104 



what goes on in these tissues may eventually come back to some of these com- 

 mon denominators between nucleotide metabolism and nucleic acid synthesis. 



Regarding Dr. Patt's and Dr. Carter's comments, I should like to say, 

 that this may be a matter of tissue damage and that I think the same enzyme can 

 be knocked out by X irradiation in all of the tissues. The reason you have sen- 

 sitive tissues is simply because those tissues contain less of the enzyme that is 

 hit by the radiation and that the effect that Dr. DuBois sees is the reflection of 

 the knockout of that enzyme present in such small amounts. 



We have examples in our own experience where the enzymes in the 

 various tissues can be shown to be susceptible to highly specific agents, and 

 when you hit the whole animal with these agents, some tissues are not affected 

 at all. They are the ones that have large amounts. 



PATT: Is there any way of increasing the concentration of these en- 

 zymes other than with irradiation? It should be possible then to test this hypoth- 

 esis by irradiating at a time when the levels are already increased. 



POTTER: While this discussion is on pi-otection against X irradiation, 

 I should like to ask what you can add that potentiates irradiation. 



PATT: High oxygen tensions may enhance effects on tissues that are 

 ordinarily somewhat anoxic but oxygen will not effect enhancement generally. 



PLATZMAN: Has pure oxygen ever been tried? 



PATT: Pure oxygen does not alter the sensitivity of animals as judged 

 by lethal effects. Returning to Dr. Potter's question, certain agents, e.g., 

 nitrogen mustards, can synergize with X-rays but the effects are complex. One 

 can potentiate or enhance the killing of animals by imposing a variety of stresses 

 or traumas but I think these may be very far removed from the sort of reactions 

 that we are thinking about here. 



TOBIAS: Hypophysectomy prevents formation of some enzymes, and 

 it is known that many hypophysectomized animals are more radiosensitive also. 

 Should one use hypophysectomized animals to study enzyme activity? 



KAPLAN: We have data that indicates that hypophysectomized animals 

 are not appreciably more radiosensitive, at least in terms of lymphoid tissue 

 response. I think you have to admit that a number of these animals are so mark- 

 edly starved to start with that the increment that one gains after irradiation is a 

 rather meaningless increase in mortality that you would get if you half-killed 

 them with any other agent. 



PATT: We studied hypophysectomized rats some years ago and also 

 observed an increased sensitivity to lethal action but not to atrophy of lymphoid 

 tissue. 



KAPLAN: I have been thinking about trying to find some experimental 

 way to get around this problem of cellular selection in a radiosensitive tissue 

 with respect to biochemical determination at some interval following irradiation. 

 You really have several possibilities. When you irradiate a radiosensitive tis- 

 sue, a lot of cells die. The first question is to what extent are the biochemical 

 changes that you see, a reflection of alterations in the cells that die? The sec- 

 ond question is that there are cells that are left behind. You really don't have 

 any way of knowing whether their initial biochemistry is the same as that of the 



