366 GEORGE BOSWORTH BROWN AND PAUL M. ROLL 



that into the purines of the DNA by a much greater margin," with values 

 for the PNA:DNA ratio ranging from 35 to 73 (Table V, Hnes 91-101, 104, 

 108, and 110). The pyrimidine precursor, orotic acid, also results^" in 

 PNAiDNA ratios of the magnitude found with adenine (lines 102 and 

 113). 



Throughout the period of regeneration of the liver of partially hepatec- 

 tomized rats, a greatly increased incorporation of adenine into the DNA 

 fraction resulted in PNAiDNA ratios of only 1.4 to 2.6 (Table V, hnes 92 

 and 106) and demonstrated that it was not an inability to utilize adenine 

 for DNA synthesis which was responsible for the high ratios in normal liver. 

 When similarly treated rats were allowed to survive for a period of time, 

 the isotope which had been incorporated into the DNA purines during the 

 period of rapid growth of the liver was extensively retained, while that in 

 the PNA was largely lost, which resulted in PNA:DNA ratios of 0.3 after 

 21 daysi« and 0.01 at 96 days'^^ (hnes 93 and 96). Later^s^^^ the retention 

 of the isotope of formate-C^" which was incorporated into the various bases 

 of the DNA during the period of regeneration of liver was found to be ap- 

 preciably greater than was the retention of that incorporated into normal 

 liver (Table V, line 59, and Table VI). 



It should be noted that in the intestine all of the precursors, glycine 

 (Table V, hnes 72, 73, 83, 84, and 118), formate (Table V, line 120, and 

 Table II), adenine (Table V, lines 117 and 119), and phosphate (lines 17, 42, 

 and 43), result in PNA: DNA ratios of approximately 1.5 to 2, so that the 

 incorporations into this rapidly growing tissue are analogous to those in 

 regenerating liver. 



The marked contrasts between the incorporations of the various pre- 

 cursors into liver PNA and DNA are amply confirmed by the several ex- 

 periments cited in Table V, including several instances where simultaneous 

 administration of the two precursors labeled with different isotopes fur- 

 nished direct comparisons under identical experimental conditions (lines 

 103-120). This was done with glycine and adenine in two laboratories;'*'"'' 

 with formate and adenine;'^ with glycine and phosphate ;'^^ and with orotic 

 acid and phosphate. '^^ The incorporations of four precursors into gross nu- 

 cleic acid fractions were also compared under similar conditions'"" (lines 22, 

 23, 60, 61, 69, and 97). 



There is thus a generally good agreement that lower ratios are obtained 

 with glycine or formate and higher ratios with adenine, orotic acid, and P^^. 



In view of the findingsi^** that the relative incorporations of simultaneously ad- 

 ministered orotic acid and phosphate into liver nucleic acid fractions are not fully 

 parallel, it may be that they and adenine are incorporated at similar, but not identi- 

 cal, stages of the biosynthesis pathway. It was noted'^' that, when administered 

 simultaneously, relatively more phosphate than glycine carbon appeared in the 

 purine nucleotides of the PNA at the shorter time intervals. The phosphorus which 



