BIOSYNTHESIS OF NUCLEIC ACIDS 367 



finally reaches the polynucleotides may not be that which is introduced in the original 

 synthesis de novo of a purine derivative (Chapter 23) but may be one which, like ade- 

 nine or orotic acid, is introduced at some later stage in the assembly line. 



The existence^^'^' of facile incorporation of administered adenine for the synthesis 

 of liver PNA's (Table IV) may furnish a partial explanation of the enhanced liver 

 PNA : DNA ratios obtained with it, and a similar factor may play a role with orotic 

 acid.^" The observations that the purine ribosides or ribotides are not incorporated 

 into DNA of the total viscera to a great extent, although corresponding pyrimidine 

 ribosyl derivatives do lead to a considerable renewal of the DNA polynucleotide 

 pyrimidines, cannot yet be interpreted since the incorporations of those ribosyl 

 derivatives into individual organs have not yet been studied. 



The proportionately greater incorporation of all precursors into the DNA 

 of regenerating liver does augment the evidence in Table II that a more 

 extensive DNA synthesis is associated with mitosis. Furst et aZ.'^'"^ em- 

 phasized that the incorporation of adenine was extremely small in the ab- 

 sence of extensive mitosis, and, in particular, that the long-term retention 

 of the isotope once incorporated demonstrated a pronounced biochemical 

 stability of the bulk of the DNA, and that such a property may be perti- 

 nent to the candidacy of DNA for a role as a part of the genetic material. 

 The proteins of the nucleus have been demonstrated by Hammarsten and 

 co-workers"" '^^^-'^^ to be extensively renewed by glycine nitrogen, and 

 Daly et al}"^^ have carried this one step further and showed that the residual 

 protein is renewed more extensively than is the histone, but no protein has 

 yet displayed a nondynamic character comparable to that of the bulk of 

 the DNA. 



The deductions regarding the quantity of DNA renewed in a growing 

 tumor, "'•^*'' or in normal liver and intestine,'"^ show that the synthesis of 

 DNA is in excess of that required for new cell production and suggest some 

 renewal of DNA. The relative incorporations observed for glycine, formate, 

 and serine in nondividing tissues have frequently been considered^^'^^'^^'"^ 

 us, 129-131 ^Q \yQ incompatible with the evidence suggesting a comparatively 

 limited turnover of DNA. Initially, these differences in the relative incor- 

 porations of glycine or formate and adenine, and even the smaller differences 

 between adenine and phosphate, could be taken^^^ as suggestive that indi- 

 vidual moieties of the polynucleotides, or at least of their immediate pre- 

 cursors, might be renewed independently. Specific investigations, involving 

 degradations to locate the positions of the isotope, of the possible indepen- 



'" E. Hammarsten, in "Isotopes in Biochemistry" (Wolstenholme, ed.), p. 203. 



Blakiston, Philadelphia, 1951. 

 128 M. M. Daly, V. G. Allfrey, and A. E. Mirsky, J. Gen. Physiol. 36, 173 (1952). 

 >" D. Elwyn and D. B. Sprinson, J. Am. Chem. Soc. 72, 3317 (1950). 

 130 E. P. Tyner, C. Heidelberger, and G. A. LePage, Cancer Research 12, 158 (1952). 

 '" J. Brachet, Actualites biochim. No. 16 (1952). 

 132 G. B. Brown, Cold Spring Harbor Symposia Quant. Biol. 13, 43 (1948). 



