406 R- M. S. SMELLIE 



that in rats and mice adenine is used as a precursor of nucleic acid adenine 

 and, to a lesser extent, of guanine. Guanine, however, is poorly utilized by 

 rats as a nucleic acid purine precursor and virtually no conversion of 

 guanine to adenine takes place. In yeasts, there is considerable conversion 

 of adenine to nucleic acid guanine, the reverse reaction not occurring to a 

 significant extent.'^' 



The metabolism of the nucleic acids in rats has been studied by Furst 

 et al?^ using adenine labeled in positions 1 and 3 with N^*. They observed 

 that in whole viscera and in resting liver the PNA purines contained ap- 

 preciable amounts of isotope, while incorporation into the DNA purines 

 amounted to only about 1 % of that in the PNA purines. Examination of 

 the incorporation of labeled adenine into the PNA and DNA purines of 

 regenerating liver showed considerable uptake of isotope by both. It was 

 noticed that while only about 11 % of the W^ present in the PNA at 5 

 days was retained at 21 days after administration of the labeled adenine, 

 the corresponding value for DNA was 75%. This indicates a very low 

 rate of renewal of DNA nitrogen after the period of hyperplasia. The ratios 

 of isotope content of PNA/DNA in different tissues after administration 

 of labeled adenine are shown in Table V of Chapter 25, and it is clear from 

 these results that the extent of utilization of labeled adenine by DNA of 

 resting liver is much lower than by PNA. In regenerating liver, on the other 

 hand, or in proliferating tissues such as intestine, the PNA and DNA ap- 

 pear to utilize preformed adenine to about the same extent. 



The uptake of adenine by the PNA and DNA of resting liver contrasts 

 sharply with the results which have already been discussed with P^^-, 

 C^'-, C"-, and N^*-labeled small-molecule precursors. This discrepancy has 

 been further investigated by Furst and Brown,'^" who have shown ^by the 

 simultaneous administration of glycine-N'^ and adenine-C'^ that the pat- 

 tern of uptake of the former by liver PNA and DNA is quite different from 

 that obtaining with adenine. Thus while glycine is extensively utilized by 

 both PNA and DNA, only the PNA of resting liver can be shown to con- 

 tain appreciable amounts of administered adenine. That adenine can be 

 utilized in the synthesis of DNA purines is clearly shown from experiments 

 on regenerating liver,'^" '^^ on intestine,^* and on hepatoma.*^ Furst and 

 Brown have therefore suggested that two types of DNA, differing in met- 

 abolic activity, may be present in a single tissue. One of these DNA's may 

 be renewed continually from small-molecule precursors while the other, 

 which may play a proportionately greater part during rapid tissue growth, 

 could draw upon preformed purines as precursors (see Chapter 25). Some 

 support for the conception that two different mechanisms are available 

 for DNA synthesis comes from the recent report^^ that, while whole body 



" A. C. Griffin, W. E. Davis, Jr., and M. O. Tifft, Cancer Research 12, 707 (1952). 

 82 H. Harrington and P. S. Lavik, Federation Proc. 12, 214 (1953). 



