PHYSICAL AND BIOLOGICAL FACTORS 937 



the narrow range compatible with life is consistent with the concept of 

 indirect as well as of direct action since the free radicals must have zero or 

 nearly zero energies of activation. On the other hand, the events sub- 

 sequent to irradiation appear to be rate-sensitive ; yet, since recovery may 

 also be influenced, the ultimate outcome is not always changed. 



Consistent with these concepts are the findings that treatment of mice 

 with desiccated thyroid both before and after irradiation gives the same 

 enhanced effect as treatment begun after the exposure, while pretreatment 

 alone fails to modify lethality (W. W. Smith and F. Smith, 1951). It is 

 also noteworthy that survival is not altered by severe preirradiation 

 exercise (Patt, Blackford, et al., 1951) or by irradiating animals under 

 Nembutal anesthesia (Hempelmann et al., 1949; Patt, Blackford, et al., 

 1951). Although lethality is diminished when mice are given a heavy 

 dose of morphine before exposure to X rays, protection is probably a 

 consequence of the hypoxia resulting from depression of the respiratory 

 center (Kahn, 1951). In contrast, the lethal effect is augmented when 

 rats are anesthetized with urethane, a radiomimetic agent, and then 

 irradiated (Henry, 1949). This has not been observed in mice, however 

 (Paterson and Matthews, 1951). 



INTERMEDIARY RADIOCHEMICAL EVENTS 



The aberrations in cell chemistry that follow irradiation are not easily 

 resolved since the pathways of energy dissipation and the structure and 

 properties of biologically important molecules are still obscure. From 

 energy considerations and the widespread nature of radiation damage 

 there is reason to believe that the primary disturbance centers around 

 enzymes, genes, and other key molecules that are involved in the assembly 

 and synthesis of essential substrates. Presumably, certain of these 

 entities are inactivated or modified by direct ionization and excitation 

 and/or by the products of irradiated water. It has been postulated by 

 Barron (1946) and Barron and Dickman (1949) that the critically 

 involved enzymes are those requiring sulfhydryl groups for their activity 

 and that these are reversibly oxidized by low dosages and irreversibly 

 denatured by higher dosages. While sulfhydryl enzymes may be 

 inhibited by ionizing radiations under certain conditions, evidence for 

 their selective inhibition in vivo is incomplete (Dinning et al., 1950; 

 Dubois et al., 1950; LeMay, 1951). It is not known, moreover, 

 whether changes when observed are the cause or the effect of cell 

 injury and death. 



The abundance of water in biological materials and the demonstration 

 of activated water reactions in simple chemical systems have naturally 

 led to much speculation concerning their implication for radiobiology. 

 As stated by Weiss (1947), irradiated water is essentially an oxidation- 

 reduction system that consists primarily of free hydrogen atoms and 



