Hirst D G, Wood P J
Br J Cancer. 1987 May;55(5):487-91. doi: 10.1038/bjc.1987.99.
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.
对血红蛋白与氧气亲和力进行适当控制，是我们组织高效氧合的基础。这种关系的重要调节因子是pH值、二氧化碳浓度和红细胞内2,3-二磷酸甘油酸（2,3-DPG）的水平。我们研究了血红蛋白亲和力对小鼠RIF-1肉瘤放射敏感性的影响。通过将供体小鼠暴露于10%氧气、正常空气或100%氧气环境中48小时，诱导血红蛋白亲和力发生变化。在照射前，从这些动物身上采集血液，并立即将其交换输给荷瘤小鼠。输注来自呼吸10%氧气小鼠的血液，其血红蛋白亲和力降低，使受体小鼠的肿瘤产生明显的放射增敏作用；输注正常血液没有显著影响，而输注来自呼吸100%氧气小鼠的血液则导致放射抗性略有增加。对这些组小鼠血液中2,3-DPG水平的测量显示，缺氧动物中的浓度高于对照组，但暴露于100%氧气的动物中没有显著变化。这些结果表明，血红蛋白亲和力的改变，可能是由2,3-DPG水平变化引起的，对肿瘤放射敏感性有强大影响。我们认为这种机制可能具有相当大的临床重要性。
