Radiation Effects on Lymphocytes 129 



9.2 days while that for the rat is only 2.4 days. 53 Irradiation with 10 r reduced 

 the 10 per cent survival time both of the rat and the human lymphocytes. 

 The lymphocytes of both species have approximately the same sensitvitv 

 to small doses of irradiation. However, the 10 per cent survival time of the 

 human lymphocytes irradiated with 1000 r was 1.7 days, while that of 

 the rat was only 0.4 days. The slower destructive action of irradiation on 

 human cells is dependent on the difference in the longevity of the lympho- 

 cytes of the two species. 



I have mentioned the theory that irradiation does not kill lymphocytes 

 but accelerates the aging and death of the cells. I developed this concept 

 as a result of studies by dark field microscopy on the death of irradiated 

 and nonirradiated lymphocytes 47 and as a result of a comparison of the 

 radiosensitivity of human and rodent lymphocytes. :,?> In reviewing the litera- 

 ture for this paper, I find that in vivo studies have led other workers to 

 express similar theories. Isaacs in 1932 stated that irradiation causes accelera- 

 tion of maturation, senility, and death of blood cells.- And prior to that, in 

 1926 Nemenow 38 stated that in the ovary and other tissues the irradiated 

 cell "both ages and perishes more rapidly, but it perishes exactly in the same 

 way as it would have perished if it were to die, so to say, of a natural death." 

 The theory does not answer the questions: what is the normal physiologic 

 aging and death of the lymphocyte and how does irradiation accelerate these 

 factors? 



The finding that the lymphocyte has about the same sensitivity as the 

 mitotic cell has led me to speculate that the lymphocyte and the mitotic cell 

 have a similar metabolic process which is radiosensitive."' 5 The radiosensi- 

 tivity of cells in mitosis has been considered by many workers to be due to 

 inhibition of the synthesis of desoxyribonucleic acid. The synthesis of DNA 

 may be an important function of the lymphocyte, and interference with 

 this function by x-rays may cause cell death. 



IN VIVO STUDIES 



Four different mechanisms have been proposed by various workers for 

 the in vivo reactions of lymphocytes to x-rays. First, the irradiation may 

 affect the lymphocytes by direct action on the cells. Second, the irradiation 

 may inhibit the production of lymphocytes by acting on cells in mitosis. 

 Third, the lymphocytes may be destroyed by indirect, humoral, or toxic 

 effects induced by the irradiation. Finally, irradiation may be similar to 

 other modes of stress which stimulate the adrenal glands to secrete cortical 

 hormones deleterious to lymphocytes. 



The indirect or humoral action of x-rays on Lymphocytes has been sug- 

 gested by clinical observations that irradiation of the spleen or of one group 



