1096 RADIATION BIOLOGY 



changes are probably secondary to effects produced in other organs. On 

 the other hand, iron pigment from ingested erythrocytes accumulates in 

 macrophages in the reparative phase after irradiation, and brown pigment 

 develops in the skin. 



Inter-phase Nucleus. One of the first changes to be seen in sections as 

 well as in living tissue cultures is a clumping of chromatin. This may 

 occur in both sensitive and resistant cell strains. It is probably reversi- 

 ble, since it may be seen in all types of cells of the body a short time after 

 irradiation and, depending on the dosage and the cell type, may or may 

 not disappear after a few hours. Other changes, probably not reversible, 

 include vacuolization of chromatin particles and nucleoli and thickening 

 of the nuclear membrane. In the course of the next few hours such cells 

 may show progressive pyknosis, the nuclear material condensing into 

 one, two, or three large chromatin masses (with or without vacuoles). 

 Sometimes the nuclei may disintegrate without passing through a 

 pyknotic stage. There is nothing specific about these nuclear changes 

 after irradiation, for similar effects may be produced by a variety of toxic 

 agents. 



In addition to these changes, nuclei may show marked budding in 

 certain cell types (hepatic epithelium, megakaryocytes), particularly 

 after long-continued action of radioactive isotopes accumulating in the 

 organ. Multilobular nuclei may be found in myelocytes after irradia- 

 tion. The swelling of nuclei is believed to be one of the most constant 

 results of irradiation (Failla and Sugiura, 1939). It is clearly seen in the 

 intestinal or gastric epithelium during the regenerating phase (Pierce, 

 1948). A pronounced swelling of the nucleus has not been a striking 

 feature of irradiated cells in tissue culture (W. Bloom, unpublished 

 observations). 



Dividing Cells. One of the most striking nuclear effects of irradiation 

 is the rapid cessation, after 200 to 800 r, of practically all mitosis in all 

 the organs which normally are in a state of continuous regeneration. 

 This interference with cellular division may be apparent about \-i to 1 

 hour after irradiation and may last 12 to 15 hours or much longer. The 

 cause of this inhibition is not known. In many tissues its duration 

 varies roughly with the dose. It is equally remarkable that "not all 

 mitoses are inhibited, even in a heavily irradiated tissue culture" (Shields 

 Warren, 1942, 1943). Most cells which had undergone the first morpho- 

 logically evident mitotic changes seem to go through the rest of the 

 process, although they may show lagging or otherwise damaged chromo- 

 somes. Fragmented chromosomes are thought to heal either with or 

 without visible defects, but, in all such cases, genie material is undoubt- 

 edly lost. In total mounts of the cornea of amphibian larvae a marked 

 clumping and eventual pyknosis of the chromatin at any stage of mitosis 



