Hyperbaric Oxygen and Radiobiology of a C3H Mouse Mammary Carcinoma 2

A series of radiation dose-tumor control response assays was performed on the first-to-fourth generation isotransplants of a C3H/J mouse mammary carcinoma for radiation administered under four different conditions: hypoxia, a clamp across the root of the tumor-bearing part for 1 minute before treatment; air, animal respiring air at one atmosphere of pressure; O2 30 or 44 psi, animal respiring pure oxygen at 30 or 44 psi for 15 minutes before and during local tumor irradiation. When radiation was administered as a single dose (v = 1) to 250 mm3 tumors, high pressure oxygen was only modestly effective in reducing the tumor control dose (TCD50); TCD50 hypoxia/O2 30 psi and TCD50 hypoxia/O2 44 psi were only 1.2 and 1.3, respectively. However, for similar treatment of 0.6 mm3 tumors and of even smaller "microcolonies," the ratios TCD50 hypoxia/O2 44 psi were 2.5 and 3.2, respectively. These results are discussed with respect to simple tumor models so as to estimate the proportion of hypoxic cells present in tumors under normal conditions and the influence of oxygen breathed at increased pressure on that proportion. High pressure oxygen was found much more effective when combined with fractionated irradiation (v = 10) than with single-dose therapy. Thus TCD50 hypoxia/O2 30 psi was 2.2 (v = 10) instead of 1.2 (v = 1). Finally, the ratio TCD50 hypoxia = 10/v = 1 was 2.15. These results are reviewed and inferences drawn as to the extent of tumor cell proliferation between treatments, repair of sublethal radiation injury by hypoxic cells, and the movement of cells from the hypoxic compartment to the aerobic compartment during fractionated irradiation (v = 10) under normal conditions.