Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1980 Apr;41(4):517–522. doi: 10.1038/bjc.1980.93

Combination studies with misonidazole and a cis-platinum complex: cytotoxicity and radiosensitization in vitro.

I J Stratford, C Williamson, G E Adams
PMCID: PMC2010266  PMID: 7190019

Abstract

cis-Dichlorodiammineplatinum(II) (cis-Pt(II) can act as a radiosensitizer of hypoxic mammalian cells in vitro. Used in combination with misonidazole the level of sensitization achieved is greater than that seen with either drug alone, and it is suggested that these compounds sensitize by independent mechanisms. For cells held at 37 degrees C, cis-Pt(II) shows much greater toxicity to hypoxic cells than to aerobic cells. In combination with misonidazole, no additional cytotoxic effect is shown towards aerobic cells than that seen for cis-Pt(II) alone. However, there is additional killing of hypoxic cells when they are treated with both drugs.

Full text

PDF
517

Selected References

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

  1. Adams G. E., Clarke E. D., Flockhart I. R., Jacobs R. S., Sehmi D. S., Stratford I. J., Wardman P., Watts M. E., Parrick J., Wallace R. G. Structure-activity relationships in the development of hypoxic cell radiosensitizers. I. Sensitization efficiency. Int J Radiat Biol Relat Stud Phys Chem Med. 1979 Feb;35(2):133–150. doi: 10.1080/09553007914550151. [DOI] [PubMed] [Google Scholar]
  2. Adams G. E., Flockhart I. R., Smithen C. E., Stratford I. J., Wardman P., Watts M. E. Electron-affinic sensitization. VII. A correlation between structures, one-electron reduction potentials, and efficiencies of nitroimidazoles as hypoxic cell radiosensitizers. Radiat Res. 1976 Jul;67(1):9–20. [PubMed] [Google Scholar]
  3. Ash D. V., Smith M. R., Bugden R. D. Distribution of misonidazole in human tumours and normal tissues. Br J Cancer. 1979 May;39(5):503–509. doi: 10.1038/bjc.1979.93. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Dische S., Saunders M. I., Lee M. E., Adams G. E., Flockhart I. R. Clinical testing of the radiosensitizer Ro 07-0582: experience with multiple doses. Br J Cancer. 1977 May;35(5):567–579. doi: 10.1038/bjc.1977.90. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Moore B. A., Palcic B., Skarsgard L. D. Radiosensitizing and toxic effects on the 2-nitroimidazole Ro-07-0582 in hypoxic mammation cells. Radiat Res. 1976 Sep;67(3):459–473. [PubMed] [Google Scholar]
  8. Nias A. H., Bocian E., Laverick M. The mechanism of action of cis-dichloro-bis (isopropylamine) trans dihydroxyplatinum IV (CHIP) on Chinese hamster and C3H mouse tumor cells and its interaction with X-irradiation. Int J Radiat Oncol Biol Phys. 1979 Aug;5(8):1341–1344. doi: 10.1016/0360-3016(79)90666-7. [DOI] [PubMed] [Google Scholar]
  9. Richmond R. C., Powers E. L. Radiation sensitization of bacterial spores by cis-dichlorodiammineplatinum(II). Radiat Res. 1976 Nov;68(2):251–257. [PubMed] [Google Scholar]
  10. Richmond R. C., Zimbrick J. D., Hykes D. L. Radiation-induced DNA damage and lethality in E. coli as modified by the antitumor agent cis-dichlorodiammineplatinum (II). Radiat Res. 1977 Aug;71(2):447–460. [PubMed] [Google Scholar]
  11. Roberts J. J., Thomson A. J. The mechanism of action of antitumor platinum compounds. Prog Nucleic Acid Res Mol Biol. 1979;22:71–133. doi: 10.1016/s0079-6603(08)60799-0. [DOI] [PubMed] [Google Scholar]
  12. Roizin-Towle L., Hall E. J. Studies with bleomycin and misonidazole on aerated and hypoxic cells. Br J Cancer. 1978 Feb;37(2):254–260. doi: 10.1038/bjc.1978.34. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Sridhar R., Koch C., Suterland R. Cytotoxicity of two nitroimidazole radiosensitizers in an in vitro tumor model. Int J Radiat Oncol Biol Phys. 1976 Nov-Dec;1(11-12):1149–1157. doi: 10.1016/0360-3016(76)90088-2. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Sutherland R. M., Eddy H. A., Bareham B., Reich K., Vanantwerp D. Resistance to adriamycin in multicellular spheroids. Int J Radiat Oncol Biol Phys. 1979 Aug;5(8):1225–1230. doi: 10.1016/0360-3016(79)90643-6. [DOI] [PubMed] [Google Scholar]
  16. Szumiel I., Nias A. H. The effect of combined treatment with a platinum complex and ionizing radiation on chinese hamster ovary cells in vitro. Br J Cancer. 1976 Apr;33(4):450–458. doi: 10.1038/bjc.1976.70. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES