HEMATOLOGIC EFFECTS OF RADIATION 1077 



to the number of cells available in the shielded or implanted tissue and 

 the amount of the factor available determines the survival of the animal. 

 It would appear as though the repair process must be initiated in a mini- 

 mum number of cells in the body of the irradiated animal to ensure sur- 

 vival of the animal exposed to dosages of 1000 r or more. 



The Humoral Theory of Cell Regeneration. In mice and rabbits which 

 had spleen shielding or spleen transplants, regeneration may occur from 

 the scattered "free cells" in the lymphatic tissues and bone marrow that 

 survive the radiation, but heteroplastic regeneration from reticular cells 

 is prominent. Thus colonization from the shielded tissue and repopula- 

 tion by multiplication of these colonized cells, if a factor at all, is only one 

 aspect of the recovery process. The shielded tissue in some way restores 

 the functional capacity of the reticular cells to repopulate the hemato- 

 poietic tissues. The shielded tissue may likewise restore the functional 

 capacity of the residual free cells, which are not destroyed by irradiation, 

 to multiply and thus repopulate the hematopoietic tissues. Cells coming 

 from the shielded or implanted tissue cannot at the moment be dis- 

 tinguished from the residual free cells. If the cells, which do migrate out 

 from the shielded tissue, do "lodge" in hematopoietic tissue, then it is 

 also possible that they too contribute by division and multiplication and 

 also by elaboration of the factor (or factors) under discussion. 



Clamping Off Splenic Circulation during Irradiation-shielding Procedure. 

 The survival of mice in which the circulation to the shielded spleen is 

 clamped off during exposure of the animal to 1025 r and in which the 

 clamp is released immediately after irradiation is approximately the 

 same as survival in animals with spleen shielding but without clamping 

 (Jacobson, Simmons, Marks, and Eldredge, 1951; Jacobson, Simmons, 

 Marks, Gaston, et al., 1951). Histologic recovery of the hematopoietic 

 system is the same as in the spleen-shielded animals without clamping of 

 the splenic pedicle. This observation was convincing evidence that the 

 presence of shielded tissue in the circulation was not required during the 

 period of irradiation in order for survival to be enhanced and hemato- 

 poietic regeneration to proceed. Reintroduction of the spleen into the 

 circulation after irradiation could thus be considered an effective post- 

 irradiation "therapeutic" approach to the problem. 



Splenectomy after Spleen Shielding. Surgical extirpation of the ini- 

 tially shielded spleen at intervals after exposure of mice to 1025 r of total- 

 body X irradiation shows that a beneficial effect (survival > 70 per cent 

 and early regeneration of hematopoietic tissue) has already been exerted 

 if the shielded spleen is left intact in the circulation for 1 hour (Jacobson, 

 Simmons, Marks, Gaston, et al., 1951). Leaving the spleen in the circula- 

 tion for longer periods such as 6 or 24 hours or 2 or more days does not 

 increase the percentage of animals surviving. In a previous communica- 



