BIOLOGICAL ROI-E OF DEOXYPENTOSE NUCLEIC ACIDS 457 



subject will be considered briefly, from the vantage point that has been 

 attained by looking upon DNA's as genetic determinants. 



1. Metabolic Stability of DNA 



The facts already presented in Chapters 25 and 26 have indicated that 

 atom groups from intermediary metabolites are not introduced as readily 

 into tissue DXA's as they are into PXA's, proteins, and soluble cell con- 

 stituents. This is true for the utilization of isotopically labeled nitrogen, 

 carbon, and phosphorus compounds, and of intact purine and pyrimidine 

 bases. It has been satisfactorily established by Hevesy, and others since, 

 that an isotope is incorporated into DXA mainly when there is mitotic 

 division, as in growing tissue, regenerating liver, or tumors. When once 

 incorporated, the tagged atoms disappear from cellular DXA far slower 

 than from PXA and other sites. 



This metabolic stability is very likely an important requirement for 

 materials which are to serve as pattern-makers for inheritance. Every 

 growing organism has to build up DXA, but, when not actively growing, it 

 is more likely to keep its biological heritage intact if it can minimize the 

 participation of that DXA in the wasteful equilibria which involve the 

 breaking down and rebuilding of so many cellular constituents. 



As pattern-making components, DXA-containing structures have to be 

 duplicated before the cell can divide. It is interesting in this connection 

 that the newly incorporated DXA-phosphorus in growing liver and intes- 

 tinal mucosa^^^ (and also lung in a later work^^^) has been reported to be 

 just about sufficient to supply new DXA-P to both daughter cells from 

 each mitosis. In this work, the amount of isotopic phosphorus incorporated 

 into the tissue DX'^A after an injection of labeled phosphate was related to 

 the mitotic activity of the tissue. It is implied that the preexisting DXA- 

 phosphorus, and probably the DXA itself, is not retained but is entirely 

 renewed during a mitosis. This most interesting inference should not 

 be accepted literally at present, since the calculation is fraught with 

 many hazards and may be unreliable. It depends upon the accuracy of 

 assay of the number of mitoses, upon the assumption that the analytical 

 changes in DXA-P are directly and exclusively referable only to these 

 dividing cells, and upon the assumption of the nature and isotope level of 

 a changing precursor pool; and it is very critically dependent upon the- 

 purity of the assayed DX^'A fraction. Even if correct, the results may merely 

 indicate that other cells, besides the ones seen in mitosis, are duplicating 

 their DX'^A. It was not feasible in the present instance to demonstrate the 

 destruction or elimination of preexisting DXA ; in most studies of this sub- 



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

 '" C. E. Stevens, R. Daoust, and C. P. Leblond, Can. J. Med. Sci. 31, 263 (1953). 



