The Response of a Transplantable Tumor to Fractionated Irradiation: 1. X Rays and the Hypoxic Cell Radiosensitizer Ro-07-0582

The response of a transplantable mammary carcinoma in CBA mice to single doses and two or five fractions of X rays, with and without the hypoxic cell sensitizer Ro-07-0582, has been tested using delay of tumor regrowth as the measure of response. In the tumors treated with X rays alone the processes of repair of sublethal injury, and reoxygenation between fractions, appeared to counteract each other so that no extra dose was needed to achieve a particular level of damage when fractionated irradiation was used. When Ro-07-0582 was administered shortly before each radiation dose, however, the tumor cells were made more uniformly radiosensitive, so that without the complication of hypoxia and reoxygenation their repair capacity could be measured. The repair capacity measured in this tumor was approximately 50-70% of that observed in skin. The response of the tumor to different treatments has been expressed in relation to the response of mouse skin, as an example of normal tissue. With X rays alone, more tumor delay could be achieved for a standard level of skin reaction if the dose were fractionated, due presumably to the difference in repair capacities and reoxygenation in the tumor. The tumor delay for a constant skin reaction was further increased when Ro-07-0582 was present at 0.67 mg/g body weight. "X-ray dose enhancement ratios" of 1.7 for single doses, 1.6 for two fractions, and 1.2 for five fractions, were measured at a particular level of tumor response.