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British Journal of Cancer logoLink to British Journal of Cancer
. 1982 Jun;45(6):869–877. doi: 10.1038/bjc.1982.139

Skin sensitization by misonidazole: a demonstration of uniform mild hypoxia.

F A Stewart, J Denekamp, V S Randhawa
PMCID: PMC2011034  PMID: 7093121

Abstract

Skin reactions on irradiated mouse feet were used to measure the radiosensitization of normal tissues by misonidazole (MISO). Fractionation schedules of 1, 2, 5 and 10 daily doses of X-rays were combined with either 100 mg/kg or 670 mg/kg MISO. When unanaesthetized mice were irradiated in air, significant sensitization was observed with both the high and low drug doses, in all fractionation schedules. There was no decrease in sensitization with fractionation, even using fractions as small as 5 Gy. This indicates that many of the cells in mouse skin may be marginally hypoxic, and that sensitization at low doses is possible. Irradiation in O2 without MISO rendered the skin more sensitive to X-rays than in air. MISO given 30 min before single doses of radiation further sensitized the skin, but for 10 fractions in O2 no MISO sensitization was detected. There was little evidence for cytotoxic killing in skin by MISO. Repair of radiation damage was slightly reduced when MISO was present, during or after irradiation.

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Selected References

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  1. Arcangeli G., Nervi C., Mauro F. Misonidazole also radiosensitizes some normal tissue. Br J Radiol. 1980 Jan;53(625):44–45. doi: 10.1259/0007-1285-53-625-44. [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., Morris C., Field S. B. The response of a transplantable tumor to fractionated irradiation. II. Fast neutrons. Radiat Res. 1976 Oct;68(1):93–103. [PubMed] [Google Scholar]
  4. Denekamp J., Harris S. R. The response of a transplantable tumor to fractionated irradiation. 1. X rays and the hypoxic cell radiosensitizer Ro-07-0582. Radiat Res. 1976 Apr;66(1):66–75. [PubMed] [Google Scholar]
  5. Denekamp J., Michael B. D., Harris S. R. Hypoxic cell radiosensitizers: comparative tests of some electron affinic compounds using epidermal cell survival in vivo. Radiat Res. 1974 Oct;60(1):119–132. [PubMed] [Google Scholar]
  6. Denekamp J., Michael B. D., Rojas A., Stewart F. A. Thiol radioprotection in vivo: the critical role of tissue oxygen concentration. Br J Radiol. 1981 Dec;54(648):1112–1114. doi: 10.1259/0007-1285-54-648-1112-c. [DOI] [PubMed] [Google Scholar]
  7. Denekamp J. Residual radiation damage in mouse skin 5 to 8 months after irradiation. Radiology. 1975 Apr;115(1):191–195. doi: 10.1148/115.1.191. [DOI] [PubMed] [Google Scholar]
  8. Dische S., Gray A. J., Zanelli G. D. Clinical testing of the radiosensitiser Ro-07-0582. II. Radiosensitisation of normal and hypoxic skin. Clin Radiol. 1976 Apr;27(2):159–166. doi: 10.1016/s0009-9260(76)80138-9. [DOI] [PubMed] [Google Scholar]
  9. Dische S., Saunders M. I., Flockhart I. R., Lee M. E., Anderson P. Misonidazole-a drug for trial in radiotherapy and oncology. Int J Radiat Oncol Biol Phys. 1979 Jun;5(6):851–860. doi: 10.1016/0360-3016(79)90070-1. [DOI] [PubMed] [Google Scholar]
  10. Dixon B. The effect of radiation on the growth of vertebrae in the tails of rats. I. Single doses of x-rays and the effect of oxygen. Int J Radiat Biol Relat Stud Phys Chem Med. 1967;13(4):355–368. doi: 10.1080/09553006814550321. [DOI] [PubMed] [Google Scholar]
  11. Douglas B. G., Fowler J. F. The effect of multiple small doses of x rays on skin reactions in the mouse and a basic interpretation. Radiat Res. 1976 May;66(2):401–426. [PubMed] [Google Scholar]
  12. Field S. B., Morris C. C. Does misonidazole enhance radiation injury to the central nervous system? Br J Cancer. 1981 Jun;43(6):878–880. doi: 10.1038/bjc.1981.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fowler J. F., Denekamp J., Delapeyre C., Harris S. R., Sheldon P. W. Skin reactions in mice after multifraction x-irradiation. Int J Radiat Biol Relat Stud Phys Chem Med. 1974 Mar;25(3):213–223. doi: 10.1080/09553007414550271. [DOI] [PubMed] [Google Scholar]
  14. Fowler J. F., Denekamp J., Page A. L., Begg A. C., Field S. B., Butler K. Fractionation with x rays and neutrons in mice: response of skin and C 3 H mammary tumours. Br J Radiol. 1972 Apr;45(532):237–249. doi: 10.1259/0007-1285-45-532-237. [DOI] [PubMed] [Google Scholar]
  15. Gonzalez D. G., Breur K. Dose-modifying effect of misonidazole on the radiation response of growing cartilage in mice. Br J Cancer Suppl. 1978 Jun;3:235–236. [PMC free article] [PubMed] [Google Scholar]
  16. Guichard M., de Langen-Omri F., Malaise E. P. Influence of misonidazole on the radiosensitivity of a human melanoma in nude mice: time-dependent increase in surviving fraction. Int J Radiat Oncol Biol Phys. 1979 Apr;5(4):487–489. doi: 10.1016/0360-3016(79)90811-3. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Hendry J. H. Quantitation of the radiotherapeutic importance of naturally-hypoxic normal tissues from collated experiments with rodents using single doses. Int J Radiat Oncol Biol Phys. 1979 Jul;5(7):971–976. doi: 10.1016/0360-3016(79)90602-3. [DOI] [PubMed] [Google Scholar]
  19. Hendry J. H. Sensitization of hypoxic normal tissue. Br J Cancer Suppl. 1978 Jun;3:232–234. [PMC free article] [PubMed] [Google Scholar]
  20. Hendry J. H., Sutton M. L. Care with radiosensitizers. Br J Radiol. 1978 Nov;51(611):927–928. doi: 10.1259/0007-1285-51-611-927. [DOI] [PubMed] [Google Scholar]
  21. Henk J. M., Kunkler P. B., Smith C. W. Radiotherapy and hyperbaric oxygen in head and neck cancer. Final report of first controlled clinical trial. Lancet. 1977 Jul 16;2(8029):101–103. doi: 10.1016/s0140-6736(77)90116-7. [DOI] [PubMed] [Google Scholar]
  22. Hornsey S., Field S. B. The effects of single and fractionated doses of X-rays and neutrons on the oesophagus. Eur J Cancer. 1979 Apr;15(4):491–498. doi: 10.1016/0014-2964(79)90084-7. [DOI] [PubMed] [Google Scholar]
  23. Johnson R. J., Burke T. R., Drechsel R., Subjeck J. R. Physiological changes which may result from in vivo experimental conditions. Br J Cancer Suppl. 1980 Apr;4:106–107. [PMC free article] [PubMed] [Google Scholar]
  24. Nakatsugawa S., Sugahara T. Inhibition of X-ray-induced potentially lethal damage (PLD) repair by cordycepin (3'-deoxyadenosine) and enhancement of its action by 2'-deoxycoformycin in Chinese hamster hai cells in the stationary phase in vitro. Radiat Res. 1980 Nov;84(2):265–275. [PubMed] [Google Scholar]
  25. Potten C. S., Howard A. Radiation depigmentation of mouse hair: the influence of local tissue oxygen tension on radiosensitivity. Radiat Res. 1969 Apr;38(1):65–81. [PubMed] [Google Scholar]
  26. Sakamoto K., Aritake S. Effects of misonidazole on tumor cell radiation sensitivity and potentially lethal damage repair in vivo and in vitro. Eur J Cancer Clin Oncol. 1981 Jul;17(7):825–830. doi: 10.1016/0014-2964(81)90239-5. [DOI] [PubMed] [Google Scholar]
  27. Stewart F. A., Denekamp J. Sensitization of mouse skin to X irradiation by moderate heating. Radiology. 1977 Apr;123(1):195–200. doi: 10.1148/123.1.195. [DOI] [PubMed] [Google Scholar]
  28. Suit H. D., Maimonis P., Michaels H. B., Sedlacek R. Comparison of hyperbaric oxygen and misonidazole in fractionated irradiation of murine tumors. Radiat Res. 1981 Aug;87(2):360–367. [PubMed] [Google Scholar]
  29. 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]
  30. Suzuki N., Withers H. R., Hunter N. Radiosensitization of mouse spermatogenic stem cells by Ro-07-0582. Radiat Res. 1977 Mar;69(3):598–601. [PubMed] [Google Scholar]
  31. Travis E. L., Parkins C. S., Holmes S. J., Down J. D. Effect of misonidazole on radiation injury to mouse spinal cord. Br J Cancer. 1982 Mar;45(3):469–473. doi: 10.1038/bjc.1982.76. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Yuhas J. M. Misonidazole enhancement of acute and late radiation injury to the rat spinal cord. Br J Cancer. 1979 Jul;40(1):161–163. doi: 10.1038/bjc.1979.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Yuhas J. M., Yurconic M., Kligerman M. M., West G., Peterson D. F. Combined use of radioprotective and radiosensitizing drugs in experimental radiotherapy. Radiat Res. 1977 May;70(2):433–443. [PubMed] [Google Scholar]

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