350 GEORGE BOSWORTH BROWN AND PAUL M. ROLL 



b. Pyrimidine Derivatives 



Although free nucleic acid pyrimidines are not well utilized for nucleic 

 acid synthesis, it has been found that injection into rats of an alkaline 

 hydrolysate of N^^-labeled nucleic acid^^ resulted in extensive labeling of 

 polynucleotide pyrimidines, which indicated that combined pyrimidines can 

 be utilized for nucleic acid biosynthesis.^" Studies of the metabolism in the 

 rat of cytidine and uridine^^ labeled with N^^ (Hammarsten et al.^^) and of 

 cytidylic and uridylic acids-^ also labeled with N^^ have been made. It is 

 fortunate that almost identical experimental conditions in the two labora- 

 tories allow a reasonable comparison of the results (Table I). The pyrimi- 

 dines of both PNA and DNA are derived extensively from both cytidine 

 and cytidylic acid and the nucleoside and nucleotide are equally effective 

 as precursors. The incorporations, too, are of the magnitude of those ob- 

 served with adenine. In both types of nucleic acid there is a preferential 

 incorporation of both precursors into cytosine but with considerable trans- 

 formation into the other pyrimidine. Uridine and uridylic acid are less 

 effective precursors than the corresponding cytosine derivatives, but again 

 it is seen that these compounds are incorporated into the pyrimidines of 

 both PNA and DNA. Uridylic acid is a better precursor of PNA pyrimidines 

 than is uridine but the two compounds are equally well incorporated into 

 DNA pyrimidines. 



It has been pointed out®'* that since these free pyrimidines cannot be 

 utilized these results indicate that a transformation of ribose to deoxyribose 

 occurs without rupture of the ribosidic linkage. This hypothesis is validated 

 by studies^^ on the incorporation into rat nucleic acid of cytidine randomly 

 labeled with C^^ in both*^ the pyrimidine and the sugar. When cytidine, 

 uridine, deoxycytidine, and thymidine were isolated from the rat poly- 

 nucleotides, it was found that in each nucleoside the base and the sugar were 

 approximately equally labeled, indicating that the injected cytidine had 

 been incorporated as a unit and that the conversion of ribose to deoxyribose 

 had occurred with the ribosidic linkage intact. 



c. Specific Precursors of the DNA Bases 



Several N^^-labeled deoxyribonucleosides^^ have been investigated as pos- 

 sible nucleic acid precursors in the rat.^^ Hypoxanthine deoxyriboside 

 proved to ineffective. Deoxycytidine was found to be a precursor of cyto- 

 sine and thymine of DNA but was not at all utilized for PNA synthesis. 

 Thymidine was utilized for the synthesis of polynucleotide thymine only. 



^' Prepared from yeast grown with N'^Hs .^* 



" E. Hammarsten, P. Reichard, and E. Saluste, J. Biol. Chew. 183, 105 (1950). 



« I. A. Rose and B. S. Schweigert, J. Biol. Chem. 202, 635 (1953). 



^^ Prepared from Euglena gracilis grown in the presence of C^^Oi .^^ 



