102 



changes in the enzyme itself, secondary to some other change within the radio- 

 sensitive tissue or the result of injury to some other tissue. 



I think that it is necessary to continue a systematic investigation of var- 

 ious enzyme systems so that we can perhaps eventually arrive at a definition of 

 radiation damage in terms of certain biochemical pathways. 



CURTIS: I gather you feel that there is a certain amount of hope that 

 biochemistry will eventually find one key enzyme that is hit by radiation. Or, do 

 you feel that this approach has been pretty well worked over and it is time to try 

 other approaches such as the precursors of the enzymes or DNA or something of 

 that sort. 



DUBOIS: I feel that both approaches should be pursued with equal vigor. 

 I don't think that the DNA aspect should be studied to the exclusion of the one 

 under discussion. I feel that the enzyme changes precede the cellular changes, 

 but at the present time, we are not far enougn along to say that there is any con- 

 clusive evidence in support of this opinion. 



CARTER: Does not your work actually tend to show that it is not the 

 enzyme but the tissue that is specifically sensitive? That is, liver certainly has 

 5-nucleotidase, heart has and spleen has, but the spleen manifests its sensitivity 

 to radiation by increasing the apparent activity of this enzyme. 



DUBOIS: Yes, the work certainly shows the difference in tissue sus- 

 ceptibility. Although enzymes with similar catalytic properties exist in the re- 

 sistant tissues they may differ markedly in their susceptibility to poisons. Nat- 

 urally occurring protective substances, differences in requirements for activa- 

 tors, and even differences in their chemical constitution cause enzymes in vari- 

 ous tissues to respond differently to toxic agents. Thus, concluding that proteins 

 which catalyze a particular reaction in all tissues should be affected similarly by 

 a toxic material is not necessarily a valid conclusion. 



PATT: I quite agree with Dr. Carter and have very little to add except 

 to re-emphasize that even if one can relate a change in a particular enzyme to 

 subsequent changes in the cell population, this may still be a rather indirect 

 manifestation of the initial biochemical injury. In other words, this enzyme need 

 not necessarily represent the immediate locus of radiation action. 



SPIEGELMAN: In what cases can you relate any changes to the killing 

 of cells? 



PATT: Massive X irradiation, e.g., 50, 000 r, can embarrass respi- 

 ration of liver and kidney or of avian red cells in vitro , presumably because a 

 certain number of cells have been killed. 



SPIEGELMAN: That is many times the lethal dose. 



PATT: Yes, in terms of the whole animal. In general, it takes a 

 rather large exposure to embarrass respiration. 



BARRON: But DuBois has shown that he can inhibit the respiration of 

 the spleen. 



SPIEGELMAN: It seems to me that this does not mean that the radia- 

 tion did anything to the enzyme because he looked at them a long time afterward. 

 It must be a secondary response to some other event. 



