METABOLISM OF THE NUCLEIC ACIDS 395 



typified by liver, kidnej^ and brain, in which the isotope content is small 

 and cell division minimal in the normal adult animal. It has been found' '^ 

 that there is a decrease with age in the rate of formation of labeled DXA 

 in thymus, lymph nodes, and spleen and that the uptake of P^' by the 

 DNA of weanling rat liver is more rapid than in the adult animal.^ This 

 work lends support to the conception that P^^ incorporation into the DNA 

 of a tissue provides an indication of the rate of cell division in that tissue. 

 Further evidence for this view comes from the work of Hevesy and Ot- 

 tesen,* who were unable to obtain incorporation of radioactive phosphorus 

 into the DNA of nucleated hen erythrocytes (nondividing cells) incubated 

 in the presence of labeled phosphate, and also from the work of Howard 

 and Pelc,^'® who have shown by their autoradiograph technique on bean 

 roots that a cell which has completed its last division and is differentiating 

 does not synthesize DNA. 



Stevens et at.'' have compared the rate of incorporation of P^^ into the 

 DNA of rat liver and intestine with the rate at which new cells are formed 

 by mitosis in these tissues. They found that twice as much phosphorus ap- 

 peared in the DNA as could be accounted for by the synthesis of additional 

 DNA, and suggest that all the DNA derived from the mitosis is newly 

 formed. 



h. The Effect of Physiological and Pathological Changes on the Uptake of 

 Radioactive Phosphorus by DN^A 



The conclusions of the previous section indicate that changes in the 

 physiological or pathological state of a tissue which tend towards increased 

 cell division will lead to increased incorporation of radioactive phosphorus 

 into the DNA of the tissue. The results summarized in Table II make it 

 clear that such indeed is the case. Thus regenerating rat liver, fetal rabbit 

 liver, rat hepatoma, and pregnancy-stimulated mammary gland, as well 

 as carcinomatous mammary gland, all show greatly increased incorporation 

 of isotope as compared with the corresponding normal tissue in each case.'^-ie 



1 E. Andreasen and J. Ottesen, Acta Physiol. Scand. 10, 258 (1945). 



2 G. Hevesy, Advances in Enzymol. 7, 111 (1947). 



3 R. M. S. Smellie, W M. Mclndoe, R. Logan, J. X. Davidson, and I. M. Dawson, 

 Biochem. J. 54, 280 (1953). 



* G. Hevesy and J. Ottesen, Nature 156, 534 (1945). 



^ A. Howard and S. R. Pelc, Ciba Conf. on Isotopes in Biochem., London p. 138 (1951) . 



6 S. R. Pelc and A. Howard, Exptl. Cell Research Suppl. 2, 269 (1952). 



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



8 G. Hevesy and J. Ottesen, Acta Physiol. Scand. 5, 237 (1943). 



' E. Hammarsten and G. Hevesy, Acta Physiol. Scand. 11, 335 (1946). 

 '» A. H. Payne, L. S. Kelly, and H. B. Jones, Cancer Research 12. 666 (1952). 

 " R. M. S. Smellie, E. R. M. Kay and J. N. Davidson, unpublished results. 

 12 A. M. Brues, M. M. Tracy, and W. E. Cohn, J. Biol. Chem. 155, 619 (1944). 



