COMPARISON OF THE PHYSIOLOGICAL 



RESPONSE TO RADIATION AND TO 



RADIOMIMETIC CHEMICALS 



L. A. Elson* 

 Chester Beatty Research Institute, Royal Cancer Hospital, London 



I N a large amount of the experimental work on the physiological effects of 

 radiation, and the modification of these effects by chemical ' protective ' 

 agents or other means the criterion used has been the mean lethal dose. 

 Although this criterion provides some quantitative measure of the effect 

 of radiations it suffers from serious limitations, one of the most important 

 of which is that it gives little information on the various phases of radiation 

 response except insofar as ' grouping ' of deaths in time is concerned. 



A study of the phases of radiation response of the rat to uniform whole 

 body irradiation has been made by Lamerton, Elson and ChristensenI 

 and to non-uniform irradiation by Lamerton, Elson and Harris^. In 

 these studies an attempt was made to use the weight changes of young 

 growing rats as a measure of severity of physiological response to radiation, 

 and to relate these weight changes to effects on the circulating blood cells. 

 The changes in the growth curves were found to indicate clearly different 

 stages of the radiation response. 



Based on these results and some more recent evidence it is now possible 

 to attempt in Figure 1 to provide a convenient reference diagram relating 

 the blood changes to the various phases of radiation response as indicated 

 ]:)y the weight response curves. This is necessarily only an approximation 

 as naturally considerable variations from this pattern are found in the 

 behaviour of individual animals, but it does represent a useful diagrammatic 

 picture of the average response of rats to whole body X-irradiation with 

 doses of the order of 400-600r. 



It is convenient to distinguish four phases of response based on the growth 

 curves. Phase I is the initial weight loss phase and lasts for about 2 to 

 4 days immediately following irradiation. The animal loses w^eight steadily 

 during this phase and a measure of the amount of weight lost is conveniently 

 given by the parameter L^. The lymphocytes fall rapidly during phase I 

 and reach their minimum value usually by the end of this phase. Phase II 

 is the first recovery phase. An abrupt change in the weight curve occurs 

 and the animal resumes its normal growth rate, and continues to grow 

 normally until about the twelfth day after irradiation. During phase II 

 the neutrophils which start to fall in phase I continue to fall after a slight 

 recovery and reach a minimum at about the end of the phase. Lymphocytes 

 begin a gradual recovery during phase II. Phase III is the second weight 

 drop phase. This second weight drop occurs frequently in rats receiving 



* British Empire Cancer Campaign Research Fellow. 



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