CONCEPT AND CRITERIA OF RADIOLOGIC AGEING 195 



instances that some of the diseases regarded as induced by the experimental 

 treatment under these circumstances may have been instead diseases of 

 relatively long latency with their time of onset greatly advanced temporally 

 in individuals with some propensity for them. 



The uivolvement of alteration of the ageing process in the effects of total- 

 body irradiation on life-span is often judged according to ideal standards and 

 assumptions which may not be true. Shortening of life by total-body irradia- 

 tion is conceded to be an effect of premature ageing only if there is no 

 induction of disease and if there is a proportionately equal temporal advance- 

 ment of all diseases common to the species or strain. In practice this ideal 

 concept impUes, among other assumptions, the assumptions that all of the 

 diseases in question are age-dependent to the same degree, that all of the 

 diseases and causes of death under conditions of maximal longevity are known, 

 that the irradiation is always applied uniformly throughout the tissues, and 

 that the irradiation, if it alters the degree, or rate, of ageing at all, must alter 

 the relative rates of ageing processes in various parts of the body to a degree 

 proportionate to their relative rates of ageing in non-treated animals. The 

 truth of this latter assimiption depends greatly on the fundamental nature of 

 the agemg process, which, of course, is not yet known. 



In the case of total-body irradiation experiments on rats and mice, some 

 experiments, especially among those with single dose exposures shortening 

 life with a simple temporal displacement of the survival curve, have shown 

 approximately the same diseases in approximately the same incidence in 

 irradiated and control groups (Blair, 1956), i.e. a simple temporal advance- 

 ment of disease. Other such experiments have shown similar results, about 

 the same diseases, although not necessarily in the same incidence. Still other 

 experiments have shown, in addition to advancement of specific diseases, a 

 considerable induction of certam other diseases. This induction tends to occur 

 more often in inbred strains with a high genetic susceptibility to certain 

 diseases, e.g. leukaemias or ovarian tumours in certain inbred strains of mice. 



The observed strain variation in life-shortening in irradiated mice can 

 be partially attributed to genetic differences in sensitivity to the leukae- 

 mogenic effects of irradiation (Grahn, 1958). When leukaemia mortality is 

 excluded, life-shortening due to all other causes is found to vary compara- 

 tively little between strains. 



Usually in the case of total-body irradiation of genetically more hetero- 

 geneous annual populations, the temporal advancement of disease is relatively 

 of greater importance in life-shortening than induction of disease; while, in 

 the case of highly localized irradiation, particularly with the use of the more 

 intense, or larger doses that it is possible to administer without acute lethality, 

 the induction of disease at the site of irradiation, or indirectly in a physio- 

 logically related site, is relatively of greater importance. 



