PHYSICAL AND BIOLOGICAL FACTORS 941 



a 5 per cent oxygen mixture for several minutes before and during irradia- 

 tion lowers the blood and tissue oxygen tension sufficiently to modify 

 free radical and peroxide formation to an appreciable degree. Mice are 

 also protected against lethal irradiation by anoxic anoxia (Dowdy et al., 

 1950). However, the range in which protection is evident is quite 

 narrow, protection being observed with 7 per cent but not with 10 per 

 cent oxygen, while a 5 per cent level is lethal during the period of irradia- 

 tion. As contrasted with these observations, the increase in chromosome 

 aberration frequency in Tradescantia is linear between and 10 per cent 

 oxygen, after which the rise is somewhat more gradual, tending to level 

 off above 20 per cent (Giles and Beatty, 1950). 



Several chemical procedures, which bear directly on the events associ- 

 ated with the oxygen effect, have been employed. Histotoxic anoxia pro- 

 duced by cyanide apparently increases the sensitivity of tumor tissue and 

 of Vicia faba to radiation (Crabtree and Cramer, 1933). On the other 

 hand, cyanide exerts some protective action against X rays in the mouse 

 (Bacq et al., 1950; Bacq, 1951), while it is without influence in the rat and 

 frog (Patt and Swift, 1948; Dowdy et al., 1950). Iodoacetic acid and 

 sodium fluoride which, like cyanide and oxygen deficiency, inhibit aerobic 

 glycolysis, do not affect the sensitivity of tumor cells (Crabtree and 

 Cramer, 1933). The failure of cyanide-induced anoxia to protect the 

 rat and the protection afforded this animal by anoxic anoxia have been 

 taken to indicate that radiation injury is related to the tissue oxygen 

 tension (Dowdy et al., 1950). On the other hand, it has been suggested 

 that cyanide may protect the mouse by inhibiting the formation of 

 peroxides by X rays and perhaps by forming a loose bond with certain 

 enzymes (cytochrome reductase and catalase) to prevent their oxidation 

 (Bacq et al., 1950; Bacq, 1951). The important species difference 

 between the mouse and the rat in regard to cyanide as well as its potentia- 

 tion of toxicity in plant and tumor tissue cannot be taken lightly. Poten- 

 tiation of tissue sensitivity by cyanide may be due to an increase in 

 oxygen tension as a consequence of inhibition of the cytochrome system 

 or to inactivation of catalase. Also unexplained is the finding that para- 

 aminopropiophenone enhances the resistance of mice and rats when it is 

 administered before X irradiation, while sodium nitrite, which produces a 

 rather similar methemoglobinemia, gives equivocal protection (Storer 

 and Coon, 1950; Herve et al, 1950). 



Chemical Protection. That oxidative reactions are important com- 

 ponents of radiation action is also suggested from studies with protective 

 substances. Thus, the in vitro oxidation of sulfhydryl enzymes following 

 low doses of radiation can be prevented or reversed by glutathione 

 (Barron et al., 1949), and radiation effects in tetanus toxin (Ephrati, 

 1948) and bacteria (Hollaender et al., 1951; Forssberg, 1950) can be 

 diminished by a variety of reducing substances. A number of oxidizable 



