BIOSYNTHESIS OF NUCLEIC ACIDS 377 



nucleic acid synthesis. It was later demonstrated"' that A-methopterin 

 inhibition could be partially relieved by treatment of the animals with folic 

 acid. It is interesting that, in mice bearing a strain of leukemia refractory 

 to treatment by A-methopterin, the incorporation of formate into the leu- 

 kemic cells was increased by A-methopterin although the usual inhibition 

 of incorporation into visceral nucleic acids was observed."' 



Goldthwait and Bendich^^ investigated the simultaneous incorporation 

 of formate-C'^ and adenine-N^^ into the nucleic acids of aminopterin-treated 

 and control rats, and found that the incorporation of formate was depressed 

 by the inhibitor to a much greater extent than was the incorporation of 

 adenine. This effectively demonstrated that the inhibition of nucleic acid 

 synthesis by means of aminopterin is not a result of a specific interference 

 with nucleic acid synthesis per se, but rather that it can be attributed to 

 interference with the incorporation of formate into purines and into thy- 

 mine. 



Lowe and Barnum'^" found that the PNA content of the Uver of folic 

 acid-deficient megaloblastic monkeys is lower than that of normal animals 

 but that foUc acid therapy resulted in a PNA content higher than normal. 

 They also found that the deficient animals incorporated P^- into hver PNA 

 less effectively than did the normal animals and that this defect in incor- 

 poration was also amenable to treatment with folic acid. 



h. Vitamin Bu 



Experiments on the growth of microorganisms have indicated that in 

 nucleic acid biosynthesis vitamin B12 is concerned with the formation of 

 deoxynucleosides (particularly thymidine) ^^^""' although it probably also 

 has other functions as welP'*'*""^ (see Chapter 24). The incorporation of P'^ 

 into L. leichmanii is stimulated by Bi2.^'*^ The PNA and DNA contents 

 (but not the amounts per cell) of the livers of vitamin Bi2-deficient rats are 

 less than those of the livers of normal animals. ^''^ This deficiency also results 

 in a decreased incorporation of glycine-N'^ into the nucleic acids (and pro- 

 tein). ^*^ The administration of vitamin B12 to deficient rats was followed by 



•" H. E. Skipper, C. Nolan, M. A. Newton, and L. Simpson, Cancer Research 12, 369 

 (1952); H. E. Skipper, L. L. Bennett, Jr., and L. W. Law, ibid. 12, 677 (1952). 



■'o C. U. Lowe and C. P. Barnum, Arch. Biochem. and Biophys. 38, 3.35 (1952). 



" W. Shive, J. M. Ravel, and R. E. Eakin, /. Am. Chem. Soc. 70, 2614 (1948). 



« L. D. Wright, H. R. Skeggs, and J. W. Huff, J. Biol. Chem. 175, 475 (1948). 



" E. Kitay, W. S. McNutt, and E. E. Snell, J. Biol. Chem. 177, 993 (1950). 



" H. R. Skeggs, J. Cellular Comp. Physiol. 38, Suppl. 1, 227 (1951). 



45 F. Weygand, A. Wacker, and F. Wirth, Z. Naturforsch. 6b, 25 (1951). 



4« M. Downing, L A. Rose, and B. S. Schweigert, J. Bacterial. 64, 141 (1952). 



" I. Z. Roberts, R. B. Roberts, and P. H. Abelson, J. Bacteriol. 68, 709 (1949). 

 [. \. Rose and B. S. Schweigert, Proc. Soc. Exptl. Biol. Med. 79, 541 (1952). 



