234 TORE HULTIN et al. 



state of the microsomal membranes for the functional abihties of the 

 attached RNP-particles. 



The stimulation effects described in the previous sections cannot yet 

 be properly interpreted. It has been shown, particularly by experiments 

 with regenerating liver, that growth stimulation may be accompanied by an 

 increase in the total amount of RNP-particles in the cytoplasm [2, 5]. 

 This process, by which the total capacity of the protein synthesizing 

 machinery rapidly increases, may, however, constitute a rather late link 

 in the reaction chain of growth stimulation, since, at least in regenerating 

 liver, it demands a fairly long induction period (12-14 hr.). There reason- 

 ably must be a demand for more direct regulation mechanisms, by which 

 the production of individual protein species can be adapted to current 

 needs in a more rapid and flexible way (cf. [30]). The anabolic capacity of 

 an average cell is probably not fully utilized under normal physiological 

 conditions. It seems very likely, therefore, that the early stages of growth 

 induction are characterized by an intensified utilization of the anabolic 

 units already available. 



The experiments described here may have some bearing on stimulation 

 effects of the latter kind. They all suggest that even in cell-free incorpora- 

 tion systems the protein-synthesizing units are not always working at full 

 speed. There apparently may still be room for some influence of modifying 

 factors. In the experiments which were described these factors were 

 physiological in the sense that they could be induced at will already in the 

 living cells by treatments in vivo with agents such as hormones, carcinogens 

 and, in the case of the sea urchin egg, the fertilizing sperm. There is some 

 indication that the effects are related to a facilitated release of labelled 

 proteins from the metabolic sites on the microsome particles. In view of 

 this it will be of importance to attain a more detailed knowledge about the 

 mechanisms by which this release is mediated. 



Summary 



Some experimental evidence has been collected in favour of the 

 possibility that factors which influence the protein metabolism in the 

 living cells may survive the disintegration of the cell structure and continue 

 to influence the anabolic activity of the RNP-particles even in cell-free 

 amino acid incorporation systems. Both negative and positive after-effects 

 of this kind are discussed. The negative effects are illustrated by the action 

 of certain liver poisons, including potent carcinogens. A treatment in vivo 

 with these agents reduces the activity of isolated liver microsomes in cell- 

 free incorporation systems. The effect is not entirely due to a direct and 

 irreversible damage to the RNP-particles of the microsomes. Apparently 



