L. A. ELSON 



after treatment. A general picture of the weight and blood response to 

 Myleran is given in Figure 3. There is very little initial weight drop in 

 response to Myleran and little effect on lymphocytes. In fact, Phase I can 

 be considered as practically non-existent compared with X-irradiation 

 {Figure 1) and the response to Myleran over this phase is quite unlike that to 

 X-irradiation. There is practically no initial weight loss and no fall in 

 Ivmphocytes. Neutrophils commence a steady fall but not nearly as rapidly 

 as after X-irradiation. In Phase II the neutrophils continue to fall and as 

 with X-radiation reach their minimum at about the end of this phase. 

 The behaviour of the red cells during phase II is also very similar to that 

 following X-irradiation. With doses of Myleran which cause a second 

 weight drop a rapid fall of red cells takes place starting from about the 

 eighth day after treatment. From this time a general haemorrhagic state 

 is usually observed and can easily be demonstrated by plucking a small 

 area of fur from the animal's chest, when petechial haemorrhages appear 

 almost immediately. This haemorrhagic state usually persists until at 

 least 20 days after the original dose of Myleran. Lympocytes may show a 

 slight fall during phase II, but owing to the large variations which occur in 

 the number of these cells in normal rats the fall is often barely significant. 

 Phase III \n response to Myleran closely resembles that of X-irradiation except, 

 of course, in behaviour of lymphocytes. In animals showing a s^ond weight 

 drop, red cells continue to fall and reach their minimum at the end of this 

 phase. Neutrophils show a steady recovery throughout the phase. Phase IV, 

 the final recovery phase, again corresponds closely with that of X-radiation. 

 With toxic doses of Myleran, deaths always occur during phase III, never 

 in phase I. For example, in one experiment, 5 rats treated with 20 mg kg 

 Myleran all died between 10 and 12 days after treatment. In all cases 

 death was caused by massive haemorrhage, usually in the stomach. 



Myleran thus shows mainly the myeloid effect of X-radiation and has little 

 effect on lymphoid tissue. Thus, referring to Figure 1, phase I which may be 

 considered associated with lymphoid effects, is not shown by Myleran. Phase 

 III, however, with its associations with red cell and neutrophil depression 

 is strongly represented by Myleran. 



Nitrogen Mustard CB 1348 {Figure 4) — In contrast to Myleran Phase I of the 

 response to CB 1348 is practically identical to that shown by X-radiation. 

 The initial weight drop and fall in lymphocytes may be slightly more pro- 

 longed but resembles very closely the pattern followed after X-irradiation. 

 With toxic doses of CB 1 348 deaths nearly all occur during phase I. Phase II, 

 however, shows considerable diflferences from X-radiation, mainly in the 

 very marked neutrophilia which occurs as the neutrophils recover from 

 their minimum fall at about the end of phase I. The neutrophilia is at its 

 maximum at about 10 days after treatment at which time the number of 

 circulating neutrophils may be three or four times the normal value. A slight 

 rise in the neutrophil curves at about 8 to 10 days after X-irradiation has 

 often been observed and this, as now seen, probably corresponds to the peak 

 of the neutrophilia in response to nitrogen mustard {see Figure 1). No sharp 

 fall in red cells in response to CB 1348 occurs during phase II but there is 

 often a slight fall with a minimum at about the time of the maximum degree 

 of neutrophilia. Thus phase II of the response to CB 1348 does not at all 



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