ROLE OF NUCLEIC ACIDS 73 



ribonuclease simply because the enzyme cannot enter intact liver mito- 

 chondria. 



The results reviewed above show that ribonuclease acting on living cells 

 brings about various types of damages. In favourable cases, it can selec- 

 tively inhibit the synthesis of protein or of certain proteins without acting 

 upon general metabolism and energy production, or without affecting the 

 synthesis of many various cell constituents. The mode of action of the 

 enzyme is not completely analysed, but inhibition of protein synthesis 

 coincides with the breakdown of certain RNA fractions especially soluble 

 RNA. 



It would seem that a limited degradation or modification of certain RNA 

 fractions is enough to stop protein synthesis, or to cause modifications in 

 the properties of the proteins produced. 



(b) Modification of RNA by analogues of purines and pyrimidines. Many 

 analogues of the natural purines and pyrimidines have been prepared by 

 chemical synthesis. Some of them proved to be potent inhibitors of growth 

 for certain animal or plant cells and for certain strains of bacteria (Elion 

 et al., 1954). It is likely that substances of this kind interfere with the meta- 

 bolism, the synthesis or the function of nucleic acids or nucleotidic com- 

 pounds. Present knowledge of the mode of action of these analogues is 

 actually rather poor, restricted as it is to the case of a few compounds and a 

 few organisms or biochemical systems. It is, however, sufiicient already to 

 show that purine and pyrimidine analogues can interfere in many ways 

 with the metabolism of the natural parent products, and more indirectly 

 with other metabolic processes as well. This is illustrated by the following 

 examples: 5-fluoro-uracil inhibits methylation in the synthesis of thymine 

 (Bosch et al, 1958; Cohen et al, 1958; Heidelberger ^^ a/., 1957; Eidinoff 

 et al., 1957; Harbers et al., 1959) and interferes with cell wall formation 

 (Tomasz and Borek, 1959); 6-mercaptopurine affects acetate and formate 

 utilization, probably by interfering with the formation of purine containing 

 cofactors (Bolton and Mandel, 1957); 5-hydroxyuridine exerts several 

 different effects including inhibition of purine utilization (Slotnick et al., 

 1953); 8-azaguanine inhibits adenosine deaminase (Feigelson and David- 

 son, 1956); 6-azauracil causes the inhibition of polynucleotide phosphory- 

 lase (Skoda et al., 1959) and it blocks the conversion of orotic acid into 

 uracil (Skoda and Sorm, 1958, 1959; Sells, 1959-1960). Several analogues 

 can substitute for the natural parent constituent in the feed-back control 

 exerted by this compound upon its own synthesis (Gots and Gollub, 1959; 

 Trudinger and Cohen, 1956; Smith and Sullivan, 1960). 



Different types of cells also react differently or to various degrees to a 

 purine or pyrimidine analogue, and a type or effect which is shown in one 

 organism does not necessarily occur in others. Therefore the effect of an 

 analogue on a given organism cannot be predicted, and careful analysis is 



