ADMINISTRATION OF A HEMOGLOBIN SOLUTION DECREASES HYPOXIA AND INCREASES RADIATION RESPONSE IN A RAT MAMMARY-CARCINOMA

Administration of an ultrapurified bovine hemoglobin solution (8 ml/kg, iv) to female Fisher 344 rats bearing the 13672 mammary carcinoma implanted subcutaneously in the hind leg reduced the hypoxic fraction of the tumor from 49 to 36% with normal air breathing and to 28% with carbogen (95% oxygen/5% carbon dioxide) breathing. When administration of the hemoglobin solution was followed by single dose (10, 20, or 30 Gray) local radiation therapy, the dose modifying factor was 1.5 with air breathing and 2.7 with carbogen breathing. For fractionated radiation therapy, 2, 3, or 4 Gray was delivered locally daily for 5 days. When the hemoglobin solution was administered prior to each radiation fraction and air breathing maintained, there was a 1.8-fold increase in tumor growth delay. When daily hemoglobin solution administration was accompanied by carbogen breathing, there was a 2.6-fold increase in tumor growth delay. Less frequent administration of the hemoglobin solution (alternate days, twice weekly or once weekly) resulted in 1.5- to 1.7-fold increases in tumor growth delay. The greatest increases in tumor oxygenation occurred shortly after administration of the hemoglobin solution; in fact at 12 h post administration of the hemoglobin solution, the tumors appeared to be more hypoxic than prior to administration of the hemoglobin solution. by 24 h post administration of the hemoglobin solution, the oxygen tension profile of the tumors were returning to pretreatment levels. further investigation of this ultrapurified hemoglobin solution in cancer is warranted. (C) 1995 Wiiey-Liss, Inc.