1000 RADIATION BIOLOGY 



Long-continued irradiation of adult bones by radium deposited in the 

 skeleton results in the appearance of areas of rarefaction and aseptic 

 bone necrosis, appearing late and progressing during the course of at 

 least 20 to 25 years. Necrosis is especially likely to occur in the jaw, 

 and the bone changes are precancerous (Martland, 1931). 



Although cartilage is not remarkably radiosensitive, its recovery after 

 irradiation to the point where necrosis occurs is very poor, perhaps owing 

 to vascular damage (Kaplan, 1949). Consequently, therapeutic irradia- 

 tion of cartilaginous areas, notably the ear and trachea, must be carried 

 out with great caution. 



METABOLISM AND TISSUE BREAKDOWN 



Metabolic changes may result from the direct action of radiation on 

 enzyme systems and other biochemical mechanisms, altered gastro- 

 intestinal, hormonal, and renal function, and the products of tissue 

 breakdown. Certain of the metabolic consequences of exposure to 

 X rays were described in 1907 by Edsall and Pemberton, who interpreted 

 clinical radiation sickness as a toxic reaction to tissue breakdown. Intox- 

 ication was attributed to the inability of the organism to metabolize and 

 excrete the products of cellular disintegration. Subsequently, Doub 

 et al. (1925) observed a hyperphosphatemia that was related to radiation 

 dosage, and noted, in addition, that irradiation of large tumor masses 

 resulted in an early alkalosis and elevated blood levels of nonprotein 

 nitrogen, uric acid, and guanidine. Arguments in favor of the tissue 

 toxin hypothesis have been advanced by a number of investigators since 

 the early work of Edsall and Pemberton (Hall and Whipple, 1919; 

 Stafford L. Warren and Whipple, 1923d; Rolleston, 1930; Forfota and 

 Karady, 1937; Moon et al., 1941). It is quite possible that tissue break- 

 down products contribute to the early shock reactions with massive 

 irradiation. Their role with smaller dosages is not well defined, although 

 there is some evidence that circulating factors may be involved in the 

 initial toxicity resulting from such exposures (Barnes and Furth, 1943; 

 Painter et al., 1947 ; Weber and Steggerda, 1949 ; Ellinger, 1951). Toxins 

 may, of course, be expected in the presence of the bacteremia that occurs 



later. 



Metabolic changes attributable to protein breakdown are also apparent 

 from some of the more recent studies with deep roentgen therapy in man 

 and with experimental irradiation of animals (Goldman, 1943; Robertson, 

 1943; Prosser et al., 1947a, b). Urinary nitrogen is increased during the 

 first hours after irradiation, and specific organ proteinases have been 

 detected in the urine of the dog (Oster and Salter, 1938; Abderhalden, 

 1939). The subsequent excretion of nitrogen is usually maintained 

 within normal limits until shortly before death. Since intake is reduced 



