374 



GEORGE BOSWORTH BROWN AND PAUL M. ROLL 



I " 



NON-GROWING 



PNA ONA 



,m 



REGENERATING 



PNA DNA 



Fig. 3. Per cent of liver PNA and 

 DNA purines derived from each pre- 

 cursor after simultaneous administration 

 of adenine and glycine. (Note that the 

 scale is 20 times larger in the lower sec- 

 tion.) Furst, et al.'^^ 



PNA Guonine 



20 40 60 80 



Time in hours 



Fig. 4. Isotope contents at different 

 stages of regeneration in rat liver. Gly- 

 cine-N^^ injected at various times after 

 operation and animals sacrificed eight 

 hours later. Hammarsten.'^' 



shows several distinct differences between the renewals of individual bases in each of 

 two fractions, but cannot account for a continuous synthesis of some small portion 

 of the DNA while the bulk remains static. 



In the one instance where the simultaneous incorporations of two precursors into 

 the same moieties were studied in both normal and in regenerating liver, "^ the relative 

 differences between the incorporations of glycine and adenine into the PNA and DNA 

 purines of the nongrowing and rapidly growing livers were different, and suggests 

 that if two mechanisms are involved they do not function to the same relative extents 

 in the nongrowing and the rapidly growing tissues. These results (Fig. 3) indicated 

 that in the DNA of the rapidly growing livers the incorporation of glycine nitrogen 

 was 6- to 9-fold greater than into the DNA of the nongrowing, while with adenine 

 there was a 25- to 32-fold difference between the growing and nongrowing livers. In 

 the case of the PNA there was a much greater incorporation of the glycine in the 

 regenerating liver but there was only a small difference in the extent of incorporation 

 of adenine into the PNA under the two conditions. Anderson and Aqvist'^^ find that 

 incorporations of orotic acid-N'^ and phosphate-P'^ into the pyrimidines and the 

 phosphate also bear different relations to one another in normal and in regenerating 

 liver (Table V, lines 113-116). 



A series of studies of the parallelism of the incorporations into protein and into 

 polynucleotides of glycine administered at various time intervals after the start of 

 regeneration of rat liver introduced the additional complication of the stage of re- 

 generation of the livers. An impressively complex curve (Fig. 4) with multiple maxima 

 for the incorporations into the purines was recorded.'" No explanation for the nature 

 of the curves was offered and none yet seems apparent, but these curves are an out- 

 standing example of the complexity which can be encountered in isotope incorpora- 

 tion studies. 



Final decisions regarding the apparent existence of two mechanisms of 

 synthesis, and of their characteristics, must await further information re- 



