HEMATOLOGIC EFFECTS OF RADIATION 1079 



of total-body exposure without reducing survival below the 75 per cent 

 that is expected from the earlier spleen-shielding studies (Jacobson, 

 Simmons, Marks, Gaston, et al., 1951). In contrast to animals with 

 spleen shielding and thus no irradiation of the spleen, these animals 

 become moderately anemic and develop a severe leukopenia that persists 

 beyond the twelfth day. Recovery of erythropoiesis as judged by the 

 circulating reticulocytes begins by the sixth day, Fig. 16-22 (Jacobson, 

 Marks, et al., 1951). Histologic studies show that recovery of the 

 blood-forming tissue is qualitatively complete by 10-12 days (Jacobson, 

 Simmons, Marks, Gaston, et al., 1951). Even with dosages of 400, 500, 

 or 600 r to the spleen and 1025 r to the body, survival is significantly 

 higher (59, 50, and 34 per cent, respectively) than in mice exposed to 

 1025 r without spleen shielding (1.1 per cent). Recovery of hemato- 

 poietic tissue is delayed progressively longer with increasing increments of 

 the total-body dose delivered to the spleen. These data indicate that the 

 capacity of the splenic tissue to elaborate the factor is still partially 

 retained or recovery of the tissue in the spleen that produces the factor 

 occurs early enough to enhance survival even with doses as high as 

 600 r to the spleen and 1025 r to the body. These observations tend to 

 add support to the hypothesis that the factor (or factors) responsible for 

 recovery from radiation injury under these circumstances is derived from 

 more primitive but more radioresistant cells, such as reticular cells, 

 rather than from the free cells of the hematopoietic system, such as 

 lymphocytes and granulocytes. The spleen is, for all practical purposes, 

 devoid of these free cells after a dose of 500 r, whereas the basic reticular 

 network remains "histologically " intact. It is interesting that, following 

 the delivery of a lethal dose to the body (1025 r) and an LD 50 (500-600 r) 

 to the spleen, ca. 50 per cent of the animals survive. 



EFFECT OF COMBINED PROPHYLACTIC 

 AND THERAPEUTIC MEASURES 



The fact that a reduction in the mortality of animals exposed to lethal 

 dosages of total-body X irradiation could be effected by pretreatment 

 with estrogens (Treadwell, Gardner, and Lawrence, 1943) as well as by 

 spleen shielding (Jacobson et al., 1949) suggested to Simmons, Jacobson, 

 and Marks (1950-1951) that these two measures might produce an addi- 

 tive effect on survival. Accordingly, Simmons tested this hypothesis and 

 found that (1) mortality of mice exposed to 1025 r of total-body X irradia- 

 tion was 100 per cent, (2) 61.5 per cent of the mice survived this dose if 

 estrogens were given prior to irradiation, (3) 82.3 per cent survived if the 

 spleen was shielded during exposure to 1025 r, and (4) 100 per cent 

 survived 1025 r if the techniques of pretreatment with estrogens as well 

 as spleen shielding were employed. Bethard, Skirmont, and Jacobson 

 (1950) and Bethard and Jacobson (1951), employing the same general 



