122 



activity was higher - minus 23 percent. 



Well now, you are faced with interpretation, and this poses some prob- 

 lems. 



BENNETT: I think before anyone tries to interpret such an experiment, 

 account has to be taken of the different rates at which these compounds will go 

 through the pools that you are discussing. It is very important in such an ex- 

 periment to know if the radioactive compound was present in the animal 2 hours, 

 24 hours, 4 days or whatever length of time. 



CARTER: And of course this information must be evaluated in the 

 light of the now well-established complexity of metabolic paths leading to nu- 

 cleic acid anythesis. If we take phosphorus, for instance, although many of the 

 intermediate steps between inorganic phosphorus and pentose phosphate may be 

 written, we don't know the mechanism whereby phosphate enters the polynucleo- 

 tide molecule. This uncertainty extends to the mechanism of pentose assimila- 

 tion. 



POTTER: You are absolutely right when you say that pathway is not 

 known. We have experiments showing that carbon 1 labeled glucose eventually 

 will get there, and it is hoped that some time in the next 10 years the pathway 

 might be known, but you cannot extrapolate from the studies on enzyme process- 

 es of which many alternatives occur in the animal. 



CARTER: In the case of the metabolic construction of the purine and 

 pyrimidine bases, the work of Greenberg, Buchanan and Kornberg has placed 

 us on sound ground. But to date, when we look at the studies of radiation ef- 

 fects on incorporation of low molecular weight precursors into nucleic acid, we 

 are unable to say whether inhibition or acceleration of the formation of the 

 purine and pyrimidine intermediates plays any role in radiation effects on nu- 

 cleic acid metabolism. This is asking for a lot of data, but whoever undertakes 

 to describe the effects of radiation upon nucleic acid metabolism must give us 

 a more complete statement about the fate of the precursor molecules. In the 

 case of radioactive formate, we need to know something about the effects of 

 radiation upon the complex that forms enzymatically between the 1 carbon unit 

 and the coenzyme form of tetrahydrofolic acid; we need to assess the experi- 

 mental findings on nucleic acid metabolism in terms of formate assimilation 

 into serine and protein as well as in terms of pool size and rates of excretion. 



Examination of the metabolism of some of these intermediates takes 

 on added importance in the light of some of the findings of Dr. Potter. He 

 isolated the pyrophosphates of all of the 5' nucleotides that occur in ribonucleic 

 acid and by this time probably has some that occur in the desoxynucleic acids. 

 It is tempting to believe that these compounds are the immediate precursors of 

 the nucleic acid. I say it is tempting because there is as yet no evidence that 

 proves it. 



POTTER: It is a matter of opinion, I guess. I think it is important 

 that in the first paper with Hurlbert, the quantitative yield from the acid soluble 

 pool to the acid insoluble pool is 80 percent or better. I will say that it is a 

 matter of opinion whether you say they must have been the precursors or not. 

 I don't think it adds anything to the discussion to go into it. 



CARTER: There is certainly no evidence from these experiments 

 that would argue against the 5' nucleotide being the precursor. 



