INCREASED TUMOR OXYGENATION AND RADIATION SENSITIVITY IN 2 RAT-TUMORSBY A HEMOGLOBIN-BASED, OXYGEN-CARRYING PREPARATION

The rat 13762 mammary carcinoma and the rat 9L gliosarcoma were grown subcutaneously in a hind limb of female, Fisher 344 rats. The oxygen c ontent of the tumors was determined using an Eppendorf pO(2) histograp h. Fifty-to-sixty oxygen measurements were made per tumor and there we re 8-to-10 animals per group. The percent of pO(2) readings less than or equal to 5 mmHg in the mammary carcinoma was 49%, this was decrease d to 34% by administration of the hemoglobin preparation (8 ml/kg) and further decreased to 29% when carbogen (95% O-2/5% CO2) breathing was added to administration of the hemoglobin preparation. The percent of pO(2) readings less than or equal to 5 mmHg in the gliosarcoma was 49 %, this was decreased to 24% by administration of the hemoglobin prepa ration and further decreased to 0% when carbogen breathing was added t o administration of the hemoglobin preparation. Therapeutic response w as assessed over a single-dose range of radiation therapy (10, 20 and 30 Gray). The dose modifying factor produced by the hemoglobin prepara tion/air was 1.6 and by the hemoglobin preparation/carbogen was 2.7 in the rat 13762 mammary carcinoma. The dose modifying factor produced b y the hemoglobin preparation/air was 1.9 and by the hemoglobin prepara tion/carbogen was 2.9 in the rat 9L gliosarcoma. Administration of a h emoglobin-based oxygen carrier reduced tumor hypoxia and increased tum or response to radiation therapy.