PHYSIOLOGY OF RADIATION INJURY 983 



550 to 1100 r. Effects on radiation morbidity and mortality have also 

 been demonstrated by Jacobson and his associates (Jacobson, Marks, 

 Robson, et al., 1949; Jacobson, Simmons, et al., 1950) with spleen shielding 

 of an otherwise totally irradiated mouse. Even in the median lethal 

 dosage range, however, mortality has been shown to be related in time 

 to a bacteremia of intestinal origin (Miller et al., 1950b), and it is perhaps 

 significant that maximal damage to the crypt epithelium precedes the 

 peak mortality of chronically irradiated mice (Bloom, 1950). 



Qualitatively similar effects on the gastrointestinal tract have been 

 observed in a number of species after exposure to penetrating radiations 

 or to internally administered radioisotopes (Friedman, 1942; Desjardins, 

 1931a, b, c; Lawrence and Tennant, 1937; Pierce, 1948). The most 

 impressive changes occur in the epithelial cells, although the reactions 

 are not confined to them. Lesions have been noted during the first 

 hour after irradiation (Pierce, 1948; Tsuzuki, 1926; Friedman, 1945). 

 While it is generally agreed that the crypt epithelium is the most sensitive 

 site, destruction of the entire intestinal lining can occur with lethal dos- 

 ages, leaving fragmented crypt cells, denuded villi, edema, hemorrhage, 

 and ulcers in its wake. A marked accumulation of bacteria is often seen 

 on the surface of the intestinal mucosa. In contrast, nuclear injury in 

 the colon and in the surface epithelium of the stomach is usually slight, 

 although the gastric glands are rather easily damaged. The patho- 

 logical physiology does not always reflect morphological injury. The 

 occurrence of severe diarrhea, for example, may be unrelated temporally 

 to histological changes in the intestine (Shields Warren, MacMillan, and 

 Dixon, 1950a, b). 



As might be anticipated, intestinal damage is influenced by the rate as 

 well as the intensity of exposure, injury of the crypt epithelium and the 

 production of ulcers being decreased with fractionation (Stafford L. 

 Warren and Whipple, 1923b; Engelstad, 1935, 1938). Indeed, some 

 radioresistance of the crypt epithelium may be acquired with suitably 

 spaced small exposures (Bloom, 1950). No doubt, much of the variance 

 in the early investigations can be attributed to differences in the physical 

 conditions of irradiation. 



The causal relation between irradiation and morphological injury is 

 poorly understood. Nucleic acid, protein, and ash content of the crypt 

 epithelium is decreased soon after neutron and X irradiation (Ely and 

 Ross, 1948a, b; Ross and Ely, 1949a). Although the rates of synthesis 

 of DNA and RNA in rat intestine and in rabbit intestine are markedly 

 reduced by X rays, protein synthesis is relatively unaffected (Abrams, 

 1951). Alkaline phosphatase activity of the crypt cells is essentially 

 normal when assays are carried out at pH 7; phosphatase activity is 

 increased, however, at pH 9 (Ross and Ely, 1949b). It is not known 

 whether these chemical changes are the cause or effect of morphological 



