196 G. W. CASAEETT 



Intensive highly-localized irradiation, as with internal radioisotopes which 

 concentrate in certain tissues, greatly enhances the tendency to diseases 

 related to the part irradiated, with relatively less enhancement of the tendency 

 to disease development in unrelated parts of the body. Whether we regard 

 these radiation-linlced diseases as induced or temporally advanced, the inci- 

 dence depends greatly on the latent periods for these diseases in relation to 

 the temporal proximity of development of other terminal diseases common to 

 the species or strain in other parts of the body. This, in turn, depends on the 

 age of the animal at the time of irradiation. 



In general, total-body life-shortenmg irradiation tends to increase the 

 incidence and/or the severity of age-dependent diseases at given chronological 

 ages (Blair, 1956; NAS-NRC, 1961; Furth et al, 1959; Casarett, 1952, 1956; 

 Upton, 1957; Alexander, 1957). One could perhaps assume that total-body 

 irradiation induces each of the diseases of advanced age separately. However, 

 it is more reasonable to regard such uniformity of response as a temporal 

 advancement of the diseases and as evidence that total-body irradiation 

 causes a nonspecific diffuse, subclinical deterioration of the body tissues that 

 advances the onset of many diseases to a roughly equal degree (Blair, 1956). 

 There are data which suggest that similar eifects may occur in man (Warren, 

 1956). 



SUBCLINICAL HISTOPATHOLOGY 



In general, the so-caUed diseases of agemg do not develop suddenly to 

 clinical proportions to be recognized as pathological entities, but are the 

 eventual results of slow, insidious, subclinical, deteriorations in tissues or 

 organs. The various specific terminal diseases which emerge are often only 

 more or less random expressions of more generalized tissue disorders. 



Agemg animal populations are seen by gross examination and by micro- 

 scopic examination to deteriorate slowly but generally in progressive fashion 

 before clinically or pathologically recognizable age-dependent disease entities 

 occur. These changes have been observed to occur prematurely followmg 

 irradiation (Casarett, 1952, 1956, 1957, 1958, 1960; Russ and Scott, 1939; 

 Henshaw, 1944; Jones, 1956). 



A fundamental ageing change in the adult animal may be defined as a 

 change which occurs consistently and progressively with the passage of time in 

 all temporally ageing individuals of the population, in the general phase of 

 life in which the change may be expected, and which is qualitatively inde- 

 pendent of variations in clinical history among individuals. Such a change may 

 be detectable initially at different chronological ages among individuals or 

 may vary quantitatively with disease history or variations in genetic con- 

 stitution or environment. 



