150 Alma Howard and S. R. Pelc 



into the DNA of non-growing liver, but that there is extensive incor- 

 poration into the DNA of regenerating liver, and in long-term survival 

 experiments there is extensive retention of that adenine once incor- 

 porated. That has been rather hard to correlate with the original 

 observations of Hammarsten with [^^N] glycine and the subsequent 

 observations of LePage and Heidelberger with [^*C] glycine, which 

 enters the DNA of non-gTowing tissues. Currently we have carried out 

 an experiment in which [^^N] glycine and [^^C] adenine have been fed 

 simultaneously, both to normal rats and to rats that had been partially 

 hepatectomized. The combined results confirm all the previous 

 experiments, that is, a certain amount of glycine will go into the DNA 

 when adenine does not; and that the relative incorporation of the two 

 compounds into the two types of nucleic acids in rest and into the two 

 nucleic acids in regeneration are not parallel to one another. 



I think the simplest thing is to say that there are two mechanisms 

 for formation of DNA. I would hesitate to call it two DNA's, but it 

 might be "core" versus side-chains. Certainly there is an incorporation 

 of glycine, formate, and other purine precursors which is not parallel 

 to the incorporation of preformed purine given to the animal. We have 

 also extended the adenine retention data to a 96-day experiment, at 

 which time the DNA adenine, incorporated during regeneration, still 

 contained 1100 counts, and by that time the isotopically labelled PNA 

 adenine had been lost by dynamic equilibrium down to 7 counts, thus 

 confirming a long term stability for at least some DNA. 



Leblond: Does your work suggest an explanation for what has been 

 observed with phosphorus? 



Brown: I would say that the phosphorus and the adenine are fairly 

 well correlated, as can be the results with glycine and formate. We have 

 also given formate to normal animals, with non-growing liver, and the 

 formate which is incorporated into the 2 and 8 positions of the DNA 

 purines also disappears as though it were in dynamic equilibrium. At 

 present the simplest thing is to say that there is some dynamic DNA, 

 some static DNA. The adenine and the phosphorus measure chiefly 

 the static DNA, which Dr. Howard has indicated is only formed prior 

 to mitosis. I hesitate to refer to two molecules; it can be two portions 

 of the same molecule. 



Holmes: If you use phosphorus in brain tissue, w^here there is prac- 

 tically no mitosis, you get very little incorporation in the DNA. You 

 would agree with that? 



Brown: We haven't done anything on brain tissue, but since there is 

 very little cell division, that would fit the picture that phosphorus and 

 the preformed purine are giving one type of result and the purine pre- 

 cursors are giving another type. 



Heidelberger: I have a couple of slides that I hope to show to- 

 morrow on this glycine incorporation that Dr. Brown just mentioned. 

 We get very extensive incorporation of glycine into the purines of the 

 deoxyribonucleic acid of resting liver. 



Howard: I think that the question of the discrepancy between the 

 amount of DNA and the mitotic rate is due in part to the fact that, 



