36 Discussion 



Alexander: I think we should differentiate between lyophobic colloids, 

 which are essentially unstable colloids which will aggregate in time, and 

 solutions of macromolecules with which one deals in serum albumin 

 which is stable. The reason why I mentioned the physical changes in 

 proteins produced by radiation is that they can play a part in removing 

 the enzyme from its sphere of action and this may be as serious to the 

 cell as true inactivation. Aggregation induced by radiation is very 

 dependent on the conditions of irradiation and may contribute to the 

 variation in the radiosensitivity of cells with changing conditions. 



Dale: This is a useful suggestion. 



Popjak: I would like to raise a question about our general way of 

 thinking about effects of radiation on enzymes. I suppose the reason 

 why most people are looking for inactivation of enzymes really springs 

 from the overall effects observed, i.e. that the radiation eventually kills 

 an animal or a cell. Now, are we right in assuming that radiation will 

 necessarily inactivate an enzyme? The biological effects that are ob- 

 served are observed with relatively small doses; how far is one justified 

 in concluding from the irradiation in vitro with very large doses of a 

 crystalline enzyme, divorced from its substrates and all its other com- 

 panions, that the same sort of phenomenon is operating in the cell? 

 When an enzyme is inside the cell it is working fairly fast, and there is 

 a continuous movement of electrons and protons in and around the 

 molecule probably forming some kind of resonating system. I wonder 

 whether we might not by irradiation change enzyme specificity, change 

 rates of reactions, and whether it might not be worth while directing 

 some work towards that end rather than watching the enzyme in- 

 activation, and whether more information as to biological effects might 

 not be obtained in this way. 



Dale: This is just what I had in mind when I put those questions at 

 the end of my presentation. My point of view is that it is quite possible 

 that a very minute functional part is changed while it is in transit and 

 that small changes may upset the proper sequence of events, changes 

 which may be so small that they are not analytically detectable, but 

 whilst the reaction is going on in the cell it may be of much greater 

 significance than the depletion of absolute amounts of enzyme. If, for 

 instance, in the enzymic reaction the functional part is slowed down it 

 cannot provide precursors for another reaction at the right time, so 

 that the integration of various interdependent reactions is destroyed 

 and, in my opinion, any attempt at trying to find a difference in enzyme 

 content of irradiated tissues or cells or disintegrated cells is, from the 

 start, completely futile because you only catch the total amount of 

 enzyme which does not matter at all. We are quite agreed that radiation 

 can only deal with a minute fraction of the enzyme present, but it all 

 depends on whether this minute fraction in the circumstances in which 

 it works in the cell is not relevant to the effect and, of course, from the 

 practical point of view it is very difficult to find experimental conditions 

 for checking what you suggested. 



Butler: I would like to support Popjak's view on these grounds: you 

 have two classes of enzymes, those that are present in the cell in quite 



