101 



PATT: I think the prevailing evidence indicates that the PAPP prob- 

 ably works through an anoxic type of effect. 



SPIEGELMAN: Can you get the same effect by choking the animal? 



PATT: I am sure that you could. Some years ago, Titus Evans 

 strapped the chests of young rats to mechanically retard breathing and he ob- 

 served certain protective effects. As I recall Storer and Coons' original work, 

 the maximal methemoglobinemia occured at about 30 to 45 minutes after injec- 

 tion; yet apparently the maximal protective effect occurred when the material 

 was injected immediately before irradiation. This is the only fact I am aware 

 of that does not quite jibe with a resolution in terms of anoxia, although I think 

 that it is due to anoxia. 



DUBOIS: Since their animals were irradiated for a period of approxi- 

 mately 20 minutes, it is possible the effective methemoglobinemia was achieved 

 during the middle of the radiation period. 



BENNETT: This would affect the LD50 by a factor of only 50 percent. 

 It is not a major effect, though. 



DUBOIS: The effect of this prophylactic agent on ATP-ase was to re- 

 duce the amount of rise in enzyme activity after 800 r to a level that would have 

 been seen after 200 to 400 r in the unprotected animal. 



As a practical use of this particular finding, one can employ this rela- 

 tively sinnple assay system to screen potential prophylactic or therapeutic 

 agents. 



KAPLAN: Is this actually cheaper than weighing the tissues or getting 

 histological sections? 



DUBOIS: No, it would not be advantageous if one could get results 

 with a few animals by weighing the organs, or if the difference between 400 and 

 600 r at 24 hours could be detected by organ weights. However, we do not feel 

 that organ weights are that reliable, and a larger number of animals are needed. 

 Therefore, enzyme assay has been a faster method and more reliable with fewer 

 animals, at least in our experience. 



Mercaptoethylamine and cysteine also protect against the increase in 

 nucleotidase activity of the spleen after 400 r. Nearly equal protective effects 

 were obtained with mercaptoethylamine at the maximum tolerated dose which is 

 175 mg. per kg. and with cysteine at 1000 nng. per kg. given I. P. I think this 

 agrees with Dr. Patt's mortality findings with these agents. Again we have here 

 a demonstration of two agents that will protect against a biochemical change in- 

 duced in the spleen by radiation and will also protect against radiation mortality. 



In connection with the problem of the biochemical mechanism of radia- 

 tion damage, I have mentioned some of the experiments that have been done to 

 point out progress that has been made and areas that need study. I think it has 

 probably become apparent that ionizing radiations do not produce widespread in- 

 hibition of enzyme reactions in living animals and that a great many of the im- 

 portant reactions in intermediary metabolism go unharmed after relatively large 

 doses of radiation. Furthermore, the larger effects that have been obtained are 

 noted only in the so-called radiosensitive tissues and even there, a great deal of 

 work is needed, as several discussants have pointed out, to show definitely 

 whether these are primary effects in the sense that they are radiation-induced 



