The influence of haemoglobin affinity for oxygen on tumour radiosensitivity.

Appropriate control of the affinity of haemoglobin for oxygen is fundamental to the efficient oxygenation of our tissues. Important modifiers of this relationship are pH, CO2 concentration and the intraerythrocytic level of 2,3-diphosphoglycerate (2,3-DPG). We have studied the influence of haemoglobin affinity on the radiosensitivity of the RIF-1 sarcoma in the mouse. Changes in haemoglobin affinity were induced by exposing donor mice to either 10% oxygen, normal air, or 100% oxygen for 48 h. Blood was drawn from these animals and exchanged transfused into tumour-bearing mice immediately before irradiation. Transfusion of blood from mice breathing 10% oxygen carried a lowered haemoglobin affinity and produced marked radiosensitization of the tumours in the recipients; transfusion with normal blood had no significant effect and transfusions from mice breathing 100% oxygen caused a small increase in radioresistance. Measurements of the level of 2,3-DPG in the blood of these groups showed higher concentrations in the oxygen-deprived animals than in controls but no significant change in animals exposed to 100% oxygen. These results demonstrate that alterations in haemoglobin affinity, probably resulting from changes in 2,3-DPG levels, can have a powerful influence on tumour radiosensitivity. We feel that this mechanism could have considerable clinical importance.