TRANSPLANTATION OF ALLOGENEIC AND XENOGENEIC (RAT) MARROW IN IRRADIATED MICE AS AFFECTED BY RADIATION EXPOSURE RATES
TRANSPLANTATION OF ALLOGENEIC AND XENOGENEIC (RAT) MARROW IN IRRADIATED MICE AS AFFECTED BY RADIATION EXPOSURE RATES
复制标题
受辐射暴露率影响的受辐射小鼠的同种异体和异种（大鼠）骨髓移植
作者：
N. Gengozian;D. Carlson;E. Allen
用137Cs或60Co照射器以不同的照射率对小鼠进行900-R或1200-R全身照射。每组小鼠按不同的暴露剂量接受静脉注射。异基因或异种(大鼠)骨髓细胞。在接受900R和异基因骨髓的患者中，以3.75R/min或19.8R/min的速率照射的患者的存活率没有增加，而以39.7R/min或53.4R/min的速率照射的患者的存活率增加。在四个辐射照射率组中，没有一组在60天的幸存者中检测到供体骨髓移植。在接受1200R和异基因骨髓的小鼠中，在研究的三种不同照射速率3.75R/min、39.7R/min和53.4R/min下，小鼠的存活率高于辐射对照组。然而，只有在两个曝光率较高的组中，供体骨髓的永久移植才有效。在不同的暴露速率下接受1200R照射的小鼠，然后接受异种骨髓治疗，结果基本上与同种异体移植组相同，即低暴露速率组没有永久移植物。在骨髓移植物丢失后的幸存者中检测到针对移植物抗原(大鼠红细胞)的抗体形成。在一组涉及无特定病原体的小鼠的实验中，获得了作为辐射暴露率函数的“中致死效应”的证据。在3.67R/min的低照射率下接受1050或1100R照射的动物，30天的死亡率高于辐射对照组。然而，当以53.4R/min的速率给予相同的总照射时，骨髓导致的存活率高于对照组。此外，低曝光率组在移植物丢失后形成了针对移植物抗原的抗体，并且供者的粒细胞在骨髓和脾中的持久性也减少了。这些数据强烈表明，小鼠的免疫机制对辐射暴露率很敏感，即暴露率越低，受辐射动物产生免疫反应的能力就越强，从而导致移植物的不完全吸收或丢失，并随后形成抗体。这些现象可能会发生，即使动物已经获得了100%的致死剂量，暴露时间的差异从几分钟到几个小时不等。本文还讨论了这些发现与辐射患者骨髓移植临床试验的相关性。
SUMMARY Mice were given 900-R or 1200-R total body irradiation at varying exposure rates with a 137Cs or 60Co irradiator. Groups of mice from each exposure rate received i.v. allogeneic or xenogeneic (rat) bone marrow cells. Of those receiving 900 R and allogeneic marrow, increased survival above the radiation controls was not obtained in those irradiated at a rate of 3.75 R/min or 19.8 R/min; increased survival was obtained in those irradiated at a rate of 39.7 R/min or 53.4 R/min. In none of the four radiation exposure rate groups was a donor marrow graft detected in the 60-day survivors. In those mice receiving 1200 R and allogeneic marrow, increased survival above the radiation controls was obtained for the three different exposure rates studied, 3.75 R/min, 39.7 R/min, and 53.4 R/min. Only in the two higher exposure rate groups, however, was a permanent transplant of donor marrow effected. Mice receiving 1200 R at varying exposure rates followed by xenogeneic marrow treatment showed essentially the same results as in the allogeneic groups, i.e., the absence of a permanent graft in the low exposure rate group. Antibody formation directed against graft antigens (rat red blood cells) was detected in the survivors following loss of the marrow graft. In a group of experiments involving specific pathogen-free mice, evidence for a “midlethal killing effect” as a function of radiation exposure rate was obtained. Animals receiving 1050 or 1100 R at the low exposure rate of 3.67 R/min and then treated with rat bone marrow showed greater 30-day mortality than the radiation control groups. When the same total exposures were given at the rate of 53.4 R/min, however, the marrow caused increased survival above that of the controls. Furthermore, the low exposure rate groups showed formation of antibody directed against graft antigen following loss of the graft and also a decrease in the persistence of donor granulocytes in the bone marrow and spleen. The data strongly suggest the immune mechanism of mice to be sensitive to rates of radiation exposure; i.e., the lower the exposure rate, the greater the ability of the irradiated animal to mount an immune response leading to an incomplete take or loss of the graft and subsequent formation of antibody. These phenomena can occur even though the animal has received a 100% lethal dose and the difference in expose time has ranged from a few minutes to a few hours. The relevance of these finding to clinical trials of marrow transplantation in irradiated patients is discussed.