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Changes of Oxygen Tension in Experimental Tumors after a Single Dose of X-Ray Irradiation¹

Departments of Radiology [F. G., K. J. L., J. F. D., G. B., H. M. S.] and Medicine (Radiation Oncology) [J. A. O., E. S. R.], Dartmouth-Hitchcock Medical Center, Hanover, New Hampshire 03755

Electron paramagnetic resonance oximetry was used to measure the partial pressure of oxygen (pO₂) in two types of tumor in vivo in C3H/HeJ mice. The pO₂ in MTG-B (high hypoxic fraction) and RIF-1 (low hypoxic fraction) tumors was monitored prior to and at several time points after a single dose of X-ray irradiation (up to 7 days after treatment). Initial values of pO₂ in RIF-1 (8.7 ± 1.1 mm Hg; n = 14) were higher than that of pO₂ in MTG-B (3.3 ± 0.5 mm Hg; n = 19). The pO₂ in both types of unirradiated tumors decreased slowly with tumor growth. Irradiation of tumors had a two-phase effect on pO₂: an initial sharp decrease in pO₂, followed by slow reoxygenation. After a 20-Gy radiation dose, the pO₂ was 2.2 ± 0.5 mm Hg at 6 h [significantly lower (P < 0.0001) than in control] and 3.2 ± 0.5 mm Hg at 48 h [significantly higher (P < 0.02) than in control] in MTG-B, and 5.4 ± 1.2 mm Hg at 24 h and 8.2 ± 1.0 mm Hg at 72 h in RIF-1. The time course for these changes in pO₂ was found to be independent of the doses in use in this study (10, 20, and 40 Gy). The occurrence of radiation-induced changes in pO₂ and the different time courses of these changes suggest that repeated monitoring of pO₂ in tumors during treatment could be used to enhance the efficacy of clinical treatments.

¹ This work was supported by American Cancer Society Grant BE-186, the Core Grant of the Norris Cotton Cancer Center CA-23108, and NIH Grant GM-51630. In addition, we used the facilities of the Illinois EPR Research Center at Dartmouth, which is supported by NIH grant RR-01811.

² On leave from the First Department of Surgery, Kagawa Medical School, 1750-1 Ikenobe Miki, Kagawa 761-07, Japan.

³ To whom requests for reprints should be addressed, at Radiation Oncology, 708 Vail Building, Dartmouth-Hitchcock Medical Center, Hanover, NH 03755.

⁴ On leave from the Institute of Nuclear Science "Vinca" Department, RMG-80, Belgrade, Yugoslavia.

Received 3/ 8/95. Accepted 4/21/95.