105 



cells that die or not. Finally, you have the problem of estimating whether the 

 death of some of the cells does not do something to alter the metabolism of the 

 cells that stay behind. 



Any susceptible tissue is going to have cell death after irradiation, and 

 unless you study radiosensitive tumors and radioresistant tumors, and a spec- 

 trum of tumors in between, where you can get a high degree of cell homogeneity. 

 I see no way to get around this problem. Even there I am not sure that you can. 



SPIEGELMAN: If you have very sensitive assay procedures for the 

 biochemical changes you are following, one way of deciding such a question is to 

 compare the answer you get from many small samples with a lumped sample. It 

 there is heterogeneity, it will show up very quickly. 



KAPLAN: I don't think the small samples would work. These various 

 kinds of cells are all interwoven in the same tissue. There are some geographic 

 relationships, with cortex and medulla in the thymus, and white and red pulp in 

 the spleen. But there is actually no proof, even within the white pulp, where 

 there are large lymphocytes and small lymphocytes and stem cells, that the me- 

 tabolism of each of these classes of cells is the same with respect to the things 

 that are being measured. So that in any tiny area of these organs, you are deal- 

 ing with different classes of cells. The problem in highly radiosensitive tissues, 

 if vou give a dose sufficient to get a measurable effect, is that some classes of 

 cells are simply not present in the early post-irradiation period. They are no 

 longer there to be sampled. 



POTTER: Would 15 minutes be soon enough? 



KAPLAN: There, of course, you are dealing with still another kind of 

 problem because some of the cells are in the process of dying. What you are 

 really asking is, what is the biochemical change that characterizes the cells that 

 have been hurt? Well, some of them have been hurt and are dying and others 

 apparently have not been hurt and may even have been stimulated to heightened 

 activity because of injury to the other cells present in the tissue. 



BENNETT: Do you feel that this difference in behavior depends on 

 their condition with regard to when they are going to undergo mitosis or anything 

 as general as that? 



KAPLAN: It apparently has nothing to do with it as far as lymphocytes 

 are concerned. 



POTTER: We cannot rule out these cells that are dying. I mean, it is 

 all right to talk about a change in composition, but presumably if we produce a 

 biochemical reaction which has something to do with their dying, then it is legit- 

 imate to look for that effect because that is part of the dying. 



KAPLAN: Yes, but you don't have any way of separating out the 

 changes that exist in the cells that are dying from the changes or lack of change 

 in the population that is not going to die. 



SPIEGELMAN: There is one technique that we have employed that may 

 or may not be applicable to this case. For example, we wanted to ascertain 

 whether during induced formation of enzymes all the cells of the population are 

 making enzymes uniformly or whether some are making a lot of enzymes fast, 

 and others very slowly. 



