The effect of imidazole, administered 5 minutes before, or immediately after irradiation (800 rads), on survival and erythropoiesis was studied. The results showed that imidazole increased the survival of irradiated mice when administered 4.5 hours before irradiation, 5 minutes before irradiation, or immediately after irradiation. The highest reduction of radiation lethality was obtained when imidazole was administered 5 minutes before irradiation. Using 59 Fe incorporation into blood and spleen as a measure of erythropoietic activity, it was found that imidazole given either before or after irradiation does not affect the initial radiation-induced depression of erythropoietic activity but it does promote the subsequent recovery of the erythropoietic system. When the pre- or postirradiation imidazole treatment was combined with a postirradiation administration of erythropoietin, there was a further increase in both erythropoiesis and survival.

The present study shows the effect of erythropoietin administered one hour post-irradiation on the erythropoietic recovery and survival of gamma-irradiated mice pretreated with a number of radioprotective agents and radioprotective mixtures. Both polycythemic and normal mice were used in these studies. Erythropoietin administered one hour post-irradiation to AET-protected mice produced more rapid erythropoietic recovery (as measured by blood and spleen 59 Fe uptake) and better survival than in AET-protected mice which were not treated with erythropoietin. Doses of erythropoietin ranging from one to twenty units produced an equivalent effect. The erythropoietic recovery pattern of AET-protected mice given erythropoietin post-irradiation was studied to determine the effect of time (1 to 10 days) and increasing radiation exposure dose (700 to 1000 rads) on erythropoietic recovery using the radioiron technique. The possibility of further increasing erythropoietic recovery and survival in mice after irradiation by using the erythropoietin post-irradiation treatment in combination with other radioprotective agents or mixtures has been investigated. The results show that erythropoietin treatment post-irradiation increased erythropoietic recovery in AET-protected mice exposed to radiation doses of up to 1000 rads. If the radioprotective agent or mixture increased erythropoietic recovery and survival, the erythropoietin post-irradiation treatment would further increase both these factors.

Erythropoietic stem cell damage and recovery after treatment with radio-protective agents followed by gamma irradiation was measured in transfusion-induced polycythemic mice in conjunction with 59 Fe red cell incorporation as the indicator of erythropoietic activity. In irradiated mice, the administration of S-2 aminoethylisothioureadihydrobromide (AET) prior to irradiation results in less initial damage to the blood and spleen, and this is responsible for the earlier recovery of the erythropoietic system. Blood and spleen 59 Fe values at 1 or 7 days after irradiation with 200 or 700 rads, respectively, can be used to compare the relative value of different sulfhydryl agents in aiding survival. Using the split-dose technique, it was shown that AET given prior to the second radiation dose provided protection to the hematopoietic system and increased survival. However, AET prior to the first radiation dose (200 rads) did not produce any increased protective effect over that produced by the first radiation dose when the mice were irradiated 10 days later.