456 RADIATION INJURY AND LETHALITY 



to represent the non-recovering component. This presumption is based 

 on the following: 



1. The law of accumulation for this late branch is similar to that for 

 normal aging. 



2. The pathological findings are only quantitatively different from 

 those of age. 



3. Few physiological recovery mechanisms are known with time con- 

 stants of thousands of days, which might flatten it further (but see 

 above, p. 449). 



4. On genetic and cytological grounds, a non-recovering component is 

 expected to occur, and there is clinical evidence for it. 



The fact that injury appears to be non-recovering is, of course, no 

 reason for assuming that it is essentially irreversible, or that we cannot 

 influence it. On the contrary, the production of an analog of aging in 

 the laboratory enables us better to study the basic process of senescence 

 and the factors determining its apparent irreversibility. 



We inquire next whether there is experimental evidence to support the 

 hypothesis that radiation injury to physiological systems is a linear proc- 

 ess or, in other words, one which can be summated. There is some evi- 

 dence, but considerably more work in this line is needed. First, response 

 curves of certain physiological variables (as the responses of the vari- 

 ous types of leukoc3'tes) are linear in the sense that by a proper trans- 

 formation they can be brought into a form in which the responses con- 

 stitute a linear family of curves, that is, curves of the same form and 

 with amplitudes in the ratio of the doses (38). 



As to additivity of physiological responses we may consider the re- 

 sponse of a convenient variable (weight of growing rats) to single and 

 daily x-ray exposure (39). In Fig. 10 we show the response expressed 

 as the difference of logarithms of weights of control and treated groups. 

 This measure of effect can be rationalized in terms of a theory of cellular 

 growth. The single-dose growth response is similar to the derivative 

 of the daily-dose response, in so far as the time relations of phasic re- 

 sponses are concerned, but the single-dose response shows additional 

 components of effect which may be attributed to non-linear components 

 which arise when massive single doses are administered. One such com- 

 ponent, which can be shown to account for a considerable part of the 

 specific single-dose effect, is the transient anorexia which follows large 

 exposures. A second component, for which no quantitative data exist 

 under the experimental conditions employed here, but which has been 

 amply demonstrated in other situations, is that of cyto- and histo-archi- 

 tectonic disorder resulting from the rapid recovery following massive in- 

 jury. We may hope eventually to account for the observed irreversible 



