in mice and rats. Drug Metab Dispos. 1977 Nov-Dec;5(6):579–590. [PubMed] [Google Scholar]
  5. D'ANGIO G. J. Clinical and biologic studies of actinomycin D and roentgen irradiation. Am J Roentgenol Radium Ther Nucl Med. 1962 Jan;87:106–109. [PubMed] [Google Scholar]
  6. Denny W. A., Atwell G. J., Cain B. F. Potential antitumor agents. 26. Anionic congeners of the 9-anilinoacridines. J Med Chem. 1978 Jan;21(1):5–10. doi: 10.1021/jm00199a002. [DOI] [PubMed] [Google Scholar]
  7. Donaldson S. S., Glick J. M., Wilbur J. R. Letter: Adriamycin activating a recall phenomenon after radiation therapy. Ann Intern Med. 1974 Sep;81(3):407–408. doi: 10.7326/0003-4819-81-3-407. [DOI] [PubMed] [Google Scholar]
  8. ELKIND M. M., WHITMORE G. F., ALESCIO T. ACTINOMYCIN D: SUPPRESSION OF RECOVERY IN X-IRRADIATED MAMMALIAN CELLS. Science. 1964 Mar 27;143(3613):1454–1457. doi: 10.1126/science.143.3613.1454. [DOI] [PubMed] [Google Scholar]
  9. Elkind M. M., Sutton-Gilbert H., Moses W. B., Kamper C. Sub-lethal and lethal radiation damage. Nature. 1967 Jun 10;214(5093):1088–1092. doi: 10.1038/2141088a0. [DOI] [PubMed] [Google Scholar]
  10. Gormley P. E., Sethi V. S., Cysyk R. L. Interaction of 4'-(9-acridinylamino)methanesulfon-m-anisidide with DNA and inhibition of oncornavirus reverse transcriptase and cellular nucleic acid polymerases. Cancer Res. 1978 May;38(5):1300–1306. [PubMed] [Google Scholar]
  11. Millar B. C., Fielden E. M., Millar J. L. Interpretation of survival-curve data for Chinese hamster cells, line V-79 using the multi-target, multi-target with initial slope, and alpha, beta equations. Int J Radiat Biol Relat Stud Phys Chem Med. 1978 Jun;33(6):599–603. doi: 10.1080/09553007814550521. [DOI] [PubMed] [Google Scholar]
  12. Piro A. J., Taylor C. C., Belli J. A. Interaction between radiation and drug damage in mammalian cells. I. Delayed expression of actinomycin D/x-ray effects in exponential and plateau phase cells. Radiat Res. 1975 Aug;63(2):346–362. [PubMed] [Google Scholar]
  13. Roberts P. B., Denny W. A., Cain B. F. Radiosensitization of E. coli B/r by 9-anilinoacridines. Br J Cancer. 1979 Oct;40(4):641–648. doi: 10.1038/bjc.1979.230. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Rozencweig M., Von Hoff D. D., Cysyk R. L., Muggia F. M. m-AMSA and PALA: two new agents in cancer chemotherapy. Cancer Chemother Pharmacol. 1979;3(3):135–141. doi: 10.1007/BF00262414. [DOI] [PubMed] [Google Scholar]
  15. Saladino C. F., Ben-Hur E. Quinacrine-enhanced killing response of cultured Chinese hamster cells by X-rays. Res Commun Chem Pathol Pharmacol. 1978 Dec;22(3):629–632. [PubMed] [Google Scholar]
  16. Shoemaker D. D., Legha S. S., Cysyk R. L. Selective localization of 4'-(9-acridinylamino)-methanesulfon-m-anisidide in B 16 melanoma. Pharmacology. 1978;16(4):221–225. doi: 10.1159/000136771. [DOI] [PubMed] [Google Scholar]
  17. Sinclair W. K. Cyclic x-ray responses in mammalian cells in vitro. Radiat Res. 1968 Mar;33(3):620–643. [PubMed] [Google Scholar]
  18. Tobey R. A., Deaven L. L., Oka M. S. Kinetic response of cultured Chinese hamster cells to treatment with 4'-[(9-acridinyl)-amino]methanesulphon-m-anisidide-HCl. J Natl Cancer Inst. 1978 May;60(5):1147–1153. doi: 10.1093/jnci/60.5.1147. [DOI] [PubMed] [Google Scholar]
  19. Waring M. J. DNA-binding characteristics of acridinylmethanesulphonanilide drugs: comparison with antitumour properties. Eur J Cancer. 1976 Dec;12(12):995–1001. doi: 10.1016/0014-2964(76)90066-9. [DOI] [PubMed] [Google Scholar]

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