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British Journal of Cancer logoLink to British Journal of Cancer
. 1979 Oct;40(4):641–648. doi: 10.1038/bjc.1979.230

Radiosensitization of E. coli B/r by 9-anilinoacridines.

P B Roberts, W A Denny, B F Cain
PMCID: PMC2010075  PMID: 387061

Abstract

Six anilinoacridine derivatives have been tested for the ability to act as radiosensitizers. Two gave good sensitization at concentrations of 100 microM or less. Both of these are known to possess significant activity against experimental tumours, and one (m-AMSA) is in Phase II clinical trial as a chemotherapeutic drug. Anilinoacridines may have potential as drugs with both a chemotherapeutic and radiosensitizing role. In spite of their structural similarity, the 2 derivatives which sensitize do so by different mechanisms. Compound VI behaves like a typical hypoxic cell sensitizer but Compound I (m-AMSA) interferes with the accumulation of sublethal damage in either the presence or absence of O2. The latter also displays a post-irradiation sensitizing effect. Differences in mechanism may be related to the relative DNA-binding abilities and electronic differences between the 2 drugs.

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Selected References

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

  1. Anghileri L. J. Uptake of iodine-131-labelled atabrine by Ehrlich ascites tumour and by sarcoma S-180 BALB. Nature. 1966 Aug 20;211(5051):878–878. doi: 10.1038/211878a0. [DOI] [PubMed] [Google Scholar]
  2. Arlett C. F. The influence of post-irradiation conditions on the survival of Chinese hamster cells after gamma-irradiation. Int J Radiat Biol Relat Stud Phys Chem Med. 1970;17(6):515–526. doi: 10.1080/09553007014550651. [DOI] [PubMed] [Google Scholar]
  3. Atwell G. J., Cain B. F., Denny W. A. Potential antitumor agents. 24. Dicationic analogues of the 4'-(9-acridinylamino)alkanesulfonanilides. J Med Chem. 1977 Sep;20(9):1128–1134. doi: 10.1021/jm00219a004. [DOI] [PubMed] [Google Scholar]
  4. Atwell G. J., Cain B. F., Seelye R. N. Potential antitumor agents. 12. 9-Anilinoacridines. J Med Chem. 1972 Jun;15(6):611–615. doi: 10.1021/jm00276a011. [DOI] [PubMed] [Google Scholar]
  5. Brown J. M. Cytotoxic effects of the hypoxic cell radiosensitizer Ro 7-0582 to tumor cells in vivo. Radiat Res. 1977 Dec;72(3):469–486. [PubMed] [Google Scholar]
  6. Cain B. F., Atwell G. J., Denny W. A. Potential antitumor agents. 16.4'-(Acridin-9-ylamino)methanesulfonanilides. J Med Chem. 1975 Nov;18(11):1110–1117. doi: 10.1021/jm00245a013. [DOI] [PubMed] [Google Scholar]
  7. Cain B. F., Baguley B. C., Denny W. A. Potenial antitumor agents. 28. Deoxyribonucleic acid polyintercalating agents. J Med Chem. 1978 Jul;21(7):658–668. doi: 10.1021/jm00205a013. [DOI] [PubMed] [Google Scholar]
  8. Cain B. R., Wilson W. R., Baguley B. C. Structure-activity relationships for thiolytic cleavage rates of antitumor drugs in the 4'-(9-acridinylamino)methanesulfonanilide series. Mol Pharmacol. 1976 Nov;12(6):1027–1035. [PubMed] [Google Scholar]
  9. 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]
  10. Fowler J. F., Adams G. E., Denekamp J. Radiosensitizers of hypoxic cells in solid tumors. Cancer Treat Rev. 1976 Dec;3(4):227–256. doi: 10.1016/s0305-7372(76)80012-6. [DOI] [PubMed] [Google Scholar]
  11. Fuks Z., Smith K. C. Effect of quinacrine on x-ray sensitivity and the repair of damaged DNA in Escherichia coli K-12. Radiat Res. 1971 Oct;48(1):63–73. [PubMed] [Google Scholar]
  12. Hall E. J., Roizin-Towle L. Hypoxic sensitizers: radiobiological studies at the cellular level. Radiology. 1975 Nov;117(2):453–457. doi: 10.1148/117.2.453. [DOI] [PubMed] [Google Scholar]
  13. Leenhouts H. P., Chadwick K. H. An analysis of synergistic sensitization. Br J Cancer Suppl. 1978 Jun;3:198–201. [PMC free article] [PubMed] [Google Scholar]
  14. Mohindra J. K., Rauth A. M. Increased cell killing by metronidazole and nitrofurazone of hypoxic compared to aerobic mammalian cells. Cancer Res. 1976 Mar;36(3):930–936. [PubMed] [Google Scholar]
  15. 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]
  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. Stratford I. J., Adams G. E. Effect of hyperthermia on differential cytotoxicity of a hypoxic cell radiosensitizer, Ro-07-0582, on mammalian cells in vitro. Br J Cancer. 1977 Mar;35(3):307–313. doi: 10.1038/bjc.1977.44. [DOI] [PMC free article] [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. Town C. D., Smith K. C., Kaplan H. S. Repair of X-ray damage to bacterial DNA. Curr Top Radiat Res Q. 1973 Jul;8(4):351–399. [PubMed] [Google Scholar]
  20. 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]
  21. Wilson W. B., Cain B. F., Baguley B. C. Thiolytic cleavage of the anti-tumour compound 4'-(9-acridinylamino)-methanesulphon-m-anisidine (m-AMSA, NSC 156 303) in blood. Chem Biol Interact. 1977 Aug;18(2):163–178. doi: 10.1016/0009-2797(77)90004-7. [DOI] [PubMed] [Google Scholar]

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