no 



significant biological effect. Or we can go to the cell surface and think of what 

 a few "holes" in the surface would mean for the function of the total cell. I am 

 thinking here of some of the things that Dr. Curtis has done on the possibility 

 of conduction from cell to cell. A few holes in the surface of a small cell 

 might mean the end of that cell -- would you agree, Dr. Curtis. 



CURTIS: Yes, that is true, but you have to think of repair processes. 

 You know that very large molecules can pass across cells. If you like, you can 

 say that they punch holes in the cell membrane that are repaired immediately. 

 It may be that they punch different kinds of holes than you are thinking about. 



MAZIA: I am not thinking of holes literally. I am thinking still of the 

 amplification problem. So much of our discussion of radiation effects deals 

 with them in terms of direct action of functional units such as enzymes. What I 

 am proposing for consideration are effects that alter the conditions of action 

 of the enzymes or other molecular units. Three of these have been brought up. 

 One is the case where a group of enzymes is clustered tightly in a functional 

 unit; if you knock out one, all others become useless. The second is where the 

 radiation action is not on the molecules at all but on the links -- or cement, if 

 you will -- holding them together in a functional cluster. The third is where the 

 environment is altered in a minor way which affects the activity of the large 

 molecules in a major way. An example of this would be a small change in the 

 surface of a cell or a nucleus or a mitochondrion, which, in turn, would permit 

 a small flux of some ion (H''" for instance) to which many of the molecules would 

 be sensitive. All of these effects are possible and all would be examples of am- 

 plification as long as we choose to relate the radiation exposure to its large- 

 scale physiologic consequences. 



KAPLAN: Especially the interrelationships of some of these large 

 structures in certain cells and not in others. That is a nonselective, irreversi- 

 ble damage to one molecule -- one or a very few molecules -- of such a large 

 structure could lead to inactivation biologically of the entire structure. 



That is a better thesis, I think, than the one that you started on tenta- 

 tively, which would force you to the notion that the radiation somehow could tell 

 which is the special, unique enzyme in the radiosensitive cells and pick it out 

 selectively, whereas it couldn't do this in any other cell. It seems more logical 

 to postulate that the radiation can nonselectively hit any kind of large molecule, 

 but that in certain kinds of cells there is a much more vulnerable interrelation- 

 ship between molecular structures. 



POLLARD: One of the things that has always affected me is the fact 

 that chromosome breaks are so easy to produce. When one thinks of a chromo- 

 some, it almost certainly consists of 50 or a 100 nucleic acid molecules lined 

 up alongside one another. It is often said, for example, that one a-particle 

 passing through this will cause a break. One a-particle may put a lot of energy 

 in there but actually does not put a 1:1 relationship in each of the molecules it 

 goes through. Perhaps an a-particle will, but a deuteron or a slow electron 

 won't. 



MAZIA: The situation with regard to chromosome breaks may not be 

 as difficult as it seems. I think that we are dealing with the dissociation of fair- 

 ly large nucleoprotein particles that are held together only by ionic bonds. The 

 structural stability of the chromosome maybe a little deceptive in the sense that 

 we usually encounter the chromosome under conditions where these bonds are 

 most effective. We have some evidence to support this. 



