HISTOLOGICAL CHANGES AFTER IRRADIATION 1135 



which no visible changes occur while they are in the resting state, but 

 which do appear as abnormal, often multipolar, mitoses when the cells 

 undergo division, frequently leading to death of the cells. Somatic 

 lethal mutations or chromosome aberrations may perhaps explain the 

 death of cells long after irradiation of their parent cells (Muller, 1950). 

 This may be the explanation of the failure to persist of early regeneration 

 of erythroblasts and myelocytes in the beginning recovery of marrow 

 made aplastic by irradiation. In the latter case it may be that the 

 progeny of the irradiated, but not visibly damaged, reticular cells are 

 destined to develop somatic lethal mutations. Against this suggestion is 

 the fact that attempts at regeneration in this tissue seem to occur in 

 waves, whereas, on the proposed explanation, it should be a continuous 

 process with gradual predominance of those myelopoietic cells which had 

 not been damaged. 



The normal hepatic epithelial cell undergoes mitosis only rarely. If a 

 large part of the liver is removed, the remaining liver cells undergo such 

 tremendous mitotic activity that in a few days a large part of the liver is 

 regenerated — this process, as might be expected, being faster in young 

 rats than in older ones. The liver cells normally are markedly resistant 

 to radiation. But the rapidly dividing cells of regenerating liver are 

 easily damaged by radiation, which calls forth great numbers of chromo- 

 some aberrations and cells with multipolar mitoses (Brues and Rietz, 

 1951). It is quite probable that if the liver cells were irradiated suffici- 

 ently intensely before partial hepatectomy, the irradiation damage which 

 would become manifest in the regenerating liver would be so extensive as 

 to interfere with or even prohibit the regenerative process. 



One cannot speak of the absolute sensitivity of a particular cell type in 

 a complex organism, for the cell in question cannot be dissociated from its 

 environment and its functional state at a given moment. Changes in 

 environment affect its response to irradiation just as changes in its 

 activity also modify its reaction. Examples are seen in the greater 

 sensitivity of lymphocytes in lymphatic nodules compared to those 

 scattered in the lamina propria, or in bone cells of the metaphysis as 

 opposed to the more resistant cells of compact bone. Furthermore, every 

 cell strain becomes more radioresistant in vitro. 



The radiosensitivity of an organ is not simply a reflection of the radio- 

 sensitivity of certain of its cells, for one organ may have tremendous 

 regenerative capacities while another may not. For instance, blood cell 

 formation may be wiped out from the bone marrow of a femur in a few 

 days after irradiation, but this marrow can regenerate completely from 

 its more radioresistant reticular cells. However, with the same amount 

 of radiation, an area of skin may require weeks to manifest its complete 

 damage and regeneration will come only from surrounding nonirradiated 

 skin; furthermore, the friable skin may persist for years. It is difficult to 



