PHYSICAL AND BIOLOGICAL FACTORS 939 



an increase in intracellular water following lethal irradiation of the whole 

 animal (Soberman et al., 1951). While dehydration may decrease radio- 

 sensitivity by minimizing cell swelling, a more likely explanation seems 

 to be the interference with activated-water reactions either as a result of 

 a decrease in the available water or an increase in the concentration of 

 protective substances. The dependence of sensitivity on the degree of 

 hydration has been demonstrated in seeds (Petry, 1922), seedlings (Hen- 

 shaw and Francis, 1935; Wertz, 1940), isolated tissues (Chambers, 1941), 

 and tumor cells (Failla, 1940). Yet it has been difficult to determine 

 whether this relation holds in the intact animal. Mice deprived of water 

 for 24 to 40 hours before X irradiation tend to live somewhat longer, but 

 the proportion surviving is not altered materially (France, 1946). Frogs 

 kept in dry, individual containers for 3 days lose about 35 per cent of their 

 water, yet are no more resistant to irradiation (Patt and Tyree, unpub- 

 lished observations, 1949). Even though appreciable water remains, 

 some quantitative difference at this level of dehydration should be 

 anticipated. Perhaps the answer lies in the relative concentrations and 

 distributions of free and bound water under these conditions of water 

 deprivation. 



Hydrogen Ion Concentration. The local changes in pH that probably 

 occur in the neighborhood of an ion track may play a role in the develop- 

 ment of radiation injury. The formation of hydrogen peroxide has been 

 shown to depend upon the hydrogen ion concentration, and changes in 

 pH have been observed in irradiated solutions (Frilley, 1947). Varia- 

 tion in pH during irradiation alters the radiosensitivity of germinating 

 fern spores, Drosophila eggs, and paramecia, sensitivity maxima being 

 observed at definite concentrations of acid or base (Zirkle, 1936, 1940, 

 1941). Zirkle has compared this behavior with the effect of irradiation 

 on proteins in vitro, where maximal flocculation is observed at a pH near 

 the isoelectric point. This is considered to be consistent with the 

 hypothesis that total sensitivity is due to the added effects of several 

 reactions having maximum yields at different acidities. There is little 

 information in connection with pH effects in isolated mammalian tissue 

 or in the whole mammalian organism. Change in the pH of thymic cell 

 suspensions from 7.8 to 6.6 does not influence the action of X rays 

 (Schrek, 1946). 



Oxygen Effects. The effect of ischemia on cutaneous radiosensitivity 

 was observed by Schwarz in 1909. The relative resistance of Ascaris 

 eggs during anaerobiosis was described subsequently by Holthusen (1921), 

 who attributed the protection to the absence of cell division. Several 

 years later Mottram (1924) and Jolly (1924) investigated the effect of 

 blood flow on the response of skin and lymphatic tissue to X rays, and in 

 1933 Crabtree and Cramer presented a detailed account of the influence 

 of anoxia and related chemical factors on the radiosensitivity of tumor 



