356 GEORGE BOSWORTH BROWN AND PAUL M. ROLL 



the "killer" type (51-7K) and the kappa-free "sensitive" type (51-7SB), showed" a 

 considerable difference in the extent to which adenine was converted into PNA 

 guanine. Guanine was not tested in the paramecia, and in Fig. 2 the bars represent 

 the relative transformation of 2,6-diaminopurine into adenine. 



Only adenine has been tested in man in vivo.^ It is utilized for the syn- 

 thesis of both polynucleotide adenine and guanine of the leucocytes (in a 

 chronic lymphatic leukemia). When human leukemic leucocytes were incu- 

 cated in serum, adenine and guanine were utilized but were not intercon- 

 verted, and diaminopurine was transformed into polynucleotide guanine 

 only. 



The meager evidence available on the utilization of nucleosides indicates that 

 there are also species differences in the modes of metabolism of the ribosyl deriva- 

 tives. The utilization of ribose derivatives with maintenance of the integrity of the 

 ribosyl linkage is suggested by the specific growth response of some of the more 

 fastidious organisms to pyrimidine or purine ribosides or ribotides,**' and by the 

 incorporation of pyrimidine ribosyl derivatives^"-^*''"** by the rat. In L. casei 

 several ribosides exhibit less facile interconversions than do the corresponding free 

 purines (cf. Fig. 6), which suggests'^ that they are utilized as such and not via the 

 free purines. The appearance of considerable amounts of the ribose of guanylic acid 

 in the other nucleosides from the nucleic acids of L. leichmanii^^ indicates the occur- 

 rence of extensive transglycosidation (Chapter 24). In E. coli B the cytosine of cyti- 

 dine is incorporated independently of its ribosyl moiety, with but small amounts of 

 isotope appearing in any of the polynucleotide ribose. 



III. Comparative Incorporations into Various 

 Nucleic Acid Fractions 



The ability to detect the metabolic replacement or renewal, of cell con- 

 stituents is a unique virtue of isotopic tracers, but a word of caution is 

 desirable regarding the dangers of overinterpretation of data thus accumu- 

 lated. The incorporations observed are not only the result of both forma- 

 tion of new labeled molecules and the concurrent loss of some of these dur- 

 ing the period of the experiment, but are also affected by the various 

 equilibria in which the series of intermediates, through which the precursors 

 must pass en route to the final products, are involved. Precursors of different 

 degrees of complexity may enter a single assembly line at widely separated 

 points, and the time courses of the incorporations of two precursors may be 

 quite different by virtue of the fact that the one may pass into a slowly 

 renewed intermediate, while the other may by-pass that intermediate and 

 be incorporated only into rapidly renewed intermediates. The relative 

 extents to which precursors, particularly when introduced in excess of 

 physiological concentrations, are shunted into catabolic, or alternate ana- 

 bolic, pathways can also influence the dilution factors. It is to be hoped 



«8 L. D. Hamilton, Nature 172, 457 (1953). 



«' W. S. McNutt, Fortschr. Chem. org. Naiurstoffe 9, 401 (1952). 



