BIOSYNTHESIS OF NUCLEIC ACIDS 361 



precursors, no generalizations seem to be justified from these data because 

 of the varied experimental conditions and the technical difficulties involved 

 in determining some of the smaller observed incorporations. 



By comparing the specific activity of the phosphorus of the DNA with an average 

 vaiue throughout the experiment for the inorganic phosphorus of the organ, Hevesy 

 and Ottesen^' attempted to calculate minimum values for the daily renewal of the 

 DNA-P for each organ. By such a calculation, it was concluded that about half of the 

 newly formed DNA-P must represent "renewal" of the old molecules in a Jensen 

 sarcoma.'" '^"^ More recently, a similar calculation of the daily renewal of DNA-P 

 in rat liver and in intestine was based upon the total acid-soluble phosphorus of the 

 organs, and was compared with mitotic counts as determined after colchicine arrest 

 in metaphase.'°2 The results led to the conclusion that the incorporation of the P'^ 

 represented twice as much synthesis of DNA as was required for new cell formation, 

 and to the suggestion that each daughter cell receives a complete complement of new 

 DNA. However such calculations may be subject to considerable error because of the 

 difficulties in determining an average activity of the intercellular inorganic P over any 

 appreciable period of time,'"^"'"^ and the fact that it is now known that the inorganic 

 P is not in facile equilibrium with the immediate nucleic acid precursors.'"^'"* 



In all of the data recorded in Tables II and III, there is a distinct parallel 

 between the extent of cell division which is taking place in a tissue and the 

 incorporation of any of these precursors into the DNA of that tissue.^" '^^ 

 This is particularly evident with intestine and spleen where the large in- 

 corporations parallel the extensive new cell formation, and in the low in- 

 corporations into muscle, cartilage, and brain where essentially no mitosis 

 is taking place. In a man treated for a year with massive doses of P^^, no 

 P^2 was reported in the DNA of those tissues not undergoing mitosis (Table 

 II, column 6). Thus, although there is evidence that some additional DNA 

 synthesis or renewal may occur, the bulk of new DNA production does 

 appear to take place in conjunction with new cell formation. 



h. Incorporations into PNA 's of Individual Organs 



With all precursors the incorporations into PNA fractions exceed those 

 into the DNA's. The relative incorporations of formate into the purine 

 ribonucleotides or the PNA purines of several organs bear no apparent re- 

 lationship to its incorporation into the DNA's of those same organs (Table 



'"2 C. E. Stevens, R. Daoust, and C. P. Leblond, /. Biol. Chem. 202, 177 (1953). 



'"3 L. Ahlstrom, H. von Euler, G. Hevesy, and K. Zerahn, Arkiv Kemi, Mineral. 



Geol. A23, No. 10 (1946). 

 1"* C. Heidelberger, Advances in Cancer Research 1, 273 (1953). 

 1" C. P. Barnum and R. A. Huseby, Arch. Biochem. 29, 7 (1950). 

 ">6 D. B. Zilversmit, E. Enteman, and M. C. Fishier, /. Gen. Physiol. 26, 325 (1953). 

 '»■ J. Sacks, Cold Spring Harbor Symp. Quant. Biol. 13, 180 (1948). 

 '"* R. M. S. Smellie, W. M. Mclndoe, R. Logan, J. N. Davidson, and I. M. Dawson, 



Biochem. J. 54, 280 (1953). 



