346 GENERAL DISCUSSION 



substance. Perhaps I might be allowed to say something here about the relation of 

 extracellular to mtraceUular changes. This morniiig it was suggested that possibly some 

 so-called extracellular changes might really be caused intraceUularly. This does not hold 

 anyway for the immediate effects seen during uradiation, they must be of extracellular 

 origin, and it does not hold either for the many things you can observe in dead tissues. 

 ALEXANDER: I wondcr whether Prof. Brinkman would like to make a guess as to whether 

 the immediate effects on the extracellular tissue of wliich he has just spoken have any 

 lasting influence — he's mentioned the fact that after two or three hours the damage 

 seems to have been repahed. Is it his guess that this recovery is incomplete and that 

 some of the permanent damage in connective tissue results from this, or are the permanent 

 changes in connective tissue due to the changes in the biochemistry and turnover of the 

 gromid substances? 



brinkman: That depends very much on what type of connective tissue you are con- 

 sidering. If it is the skin, I think that repair is complete, and that there is no residual 

 damage at aU. But if you consider the mucopolysaccharide and connective tissue fraction 

 in the aortic waU where they have an ultrafiltration function, breakdown of polymeriza- 

 tion for only 1 hour can be enough to let in macromolecules from the blood, and then you 

 have secondary consequences. 



BACQ: Cholesterol is not synthesized in the tissues of the blood vessels but mainly in the 

 liver. It is brought to the vessels by the blood from the liver, or from the food by intes- 

 tinal absorption. If one find an increased amount of cholesterol in a tissue other than the 

 liver (and the ach-enals) it means that for some time the capacity of tliis tissue for storing 

 cholesterol has been increased. I do not know if the various tissues of the blood vessels 

 metabolize cholesterol. 



BRINKMAN: I would Say that the ultrafilter layer of the wall of the large vessels is breaking 

 down all the time. It has already started with young children. You can see small plaques 

 especially round the places where other vessels join. It is a real struggle to keep the macro- 

 molecules out. This battle is lost if you add sufficient radiation. 



cottier: I just wanted to emphasize that tliere is quite a long latent period after irradia- 

 tion before these small vessel changes appear. This is somewhat hard to reconcile with 

 the assumption that the initial short-hved mcrease of permeability should be the main 

 factor responsible. I thuik that since the ground substance and fibrillar material is con- 

 tinuously renewed by cells, one should again emphasize that we need to know more about 

 the life-span of the endothelial cells and the function of these cells. 

 UPTON: I would simply Like to emphasize that we may be confronted by a midtiphcity of 

 effects. The initial effects on the ground substance fining the aorta may mdeed be 

 initiating events for the occurrence of atheromatous changes locaUy, which may or may 

 not be related to the changes in fine vasculature. 



Chromosome Breaks and Cell Death 



BACQ: I would Like now to call on Dr. MuUer, who wishes to make some comments as an 

 addition to his paper. 



MULLER: I thought I would give you an indication of how some of these matters that I 

 discussed with you yesterday might be checked quantitatively. I left the matter very 

 vague as to what proportion of cells were kiUed in a given case, but there are formulae 

 which Dr. Ostertag and I have worked out which should apply to this matter and which 

 we have put to a fittle testing. 



Suppose we have as a standard a chromosome of such length and other characteristics 

 that when it is subjected to a umt close of radiation, it has a certain effective breakabifity. 



