126 S. S. COHEN 



report of Brody (1957), indicating that in developing placenta the ribo- 

 nuclease activity is roughly proportional to the rate of growth of the tissue. 

 This has been taken to suggest a possibly direct relation between RNAase 

 activity and the cellular synthesis of RNA. Ledoux et al. (1957) have also 

 shown a linear relation between the RNAase and RNA contents of the normal 

 organs of mice and rats. 



The problem of demonstrating nucleic acid turnover in rat liver has 

 recently been re-examined in great detail (Swick et al., 1956; Swick and Koch, 

 1957). These workers have analyzed the difficulties stemming from the use of 

 a single dose of isotope as a consequence of varying pool sizes, exchange, 

 transfer, and reincorporation phenomena, variability of turnover rates of 

 fractions of the substance under investigation and of its precursors. They 

 have used isotope (C^^Oa and P^^) continuously under conditions which 

 eliminate transient changes in the specific activity of mtermediate pools and, 

 having developed corrections for various reutihzation phenomena, have 

 obtamed equations which permit the estimation of incorporation and dis- 

 appearance of isotope from the nucleic acids of the growing rat. Their results 

 affirm the high degree of stabihty of DNA and the nonreplaceabihty of its 

 atoms and indicate that the average fife of all liver cells is about 150 days. 

 On the other hand, the half-hfe of substantially aU of the RNA of the same 

 tissue was on the order of 4 to 6 days. 



Recent results •with, mmatural purine and pyrimidine bases have provided 

 another type of evidence pointing to exchange or RNA turnover in bacteria, 

 and, in one instance, to the possibility of this phenomenon with DNA. In 

 studies with 8-azaguanine in B. cereus by Matthews and Smith (1956), 

 bacteria were prepared in which the RNA contained the unnatural base. The 

 growth of such bacteria is inhibited, but may be renewed in the presence of 

 guanine. On supplying the normal purine, a normal growth rate is restored 

 and 8-azaguanine disappears from the RNA much more raj^idly than can be 

 accounted for by the dilution of existing RNA by newly synthesized RNA 

 containing guanine. These results then suggest an exchange of guanine for 

 azaguanine without breakdowTi of RNA or a rapid degradation and resyn- 

 thesis of polynucleotides. In a more extensive study of this phenomenon, 

 Mandel (1957) has excluded the possibility of a simple replacement of 

 azaguanine by guanine. 



Zamenhof and his collaborators have described a reversible replacement 

 of th}Tnine in DNA by 5-bromouracil in a thymine-rcquiring strain of E. coll 

 (Zamenhof et al., 1956b). It has been shown further that the replacement is 

 accompanied by an incorporation of P^^ with the new base, indicating that 

 the new base is incorporated as a new nucleotide (Price, T. D. et al., 1956). The 

 experiments reported to date state that when organisms which are no longer 

 growing are incubated for considerable periods, e.g., 20 hours, in the presence 



