308 Z. M. BACQ AND P. ALEXANDER 



action of radiation by cysteamine under conditions when disnlphide 

 exchange cannot occur. No evidence has ever been produced why these 

 other reactions ai'e not the ones that protect proteins in vivo. The only 

 reason for postulating that disnlphide exchange is related to protection 

 is that it is a reaction that occurs when cysteamine is injected into an 

 animal, but recent research (Betz and Lelievre, personal communica- 

 tion, 1960) indicates that there is no relation between the proportion 

 of cysteamine bound in the tissues and the importance of protection. 



The study of the mechanism of chemical protection in mammals is 

 complicated by several factors: (a) Cysteamine injected into the vein 

 or into the peritoneum is concentrated very unevenly by the tissues; 

 at the time when the injected animal is irradiated, the protector is 

 about 30 times more concentrated in bone-marrow, liver, spleen and 

 intestine than in the testis (Eldjarn and Nygaard, 1954; Verly et al., 

 1954; Verly 1955; Nelson and Ullberg, 1960). A large part of the activity 

 of cysteamine is probably due to the fact that it penetrates rapidly 

 within the cells of some critical organs (bone-marrow, liver, spleen, 

 intestine, hyjiophysis. (b) The oxygen jjressure in a normal man is high 

 in the skin, muscles and spleen, but low^ in the bone-marrow; in this 

 last tissue the oxygen tension is not increased (as it is in other tissues) 

 by breathing pure oxygen (Cater and Silver. 1960). Thus the oxygen 

 effect must be small in the bone-marrow although this tissue is knoAAii 

 to be very well protected in rodents by cysteamine and related sub- 

 stances. 



Eveiy tissue or organ within the mammal must be studied separately. 

 Several mechanisms may be active simultaneously and synergistically. 



Many authors (see for instance Gray e^aZ., 1952a, b) have suggested 

 that some protectors functioned by causing, via a pharmacological 

 pathway, the depletion of tissue oxygen. L. H. Gray (1960) also sub- 

 scribed to this view and suggested that the sulphydryl compounds re- 

 move oxygen by direct combination due to autoxidation which occurs 

 relatively rapidly under physiological conditions. 



Several methods may be used to exclude anoxia as the principal 

 mechanism of chemical protection in mammals. 



(a) The use of cystamine (the — S — S — oxidized compound related 

 to cysteamine) avoids the criticism of Gray and Scott. Many protective 

 effects of cysteamine have been duplicated with cystamine — but not 

 all of them. Careful study of the difference in tissue fixation, metabolism, 

 anoxiating effect, quality and intensity of protection, etc., between the 

 SH compound (cysteamine) and the S — S derivative (cystamine) 

 should be undertaken. 



(b) If the injected protector induces within the tissues a decreased 



