THE PHYSIOLOGICAL RESPONSE TO RADIATION AND TO RADIOMIMETIC CHEMICALS 



resemble that of X-radiation with regard to red cells or neutrophils. The 

 behaviour of lymphocytes is, however, very similar to that following X- 

 irradiation throughout all four phases. With CB 1348 practically all blood 

 cells have returned to normal by the end of Phase III. A few exceptions to 

 this, however, have been noticed, but these are rare. In these, after the 

 neutrophilia, the neutrophils, instead of returning to normal values and 

 remaining normal, continue to fall. The animal then shows a second weight 

 drop preceded by a general haemorrhagic state as with X-irradiation. 



-2 



8 10 13 n 16 



18 20 22 2t 26 28 



day 



Figure 4. Weight and Blood Response to nitrogen mustard derivative CB 1348 



It appears, therefore, that both Myleran and CB 1348 are each only 

 partially radiomimetic, the former showing mainly the myeloid effects and 

 the latter mainly the lymphoid effects of X-radiation. By combining the 

 two chemicals it should be possible to produce a much more complete 

 imitation of the response to X-radiation. This has been tested using a dose 

 of CB 1348 of 12-5mg/kg given by intraperitoneal injection and a dose of 

 Myleran of 12 -5 mg/kg given by mouth. The response is shown in Figure 5 

 and although this dosage was found to correspond with about 250 r of 

 X-radiation the resemblance of the response to that pictured in Figure 1 

 (corresponding to 400-600 r X-radiation) can be seen clearly. The dose 



240 



