INTERVENTION OF RNA IN LIVING CELLS 41 



decrease in the total RNA content. In fact, this complex breaks down 

 spontaneously when the eggs are simply washed and left in normal 

 sea water. After a few hours, basophilia (after freeze-substitution) 

 and incorporation of amino acids into proteins simultaneously 

 return to normal. 



A somewhat different mode of action is found for ribonuclease 

 in the case of ascites tumor cells (Ledoux and Baltus, 1954; Ledoux 

 and Revell, 1955; Ledoux et aL, 1956; Ledoux and Vanderhaeghe, 

 1956; Pileri et ah, 1959). The enzyme penetrates by pinocytosis 

 into these cells in the same way as into the amoebae; but it induces 

 an increased synthesis of RNA as an initial stage. This newly syn- 

 thesized RNA is apparently abnormal in nature, since its compo- 

 sition in bases differs from that of the initial RNA. As a result, in- 

 corporation of amino acids into proteins is already inhibited during 

 this first synthetic phase. Later on, the RNA content considerably 

 decreases and the cells finally break down. Many free nuclei are 

 found at the time in the ascites fluid. These interesting results of 

 Ledoux and his co-workers are of obvious importance for the 

 chemotherapy of cancer. It is clear that if growth is linked to pro- 

 tein synthesis and RNA metabolism, ribonuclease would be expected 

 to inhibit the growth of tumors, provided that the enzyme can 

 penetrate into the cancer cells. This has frequently been found to 

 be the case by Ledoux (1955a, b), who claims that the survival time 

 of tumor-bearing mice is significantly increased when they are in- 

 jected intraperitoneally with ribonuclease. 



The strong antimitotic activity of ribonuclease, which was first 

 discovered by Kaufmann and Das (1955) for onion root-tips, has 

 been confirmed for amphibian eggs (Ledoux et ah, 1955; Brachet 

 and Ledoux, 1955) and for tissue cultures (Chevremont and Chevre- 

 mont-Comhaire, 1955). The results obtained with amphibian eggs 

 during cleavage will be discussed in the next chapter. 



Ribonuclease does not, of course, penetrate into a// cells (Brachet, 

 1955a). Algae, yeast cells, molds and ciliates are usually insensitive 

 to its action, probably because of lack of penetration through thick 

 membranes or rigid cortex, and the absence of pinocytosis. The 

 situation is more complex in the case of bacteria. In B. megatherium. 

 References p. 50/54 



