298 NUCLEIC ACIDS AND GROWTH 3 



of Stimulating effects of RNA or nucleoproteins on the regeneration of planarians 

 (Brondsted and Brondsted, 1953) and on the growth of tissue cuhures (Kutsky, 

 1953; Maganini et al., 1953). But very little is known about the possible existence 

 of natural inhibitors of growth, acting on the nucleic-acid system. 



One possible factor for such a role is obviously ribonuclease, since we already know 

 that this enzyme inhibits mitosis and stops growth in many biological systems: 

 onion roots (Kaufmann and Das, 1954, 1955; Brachet, 1954a, 1955b), amoebae 

 (Brachet, 1955c), tumour cells (Ledoux and Baltus, 1954; Ledoux, 1955a, 1955b; 

 Ledoux and Revell, 1955), amphibian eggs (Brachet and Ledoux, 1955), tissue 

 cultures of fibroblasts (Chevremont and Chevremont-Comhaire, 1955). Unfortu- 

 nately, very little is known about ribonuclease concentration and activity in resting 

 and growing cells, a question which deserves a thorough study. Estimations of the 

 ribonuclease content of developing frog eggs (Finamore, 1955, and unpublished 

 personal observations) do not indicate great changes in ribonuclease content during 

 development; but no conclusion can be drawn until more is known about the 

 state of activity in which the enzyme is present within the cell. Such a warning 

 is especially necessary in view of the recent report by Roth (1955) of the existence 

 of a natural ribonuclease inhibitor in liver. 



One could also speculate about deoxyribonuclease as a natural growth regula- 

 tor: but the investigations of Allfrey and Mirsky (1952) indicate that the function 

 of this enzyme is not limited to some simple role in cell division. Furthermore, 

 according to Allfrey and Mirsky (1952), the bulk of the enzyme is located in the 

 cytoplasm, and not in the nucleus where DNA is localized. It is interesting, how- 

 ever, that the deoxyribonuclease content of liver cells is strongly dependent on the 

 physiological conditions: the enzyme concentration more than doubles on severe 

 fasting. 



Another possibility is that the activity of the nucleic acids might be inhibited by 

 basic proteins, such as the normally occurring protamines and histones. Recent 

 work by Fischer and Wagner (1954) and Fischer and Brandis (1954) lends some 

 support to this contention : they found that protamines and histones readily pene- 

 trate into many living cells and that they inhibit the multiplication of phage 

 Tj. Inhibitory effects on cell division (Kaufmann and Das, 1955), growth and 

 protein synthesis (Brachet, 1955b) have also been reported for living onion root- 

 tips and cancer cells (Zbarskic and Perovschchikova, 1954). It has recently been 

 suggested by Mirsky ( 1 956) that the well-known replacement of histones by pro- 

 tamines during spermatogenesis may be the reason for the genetic inactivity of 

 mature sperm. 



Obviously, much more experimental work is needed before the existence and 

 the role of normal inhibitors of nucleic acid metabolism are proved; the problem 

 might, however, well be of the utmost importance for an vmderstanding of normal 

 and malignant growth. 1 



^ The author wishes to thank Dr. J. B. Solomon, who considerably improved the text of 

 the present Chapter. 



