BIOSYNTHESIS OF NUCLEIC ACIDS 347 



able to detect a very slight conversion of guanine to PNA adenine. In the 

 black mouse, a small but significant utilization of guanine-2-am?'rio-l ,3-N3^* 

 was detected.'® 



Hammarsten and Reichard'^ investigated the incorporation of guanosine 

 uniformly labeled with N^^ '* and concluded that it was not utilized for 

 nucleic acid synthesis by the rat. However, by the use of guanosine-8-C",^^ 

 a slight but definite incorporation (0.3 %) was found^^ into the guanine of 

 the rat visceral PNA, with no significant conversion of guanosine to PNA 

 adenine. Yet the experiment^" in which mixed N'^ nucleotides were injected 

 into rats had indicated that this mixture had contained a quite effective 

 guanine precursor. An explanation of that latter result became apparent 

 when it was found^* that guanylic acid-N^* was well incorporated into the 

 guanine of the PNA of rat viscera and may have also been used to a slight 

 extent for the formation of DNA guanine. 



It was found that in L. casei'^^ the incorporation of guanine and its deriva- 

 tives is as extensive as that of adenine and its derivatives. Guanine is well 

 incorporated into PNA, guanosine'^ is a poorer precursor, and guanosine- 

 3'-phosphate is well utilized whereas guanosine-2'-phosphate is not.'* 



c. Other Purines and Derivatives 



In an effort to determine the nature of the intermediates involved in the 

 conversion of adenine to guanine, several nonnucleic acid purines have 

 been investigated as possible nucleic acid precursors. Isoguanine,^^ hypoxan- 

 thine, xanthine,"*^ and uric acid"" (labeled with N'^) were each fed to rats 

 and were found to be ineffective as nucleic acid precursors. It should be 

 noted that the studies with hypoxanthine, xanthine, and isoguanine in the 

 rat involved N' ^-labeled samples and that trace incorporations such as that 

 subsequently detected for guanine are not excluded. However, 2,6-diamino- 

 purine^*'^^ is incorporated into polynucleotide guanine in the rat; in one 

 experiment as much as 4 % of the guanine was found to have been derived 

 from the 2 , 6-diaminopurine but no conversion into polynucleotide adenine 



36 G. B. Brown, A. Bendich, P. M. Roll, and K. Sugiura, Proc. Soc. Exptl. Biol. Med. 



72, 501 (1949). 

 3' E. Hammarsten and P. Reichard, Acta Chem. Scand. 4, 711 (1950). 

 '* Prepared from Escherichia coli grown with N'^jij .'^.'^ 

 39 P. Reichard and B. Estborn, J. Biol. Chem. 188, 839 (1951). 

 ^o M. E. Balis, D. H. Levin, G. B. Brown, G. B. Elion, H. VanderWerif, and G. H. 



Hitchings, J. Biol. Chem. 196, 729 (1952). 

 " A. Bendich, G. B. Brown, F. S. Philips, and J. B. Thiersch, J. Biol. Chem. 183, 



267 (1950). 

 « H. Getler, P. M. Roll, J. F. Tinker, and G. B. Brown, /. Biol. Chem. 178, 259 (1949) . 

 « G. B. Brown, P. M. Roll, and L. F. Cavalieri, /. Biol. Chem. 171, 835 (1947). 

 « A. Bendich and G. B. Brown, J. Biol. Chem. 176, 1471 (1948). 

 « A. Bendich, S. S. Furst, and G. B. Brown, J. Biol. Chem,. 185, 423 (1950). 



