398 K. M. S. SMELLIE 



the uptake of isotope by the DNA of hver and spleen of tumor-bearing 

 animals was greater than in the controls, and noted that the increment in 

 uptake of P*^ by the DNA of mouse liver showed an increase with increas- 

 ing age of the tumor. A further observation bearing on this effect is the find- 

 ing of Kelly and Jones^" that the administration of homologous tissue 

 extracts to mice for some days, leads to an increased incorporation of P^^ 

 into the DNA of certain organs. The metabolism of the nucleic acids of 

 neoplastic tissues has recently been reviewed by Heidelberger.^^ 



2. PNA 



a. Precautions Necessary in the Study of PNA Metabolism with P^^ 



Two factors complicate attempts to study the metabolism of PNA by 

 means of isotopic phosphorus. The first is that the PNA within the cell 

 cannot be regarded as homogeneous in origin since it is found in the various 

 morphological components of the cell. Moreover, as we shall see later, the 

 PNA of the cell nucleus is metabolically very different from that of the 

 cytoplasm. The second factor relates to the danger of contamination of the 

 PNA with other substances which are more highly radioactive than the 

 PNA itself, and which must now be considered. 



In most instances, determination of radioactivity has been made on 

 samples of PNA isolated in a purified form by one or other of the methods 

 described in the literature.'--^"" While these methods are satisfactory for 

 most purposes, they suffer from the major disadvantage that recovery 

 may not be quantitative and that a trace of some radioactive contaminant 

 may be present in the final product. In an attempt to overcome the difficul- 

 ties concerning the combination of quantitative measurement of the 

 nucleic acids in tissues simultaneously with isotope measurements, David- 

 son et al?^-'' have suggested determining the uptake of P^^ into the PNA 

 and DNA of a tissue by measurements on the corresponding fractions ob- 

 tained by the application of a fractionation scheme such as that of Schmidt 

 and Thannhauser,-^ which has been described in Chapter 16. Several work- 

 ers have attempted to measure the radioactivity of tissue PNA and DNA by 



20 L. S. Kelly and H. B. Jones, Am. J. Physiol. 172, 575 (1953). 



2' C. Heidelberger, Advances in Cancer Research 1, 273 (1953). 



=2 J. N. Davidson, S. C. Frazer, and W. C. Hutchison, Biochem. J. 49, 311 (1951). 



23 E. Hammarsten, Acta Med. Scand. Suppl. 196, 634 (1947). 



24 J. N. Davidson and R. M. S. Smellie, Biochem. J. 52, 599 (1952). 



25 E. Volkin and C. E. Carter, J. Am. Chem. Sac. 73, 1516 (1951). 



26 J. N. Davidson, M. Gardner, W. C. Hutchison, W. M. Mclndoe, W. H. Raymond, 

 and J. F. Shaw, Biochem. J. 44, xx (1949). 



27 J. N. Davidson, M. Gardner, W. C. Hutchison, W. M. Mclndoe, and J. F. Shaw, 

 Abstr. 1st Intern. Congr. Biochem., Cambridge, Engl. p. 252 (1949). 



28 G. Schmidt and S. J. Thannhauser, J. Biol. Chem. 161, 83 (1945). 



