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to expand so that the pressure falls below this minimum, it loses its activity 

 irreversibly. We argue that the decompression has permitted the unfolding of 

 the surface-spread proteins to the point where the specificity of configuration 

 that is responsible for its biochemical activity is lost. We can inactivate pep- 

 sin-albumin films with relatively low doses of X rays, when the films are at the 

 minimum pressure at which they are active. If now we compress the films and 

 test their sensitivity to X ray inactivation, we find that the sensitivity decreases 

 in a linear fashion as the pressure increases. Of course, we are decreasing 

 the area as we compress the film. In a sense, then, the "unfolding" of the film 

 results in an increase in radiation sensitivity. 



KAMEN: There is a great deal of evidence which suggests that the enzyme 

 is stablized by its prosthetic group and also by its substrates, so this is anoth- 

 er line of experimentation which opens up as a result of previous biochemical 

 studies. 



Another thing that occurs to me is that the state of enzymatic adaptation as 

 affected by radiation is still unexplored. Studies have been made, of course, 

 which show grossly that adaptation ceases when the cell is irradiated along with 

 other radiation sensitive processes. That is, if you knock out growth you also 

 knock out adaptation, but this is a crude way of going about it. There are ser- 

 ological techniques available which make it possible in principle to study the 

 protein composition of the cell during the adaptation process". If you want the 

 details, it is the work of Melvin Cohn and others (17), and while this is still in 

 the formative stage, it indicates that it is not going to be impossible to look for 

 precursor protein in the adaptive process. 



The question arises whether the adaptive enzyme is built entirely from 

 scratch or comes from a slightly modified precursor. So far it appears that in 

 the absence of external nitrogen sources the cell breaks down the other enzyme 

 completely and then builds the new enzyme from small units. The question is 

 at what stage of this process can one drag out the intermediates to see what they 

 look like. This is something for a combination of immunologists, biochemists, 

 and radiobiologists to look into. All I want to do is to bring to the attention of 

 this group the fact that this approach is feasible. 



We ought to have more specific information on just what molecules in the 

 biological system are expected to be sites for metastable states and, therefore, 

 for chemical action and what the chemical action is. It isn't just a matter of 

 saying you have chemical action. You ought to be able to say with some definite- 

 ness just what happens. 



I might just refer to experiments of Weiss and his group (18). They have 

 studied the effect of radiation of ultraviolet or X rays on the breakdown of de- 

 soxyribose nucleic acid at various dose rates and total dosage with different 

 radiations and also under different degrees of aeration. 



What they found, for instance, was that in the amino acid there was depoly- 

 merization and there was a fission of glycosidic links, liberation of free base, 

 deamination, breakage of ester rings, and splitting of the ribonucleotide link. 

 Everything in the molecule can be broken down by irradiation. So there must be 

 lost of sites for the localization of energy. Also, the reaction change involves 

 the whole molecule. Moreover they can change the ratio of these products by 

 irradiating either in hydrogen or oxygen. They find that the relative frequency 

 with which the phosphate is liberated from the phosphate part of the ribonculeo- 

 tide link increases as you increase the hydrogen concentration. 



