EFFECT OF WHOLE-BODY IRRADIATION ON 



THYMUS FUNCTION AND LYMPHOCYTE 



HOMEOSTASIS* 



Donald Metcalf 



Walter and Eliza Hall Institute, Royal Melbourne Hospital, 

 Melbourne, Victoria 



INTRODUCTION 



The occurrence of leukaemia in man following exposure to ionizing irradiation 

 was first documented by Aubertin^. Subsequently, Krebs et al.'^ and Furth 

 and Furth^ described the induction of leukaemia in mice by whole-body 

 irradiation. These observations have since been amply confirmed. 



Whilst it is likely that ionizing irradiation may induce leukaemia in a small 

 number of cases by direct mutagenic effects, the elegant experiments of 

 Kaplan-*' ^ have shown that, in mice, in the majority of cases, the induction 

 of leukaemia is by an indirect mechanism. 



The thymus plays a major role in this indirect process. Thymectomy, 

 performed either before or after irradiation substantially reduces the subse- 

 quent incidence of leukaemia. Stimuli, arising from the irradiated tissues, 

 appear capable of affecting the degeneration-regeneration cycle in the 

 thymus following irradiation and determine whether or not neoplasia occurs 

 in this organ. In addition, following irradiation, the thymus has been 

 shown to influence the appearance of leukaemia in the other lymphoid tissues 

 by means of a non-cellular influence produced by the thymus^ 



Metcalf' has shown that the thymus produces a lymphocytosis stimulating 

 factor (L.S.F.) and that in lymphoid leukaemia, both in humans and mice, 

 excessive levels of L.S.F. are present. 



EFFECT OF W^HOLE-BODY IRRADIATION ON LYMPHOCYTE LEVELS 



When young adult C57BL mice are exposed to a single dose of 250 r whole- 

 body irradiation, there occurs the well-known post-irradiation depression of 

 circulating lymphocyte levels (Figure 1). Gradual recovery to pre-irradiation 

 levels occurs in 20 to 30 days. If such mice are observed for the duration 

 of their subsequent life, they are found to develop a permanent lympho- 

 cytosis — this lymphocytosis first becomes apparent 2 to 3 months after 

 irradiation. 



Thus the response to irradiation, in the mouse, is a biphasic one. Studies 

 made on mice in the acute, lymphopcnic, phase have sho\vn** that if such 

 mice are grafted with normal, unirradiated, isologous thymic tissue, the 

 lymphopenia is lessened and such mice achieve normal lymphocyte levels 



* This work was jointly sponsored by the Anti-Cancer Council of N'ictoria and the 

 National Institutes of Health, Washington, Grant No. C-2547. 



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