126 



pools that have decreased and other pool sizes that have increased after irradia- 

 tion. 



CARTER: Or some nucleic acids that turn over more rapidly or some 

 areas of the molecule that exchange rapidly. It is conceivable, for instance, that 

 formate may exchange into the thymine moiety without net synthesis of the mole- 

 cule. 



I think the other problem that we must consider here is the effect of 

 radiation upon structure and how structure may influence the expression of ac- 

 tivity. In all of these discussions of structure we can only go so far as informa- 

 tion of the kind that Chargaff and Cohn have provided is complete, and I don't 

 believe that even they will admit that it is complete. But nevertheless it is upon 

 our fundamental knowledge of structure that we must proceed in these analyses. 



The effect of radiation upon the biological activity of nucleic acids may 

 be due to a disruption of structure in the high molecular weight compound as well 

 as to failure of its synthesis, and that disruption of structure is expressed in 

 subsequent reactions. So that I don't believe that we should consider synthesis 

 and turnover to the exclusion of structural factors. 



PLATZMAN: You said, "may be due to disruption of the structure. " 

 What are the alternatives? 



CARTER: Well, the structure of the enzymes and the structure of the 

 co-factors in the system, etc. , that are not related to the high molecular weight 

 structure of the nucleic acid. 



PLATZMAN: It must be some structure? 



CARTER: Yes, I don't believe in ethers. I am trying to separate the 

 events. The point I want to make is that this transforming principle, disrupted 

 by ionizing radiation so that it looses its activity, will have the net expression 

 of failure of synthesis, but that the immediate event may be that which takes 

 place on this high molecular weight structure, completely independent of the 

 enzymes, the coenzymes, and the low molecular weight substrates that go into 

 the constitution of the newly synthesized compounds. 



The effects of ionizing radiation upon structure that have been de- 

 scribed fall into two categories. There is the fry-and-fall-back school of 

 radiobiochemistry where many roentgens are dissipated into solutions contain- 

 ing solutes of biological interest. Then there are the studies done at relatively 

 low absorption of energy in solution. I believe that both of these approaches 

 give interesting and valuable information. 



I don't believe that the fact that it takes a lot of energy to produce 

 certain detectible changes in the structure of the nucleic acids argues against 

 this being important or an event that is involved in radiobiological response. I 

 think that in a suitable system with suitable amplification such as Dr. Pollard 

 talks about, and with the use of suitable enhancement factors, such as Dr. Bar- 

 ron has demonstrated, it may take place. Scholes and Weiss(^) and Butler and 

 Conway(5) have recently, at least, done most in this area and they have shown 

 that there is actual disruption of the high molecular weight structures with high 

 dosage of irradiation; even the heterocyclic rings break. 



CHARGAFF: Is there evidence in this approach that the nucleic acids 



