121 



cleic acid precursors will be those that describe most completely the fate of the 

 precursor after it is administered to the animal, not only m terms of nucleic 

 acid metabolism but into other metabolic areas as well. And I think in assess- 

 ine nucleic acid metabolism with these techniques, those experiments that em- 

 ploy several different labeled precursors - precursors of the heterocyclic ring 

 structure,, e.g. , ribose and phosphorus, will be of greatest value. 



There is a large body of literature on the effect of radiation on incorpo- 

 ration of isotopic precursors into nucleic acids. I am not S^^^g .^ wTrHnaton 

 review it I am going to introduce some of the evidence gathered by Harrington 

 Ind Lavik(l) 3,nd%se that as a starting point for this discussion. This evidence 

 is based upon experiments in which rats were given 100 r of x irradia ion. 

 Soon after the exposure the labeled precursor was given. After an interval, 1 

 believe it was 24 hours in these cases, the thymus gland was removed. Ihe 

 desoxynucleic acid molecule was degraded, and the incorporation of activity into 

 the various fragments was determined. They assumed that the precursor given 

 to the animal was the precursor of the high molecular weight nucleic acid And 

 they expressed results in terms of a ratio of the molar specific activity of the 

 isolated compound and the administered precursor. 



All the factors that we discussed briefly, of course, have to be taken 

 into consideration in the interpretation of the results. But some interesting 

 data emerge from an experiment of this type. 



TABLE I 



EFFECT OF X IRRADIATION ON INCORPORATION OF 

 RADIOACTIVE PRECURSORS INTO THYMUS DNA 



Precursor 



32 

 I. P. J 4 



Orotic - C 

 Adenine - C^'* 

 Formate - C 



With P^^ they found that following irradiation less radio-a^^ivity was 

 incorporated into the phosphorus of the desoxynucleic molecule. P was in- 

 hibited 53 percent in the irradiated rats as compared with the normal controls. 

 This type of experiment had been done previously by Hardin Jones and others. 



Orotic acid, as a pyrimidine precursor, was inhibited to the extent of 

 66 percent into cytosine and 75 percent into thymine. Incorporation of adenine 

 labeled in the 8 position was not inhibited. As a matter of fact, the specific 

 activity in the irradiated sample was higher. So that Harrmgton and LavikV ) 

 expressed the adenine data as minus 25 percent inhibition into desoxynucleic 

 acid adenine, and minus 10 percent inhibition into desoxynucleic acid guanine. 



Formate is the precursor of the 2 and 8 position of purine and goes to 

 the methyl group of thymine. Formate assimilation into desoxynucleic acid 

 guanine was inhibited 48 percent; into desoxynucleic acid adenine it was inhibit- 

 ed 14 percent; and into thymine it was not depressed. Actually the specific 



