Modification of Radiation Injury of Murine Intestinal Clonogenic Cells and B-16 Melanoma by PGI2 or Flurbiprofen
Prostaglandins (PC s) protect several types of cells in vivo from ionizing radiation. Many human tumors secrete excessive PG’s, which may result in some degree of tumor protection from radiation treatment. In contrast, PG-blocking agents might sensitize tumors to radiation. To assess a possible role of PG’s and PG-blocking agents in modifying normal tissue or tumor radiation sensitivity, either PGI2 (the most protective natural PG found to date) or Flurbiprofen (a cyclooxygenase inhibitor) was given to mice before irradiation with cesium-137. The effects of these agents on the radiosensitivity of intestinal clonogenic cells or a B-16 melanoma were measured. PGI2 increased the D° of intestinal clonogenic cell survival from about 1.15 ± 0.13 Gy in controls to 1.45 ± 0.15 Gy. Flurbiprofen had no effect on the intestinal clonogenic cell survival curve. PGI2 also protected the B-16 melanoma, but Flurbiprofen protected the melanoma to an even greater extent, mainly through an increase in the shoulder. Flurbiprofen may switch the arachidonic acid cascade to other pathways such as the 5-lipoxygenase pathway, and leukotrienes have also been shown to protect from radiation. Tumor radiosensitization may occur only through blocking all pathways of the cascade or by blocking tumor receptor sites.
KeywordsMelanoma Cell Radiation Injury Murine Bone Marrow Arachidonic Acid Cascade Lung Coloni
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- 3.Hanson, W. R., this volumeGoogle Scholar
- 4.Hanson, W. R., and DeLaurentiis, K. Comparison of in vivo murine intestinal radiation protection by the E-series prostaglandins E1, E2, 16-16 dm E2, and Misoprostol. In preparation.Google Scholar
- 12.Honn, K. V. Prostacyclin/thromboxane ratios in tumor growth and metastasis. In: “Prostaglandins and Related Lipids,” Vol. 2. T. J. Powles, R. S. Bockman, K. V. Honn, and P. Ramwell, eds. Alan R. Liss, Inc., New York, 1982, pp. 733–752.Google Scholar
- 13.Goodwin, J. S. Prostaglandin E and cancer growth potential for immunotherapy with prostaglandin synthetase inhibitors. In: “Progress in Cancer Research and Therapy; Augmenting Agents in Cancer Therapy,” Vol. 16. E. M. Hersh, M. A. Chirigos, and M. J. Mastrangelo, eds. Raven Press, New York, 1981, pp. 393–415.Google Scholar
- 17.MacDougall, R. H., Duncan, W., and Clark, B. M. The effect of flurbiprofen on stem cell survival following X irradiation. In: Reference 12, pp. 819–823.Google Scholar
- 19.Hellman, K., and Pym, B. A. Antitumor activity of flurbiprofen in vivo and in vitro. In: Reference 12, pp. 767–774.Google Scholar
- 21.Northway, M. G., Libshitz, H. L., Osborne, B. M., Feldman, M. S., Mamel, J. J., West, J. H., and Szwarc, I. A. Radiation esophagitis in the opossum: Radio-protection with indomethacin. Gastroenterology 78: 833–837, 1980.Google Scholar
- 22.Northway, M. G., Bennett, A., Carroll, M. A., Eastwood, G. L., Feldman, M. S., Libshitz, H. L., Mamel, J. J., and Szwarc, I. A. Effects of antiinflammatory agents and radiotherapy on esophageal mucosa and tumors in animals. In: Reference 12, pp. 799–802.Google Scholar