Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1977 Mar;35(3):299–306. doi: 10.1038/bjc.1977.43

Interaction of hyperthermia and the hypoxic cell sensitizer Ro-07-0582 on the EMT6 mouse tumour.

N M Bleehen, D J Honess, J E Morgan
PMCID: PMC2025289  PMID: 856237

Abstract

The combination of hyperthermia and the hypoxic cell radiosensitizer Ro-07-0582 has been investigated on the EMT6 tumour implanted into the legs of BALB/c mice. Treatments at a drug dose of 1 mg/g over a range of waterbath temperatures from 37 to 45 degrees C are described. The surviving clonogenic fraction following treatment was assayed in vitro. Measurements of intra-tumour temperature have been made, and shown to be better correlated with the cytocidal effect on the tumour than the waterbath temperature. No significant effect of Ro-07-0582 was observed at 37 degrees C. However, marked cytotoxicity due to the drug was seen at intra-tumour temperatures above 42-5 degrees C for 1 h. These were in addition to the cytocidal effect of the hyperthermia. The results are discussed in relation to the distribution of temperatures and hypoxic cell populations throughout the tumour.

Full text

PDF
299

Selected References

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

  1. Adams G. E. Chemical radiosensitization of hypoxic cells. Br Med Bull. 1973 Jan;29(1):48–53. doi: 10.1093/oxfordjournals.bmb.a070956. [DOI] [PubMed] [Google Scholar]
  2. Brown J. M. Selective radiosensitization of the hypoxic cells of mouse tumors with the nitroimidazoles metronidazole and Ro 7-0582. Radiat Res. 1975 Dec;64(3):633–647. [PubMed] [Google Scholar]
  3. Denekamp J., Harris S. R. Tests of two electron-affinic radiosensitizers in vivo using regrowth of an experimental carcinoma. Radiat Res. 1975 Feb;61(2):191–203. [PubMed] [Google Scholar]
  4. Foster J. L., Conroy P. J., Searle A. J., Willson R. L. Metronidazole (Flagyl): characterization as a cytotoxic drug specific for hypoxic tumour cells. Br J Cancer. 1976 May;33(5):485–490. doi: 10.1038/bjc.1976.78. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Gerweck L. E., Gillette E. L., Dewey W. C. Killing of Chinese hamster cells in vitro by heating under hypoxic or aerobic conditions. Eur J Cancer. 1974 Oct;10(10):691–693. doi: 10.1016/0014-2964(74)90009-7. [DOI] [PubMed] [Google Scholar]
  6. Hahn G. M., Braun J., Har-Kedar I. Thermochemotherapy: synergism between hyperthermia (42-43 degrees) and adriamycin (of bleomycin) in mammalian cell inactivation. Proc Natl Acad Sci U S A. 1975 Mar;72(3):937–940. doi: 10.1073/pnas.72.3.937. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Hermens A. F., Barendsen G. W. Changes of cell proliferation characteristics in a rat rhabdomyosarcoma before and after x-irradiation. Eur J Cancer. 1969 May;5(2):173–189. doi: 10.1016/0014-2964(69)90065-6. [DOI] [PubMed] [Google Scholar]
  9. Kal H. B., Hahn G. M. Kinetic responses of murine sarcoma cells to radiation and hyperthermia in vivo and in vitro. Cancer Res. 1976 Jun;36(6):1923–1929. [PubMed] [Google Scholar]
  10. Kal H. B., Hatfield M., Hahn G. M. Cell cycle progression of murine sarcoma cells after x irradiation or heat shock. Radiology. 1975 Oct;117(1):215–217. doi: 10.1148/117.1.215. [DOI] [PubMed] [Google Scholar]
  11. Kim S. H., Kim J. H., Hahn E. Q. Letter: Enhanced killing of hypoxic tumour cells by hyperthemia. Br J Radiol. 1975 Oct;48(574):872–874. doi: 10.1259/0007-1285-48-574-872-c. [DOI] [PubMed] [Google Scholar]
  12. Kim S. H., Kim J. H., Hahn E. W. The radiosensitization of hypoxic tumor cells by hyperthermia. Radiology. 1975 Mar;114(3):727–728. doi: 10.1148/114.3.727. [DOI] [PubMed] [Google Scholar]
  13. Little J. B., Hahn G. M., Frindel E., Tubiana M. Repair of potentially lethal radiation damage in vitro and in vivo. Radiology. 1973 Mar;106(3):689–694. doi: 10.1148/106.3.689. [DOI] [PubMed] [Google Scholar]
  14. McNally N. J. The effect of an hypoxic cell sensitizer on tumour growth delay and cell survival. Implications for cell survival in situ and in vitro. Br J Cancer. 1975 Nov;32(5):610–618. doi: 10.1038/bjc.1975.268. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Peters L. J. Modification of the radiocurability of a syngeneic murine squamous carcinoma by its site of growth, by electron-affinic drugs, and by ICRF 159. Br J Radiol. 1976 Aug;49(584):708–715. doi: 10.1259/0007-1285-49-584-708. [DOI] [PubMed] [Google Scholar]
  17. Rockwell S. C., Kallman R. F., Fajardo L. F. Characteristics of a serially transplanted mouse mammary tumor and its tissue-culture-adapted derivative. J Natl Cancer Inst. 1972 Sep;49(3):735–749. [PubMed] [Google Scholar]
  18. Rockwell S., Frindel E., Tubiana M. A technique for determining the proportion of the clonogenic cells in S phase in ENT6 cell cultures and tumors. Cell Tissue Kinet. 1976 Jul;9(4):313–323. doi: 10.1111/j.1365-2184.1976.tb01279.x. [DOI] [PubMed] [Google Scholar]
  19. Rockwell S., Kallman R. F. Cellular radiosensitivity and tumor radiation response in the EMT6 tumor cell system. Radiat Res. 1973 Feb;53(2):281–294. [PubMed] [Google Scholar]
  20. Suit H. D., Shwayder M. Hyperthermia: potential as an anti-tumor agent. Cancer. 1974 Jul;34(1):122–129. doi: 10.1002/1097-0142(197407)34:1<122::aid-cncr2820340118>3.0.co;2-r. [DOI] [PubMed] [Google Scholar]
  21. Sutherland R. M. Selective chemotherapy of noncycling cells in an in vitro tumor model. Cancer Res. 1974 Dec;34(12):3501–3503. [PubMed] [Google Scholar]
  22. Twentyman P. R., Bleehen N. M. Studies of "potentially lethal damage" in EMT6 mouse tumour cells treated with bleomycin either in vitro or in vivo. Br J Cancer. 1975 Oct;32(4):491–501. doi: 10.1038/bjc.1975.251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Twentyman P. R., Bleehen N. M. The sensitivity to bleomycin of a solid mouse tumour at different stages of growth. Br J Cancer. 1974 Nov;30(5):469–472. doi: 10.1038/bjc.1974.222. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES