HISTOLOGICAL CHANGES AFTER IRRADIATION 1105 



cytes die; (2) a phase of cleanup (8 hours to 2 days), when debris is 

 removed by macrophages and possibly in part through lymphatic 

 channels, exposing a condensed epithelial stroma and blood vessels in 

 the cortex and leaving a few surviving lymphocytes in the medulla; 

 (3) a phase of inactivity (2 to 9 days), during which shrinkage continues 

 and the connective tissue becomes prominent ; and (4) a phase of regenera- 

 tion (10 days to four weeks), characterized by a repopulation with 

 lymphocytes, proceeding outward from the medulla. The stromal or 

 reticular cells are not damaged by this or even much larger amounts of 

 irradiation. The H assail' s bodies, formed of masses of epithelial cells, 

 are unaffected. There are suggestions of new formation of Hassall's 

 bodies from stromal cells at 14 days. 



At lower doses fewer cells die, the inactive period is shorter, and regen- 

 eration is more rapid. This sequence of changes is somewhat similar to 

 that already described for the lymphatic tissue. As in that tissue, the 

 reaction in different species is the same to equal single doses of X rays, 

 irrespective of the variations in LD 50 levels for these species. 



External (3 rays sufficient to kill about 20 per cent of the mice (5000 rep) 

 do not affect the thymus in these animals. Qualitatively, the reactions 

 to fast and slow neutrons are the same as to X rays. Quantitatively, the 

 X-ray /fast-neutron ratio has been estimated to be roughly 5 and the 

 X-ray/slow-neutron ratio to be roughly 1 (Murray, 1948b). 



Long-continued, daily low doses of total-body y rays gradually cause 

 depletion of lymphocytes — with 8.8 r first at 6 months and with 4.4 r at 

 8 months (Spargo et al., 1951). With 1.1 r greater depletion than in 

 controls is first observed at 10 months. Both in this group and in the 

 4.4-r group attempts at regeneration are present at 14 and 16 months. 

 In all these animals there is a striking increase in mast cells in the depleted 

 organs as well as in the surrounding connective tissue. Plasma cells are 

 not prominent. 



The depletion of the thymus following internal irradiation is similar to 

 that produced by X rays, but it usually occurs more gradually and is 

 more prolonged. Also, because of localization of the isotopes, the deple- 

 tion is not always uniform. Irregular depletion results from the uneven 

 distribution of a emitters within the thymus. For example, after admin- 

 istration of plutonium, areas containing the isotope, as seen in autoradio- 

 graphs of adjacent sections, are depleted, whereas nearby uncontaminated 

 areas are not. When the thymus is irradiated as a result of activity 

 deposited elsewhere, as Sr s9 or Y 91 in the sternum, or Y 91 or cerium- 

 praseodymium (275-day) in the lung, there is a gradient of damage. 

 The parts nearest the localized isotopes suffer the most damage, which 

 decreases perceptibly away from the focus. However, as might be 

 expected, the highly diffusible Na 24 in doses of 50 to 80 juc/g in mice 

 (considerably above the LD 50 30-day level) causes a rapid, diffuse, and 



