336 H. A. Blair 



chronic data will have no exact counterpart in recovery measured directly by test 

 doses. 



According to the hypotheses, recovery should not exceed the irreversible 

 component ay/. The data confirm that at least after some months following 

 exposure the irreversible component is demonstrable as a decrease of LD50 

 and it is ultimately demonstrable as a decrease in life span. Nevertheless, 

 there are some data on recovery showing that in the first few weeks test doses 

 for lethality may attain or even exceed values for animals not previously 

 irradiated. The natural conclusion from these data is that recovery may be 

 complete or even more than complete in that an apparent tolerance to radiation 

 is developed. Owing to a number of factors, the nature of this apparent transient 

 complete or over-recovery is not clear. One of the factors is that if the experi- 

 ments are done on young animals which have not attained maximal LD50 

 (Fig. 2), increase of LD5Q during recovery will obviously make recovery appear 

 greater than it really is. This defect may not be obviated by comparison with 

 controls at each stage of the experiment, because LD50 may increase differently 

 with age in the irradiated and control groups. 



Another disturbing factor is that fast recovery of the abdominal region 

 will make the earlier part of the recovery curve fall faster than is appropriate 

 to the remainder of the body and the later part of the recovery curve will be 

 lower, because, after the abdomen has recovered considerably, the dose required 

 to kill will be greater than it would be if the whole body were recovering together. 

 This factor will tend to obscure an irreversible remainder until all recovery 

 has proceeded as far as it will. 



Another possibility is that the animal may develop a transient physiological 

 reaction to acute radiation injury which temporarily raises the lethal threshold 

 for a second dose. 



For all these reasons the irreversibility of radiation injury probably cannot 

 be evaluated properly until at least several weeks after a substantial dose 



The question of whether parameters in biological systems are age dependent 

 should always be raised. In the case of recovery, for the reasons given above, 

 evaluation of the constants or constant ^ is difficult by direct measurement. 

 Nevertheless if the unanalysed recovery curve itself is similar at different ages 

 this is an indication that the constants have not varied. Hursh and Casarett 

 (13) have shown in the rat that the recovery curve at 546 days (beyond middle 

 age) is similar to that at 107 days (young adult). More study should be given 

 this problem, but at present there is no indication that the rate of recovery 

 is age-dependent. 



The problems of whether irreversible injury is the same per unit injury 

 at all ages, whether it slowly diminishes or increases, whether it gives rise to 

 shortening of life because it is identical with ordinary aging or because it 

 promotes ordinary aging, and whether it can be altered in any way, once laid 

 down, are of considerable interest with respect to the setting of permissible 

 levels for human exposure. If, for example, the irreversibility of radiation 

 injury could be reduced the consequences of exposure would be reduced 

 similarly. 



Referring to Fig. 3 the indications at present, though far from complete, 

 suggest that irreversible injury once laid down remains at constant level, 



