Ill CELL GROWTH AND MULTIPLICATION 1 59 



that individual genes determine definite steps of biosyntheses such as formation 

 of certain enzymes. — 3. Characteristic changes of the nucleus parallel protein 

 synthesis. As a general rule, cells with high protein synthesis show large nucleoli 

 and increased RNA content. — 4. Tissues with high protein synthesis (such as 

 vividly growing, secreting, embryonic, regenerative, viable malignant, etc. cells) 

 are distinguished biochemically by a high RNA content, and morphologically 

 by a high content of basophilic, RNA-rich inclusions of the cytoplasm. It may be 

 briefly mentioned that the high RNA content characteristic of proliferating 

 malignant cells has been developed by the present author and his coworkers 

 (Bertalanffy and Bickis, 1956; Bertalanffy, Masin and Masin, 1958) into a clinical 

 miethod of cytological cancer diagnosis using fluorescence microscopy. — 5. The 

 intimate interaction between nucleus and cytoplasm is expressed by the fact that, 

 notwithstanding the controlling function of the nucleus, cytoplasmic changes 

 (increased RNA content and basophilia) appear to precede, at least morphologi- 

 cally, changes of the nucleus (pyknosis, pleomorphism, hyperchromasia, abnormal 

 mitoses, etc.) (Pirozynski and Bertalanffy, 1955; Bertalanffy, Masin and Masin, 

 1958). The DNA content of the nucleus remains constant even in many malignan- 

 cies and in advanced stages of cell degeneration where the content of the nucleus in 

 RNA, proteins, and other compounds has materially changed (Vendrely, 1955). 

 The nuclear control of the cytoplasm or perhaps rather the interaction and 

 balance between nuclear and cytoplasmic systems finds a quantitative expression 

 in the nucleocytoplasmic ratio. In a qualitative way, this is manifest in the increase 

 of cell size in haploid, diploid, tetraploid, etc. mutants. Quantitatively, the relation 

 between nucleus and cytoplasm (or cell size) follows the allometric equation 

 (p. 224ff.). As a rule, there is a constant relation of the nuclear volume to the 2/3 

 power of cell volume, that is, to cell surface (Sinnott and Trombetta, 1936; 

 Nozawa, 1940; Teissier, 1941) (Fig. 4). Pathological changes {e.g. Addison's 

 disease, heart atrophy: Linzbach, 1950; giant nuclei in malignant cells) are 

 connected with shifts of the normal nucleocytoplasmic ratio. 



{c) Energy sources of mitosis 



The question of how the energy requirement for mitosis is provided appears to 

 be unsettled at present. According to Warburg's classical theory (1926), the 

 energy expense for cell division is essentially yielded by processes of fermentation. 

 Growing tissues are characterized by high glycolysis and so under anaerobic 

 conditions show high lactic acid formation. In tumors the respiratory system is 

 damaged. Hence they are not capable of oxidizing the products of glycolysis and 

 have high lactic acid formation. On the other hand, their high glycolytic activity 

 permits infiltrative growth regardless of oxygen supply as is necessary for 

 normal cells. 



It appears that at present hardly a general rule can be stated [cf. the recent 

 discussion, Weinhouse, Warburg, Burk and Schade, 1956). Experiments with 

 fats and sugars labeled with radioactive carbon (Weinhouse, 1955) show that 

 tumor cells are capable of completely oxidizing these compounds to CO2 by 

 mechanisms corresponding to those in normal cells. 



Animal ova which present the simplest conditions, show all possible differences 



Literature p. 253 



