78 THE BIOSYNTHESIS OF PROTEINS 



proteins made during this restoration period are abnormal; catalase for 

 instance has an abnormal temperature coefficient (Chantrenne, in press). 

 Beside the lesion which blocks all protein synthesis, and which is easily 

 repaired by an early addition of guanosine, continued action of azaguanine 

 causes another type of lesions which do not affect the synthesis of all the 

 proteins equally. These secondary lesions develop rather slowly, but they 

 are also cured very slowly by guanosine. A closer study of RNA during 

 azaguanine inhibition and of its reversal by guanosine showed that an 

 increasing amount of azaguanine is incorporated into RNA 'irreversibly', 

 in this sense that it fails to be displaced by guanosine. Identification of this 

 fraction of RNA will eventually make it possible to locate the site of the 

 secondary lesions which affect differently the synthesis of the individual 

 proteins. The specificity of synthesis of the individual proteins depends 

 probably on the integrity of this fraction of RNA. 



However, this conclusion cannot be taken for certain at present, since 

 DNA also has been shown to take up some azaguanine (Smith and Mat- 

 thews, 1957; Mandel et ah, 1957). Although the amount incorporated into 

 DNA is very small as compared to RNA, it might be enough to explain the 

 specific effects on protein synthesis. 



In Bacillus cereus, the uptake of azaguanine into soluble RNA is rapid 

 and the degree of guanine replacement by azaguanine very high. This 

 rapidly leads to an almost complete inhibition of all protein synthesis. It is 

 only during the recovery caused by guanosine that differential effects on the 

 synthesis of individual proteins can be observed. In other systems which 

 are somewhat less sensitive to the guanine analogue, differential effects are 

 observed during the action of the drug. Thus Creaser (1955-56) noticed 

 that in a Staphylococcus azaguanine can inhibit the synthesis of ^-galacto- 

 sidase much more than that of catalase. Jeener et al. (1959) also observed 

 that within a well-chosen range of concentrations, azaguanine depresses 

 the synthesis of bacteriophage protein much more than that of bacterial 

 proteins in B. megaterinm. More recently Heyes (1959) reported that 

 azaguanine inhibits protein synthesis in roots of pea seedlings only 

 partially, and that the degree of inhibition is not the same for the four 

 individual enzymes which were studied. Disturbances of the development 

 of embryos (Waddington et al., 1955; Nishimara and Nimura, 1958; De 

 Vincentis, 1960) or of fern gametocyte (Hotta and Oswa, 1958; Hotta et al., 

 1959), or of tumour growth (Kidder et al, 1951 ; Mandel et al, 1954) might 

 be due to a more or less selective action of azaguanine upon the synthesis of 

 individual proteins at certain stages of development (O'Brien, 1959). In 

 other systems, general inhibition of protein synthesis prevails (Dutton et al, 

 1958). 



(c) Summing Up. It can be concluded from the foregoing that slight 

 modifications of RNA brought about in vivo by ribonuclease or by the 



