THE RESPONSE OF TISSUES TO CONTINUOUS IRRADIATION 219 



muller: I found this very enlightening also, but also a bit puzzling because, although of 

 course I accept it — it seems to me to run counter to the principle which was put forward 

 something lilce 60 years ago by Bergonie and Tribondeau, and received a lot of support 

 from different sides, that is, that tissues which divide rapidly are themselves more injured 

 by radiation. This can be understood on genetic grounds, but perhaps there is some way 

 to reconcile it because I think, in addition to that principle, we also have to remember 

 that there are also selection processes taking place so that injured cells tend to be replaced 

 by cells which are not so injured. As a result there is a kind of balance of one of these 

 processes against the other to give the final result. For difi"erent tissues that balance 

 might well be different. 



LAMERTON: Yes, Dr. Muller, but I beheve Bergonie and Tribondeau based their con- 

 clusions on the work of Regaud with the testis of the ram. In the testis you have apparently 

 very little feed-back and this, I suggest, is why the testis is so susceptible to continuous 

 radiation — there you can see the results of the injuries and they are not masked by any 

 subsequent rapid regeneration. If the early workers had looked at the epithelium of the 

 small intestine they might have come to another conclusion because there the immediate 

 effects of radiation can so easily be masked by the results of rapid regeneration. 

 DRASiL: I would like to ask two questions with regard to the adaptation in the intestine 

 to which you were referring. Firstly, could it be some kind of selection of more resistant 

 cells originally present in small numbers? Secondly, have you done more detailed cy to- 

 logical exammations to show increasing chromosome numbers after irradiation? 

 lamerton: With regard to the first pomt, the problem about selection is that the 

 increased radioresistance, if it be such, seems to come on rather too quickly. However we 

 did consider the possibility of polyploidy developing and this was supported by the fact 

 that the uptake of tritiated thymidme per ceU m the contmuously irradiated animals 

 doubled or trebled very quickly. Dr. Kember, working with Dr. Quastler at Brookhaven, 

 did a cytophotometric study but found no evidence of increasing ploidy and we have now 

 come to the conclusion on other evidence that the increase m tritiated thymidine uptake 

 is due to an availability difference rather than to any cliromosomal difference. It may be 

 due to some sort of selection but if so, then it would appear to happen very quickly. 



There is still one other possibility and this is that a tissue which is regenerating at an 

 abnormal rate may not be the same, biochemically speakmg, as normal tissue — I mean, 

 for instance, you may have anoxia or some other factor. 



To return for a moment to your second question about chromosome studies. Dr. 

 Wimber of Brookhaven, who was working with us for a year, did examine the bone- 

 marrow of animals which had been exposed to continuous irradiation at 50 rads per day 

 for 100 days but he found very little evidence of chromosomal abnormalities m these 

 animals. 



BRINE3IAN: I should like to ask if the rapid increase in radioresistance in the gut cells 

 could be explained by the liberation of serotonin from these regions. 

 lamerton: It may indeed. At the moment we have no satisfactory explanation and this 

 is certainly a possibihty. 



DEVIK: Do you thmk there could be any correlation between the dose given to the ceU 

 during one ceU cycle? Do you find that there is a critical dose delivered during one cell 

 cycle? It might appear to be so from the curve you showed. 



LAMERTON: WcU, in order to study this, one wants to look at cells of difi'erent generation 

 times. We are not sure about the generation times of the bone-marrow cells, one of the 

 problems being that we have such a complex system. What we are still hoping is that with 

 the gut we shall find cells of different generation times and be able to compare their 

 response though I think it is very unreasonable to beheve that sensitivity to continuous 

 radiation Mill increase indefinitely with the length of the cell generation time. 



