TRANSPLANTATION OF ALLOGENEIC AND XENOGENEIC (RAT) MARROW IN IRRADIATED MICE AS AFFECTED BY RADIATION EXPOSURE RATES

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. © 1969 by The Williams & Wilkins Co.