78 



MAZIA: You hit DNA synthesis -- 



CARTER: If this is going to be our working formulation, could we get 

 Tobias to state his idea again, because this is going to dominate radiobiology for 

 a long time and we should have it clear? 



MAZIA: Perhaps we should finish with Dr. Spiegelman's question. We 

 think that you hit DNA to cause the delay in division, but that cytoplasmic mech- 

 anisms are responsible for the reversal of the radiation effect. We took photo- 

 graphs with the ultraviolet microscope at 2537 % to see whether there was total 

 absorption, in which case the difference between the whole cell and the half cell 

 might be accounted for by shielding of the nucleus. We concluded that we didn't 

 have total absorption because neither photograph was black. In fact, there 

 wasn't much difference; the ameba cooperates by flattening out. 



KAPLAN: I am not sure that I understand the suggested mechanism that 

 activates mitosis in the nucleus. Is the idea that the piling up of RNA is the trig- 

 ger mechanism? 



CARTER: Could we get a clear statement of this again? 



TOBIAS: I will try to state it again, but I hope you will take these ideas 

 as mere suggestions and speculation without proof. Dr. Mazia made two asser- 

 tions- (1) that a certain amount of RNA has to build up in a cell before a cell will 

 divide and (2) that DNA is responsible for the synthesis of RNA. Irradiation 

 with a sublethal dose might affect the amount of RNA or the ability of RNA to 

 have its normal biochemical function. DNA, or if I may go farther, the genes ot 

 the cell, are not materially affected; if they were then we would have a lethal 

 effect instead of mere cell division delay. 



Now the cell would like to divide, but part of its RNA is inactivated and 

 it is necessary for the DNA to synthesize some new RNA, so cell division can be 

 triggered. This will take time, however, and a cell division delay occurs. 



There is other corollary information on the role of RNA in radiation 

 damage. Already it was pointed out by Kaplan that RNA actually increases in the 

 post-irradiation period. 



At higher lethal doses this model would admit damage to the DNA mole- 

 cules or to their ability to duplicate themselves. 



Does the model sound plausible to you. Dr. Mazia? 



MAZIA: Yes. But again we have to distinguish between two facts about 

 DNA DNA has to double before division in order to provide each daughter cell 

 with a full diploid complement. But it does not have to double in order to do its 

 normal iob in the cell. Theoretically, you could have a situation in a radiation 

 experiment in which you blocked division because you blocked the formation of 

 new DNA, but did not necessarily affect RNA formation because you had not dam- 

 aged the DNA that was already present. 



SPIEGELMAN: Are you postulating a permanent involvement of DNA in 

 the formation of every RNA molecule? 



MAZIA: No. 



POTTER: Spiegelman can probably think of other limitation. I am 



