Cell Division 



111 



change in respiration associated with rhyth- 

 mic disappearance and regeneration of the 

 nuclear membrane persists (Zeuthen, '51). 

 The increase in respiration is therefore not 

 associated with chromosome movement or 

 cytokinesis but with some process occurring 

 before visible prophase. 



If eggs have the advantage of being easily 

 available in large numbers in the same 

 stage, they have the considerable drawback 

 of being full of storage material and equipped 

 to go on largely independently of the en- 

 vironment. Because of this they are not 

 very useful for the study of the metabolic 

 requirements of mitosis. 



A few years ago Medawar and Bullough 

 and Johnson (cf. Bullough, '52) found an 

 excellent material for physiological studies 

 on dividing cells in adult mammalian epi- 

 dermis, a tissue that can be cultured quite 

 easily. In a series of beautiful studies Bul- 

 lough has analyzed the metabolic conditions 

 for mitosis. He showed that in the epidermis 

 mitosis is directly proportional to the con- 

 centration of glucose and the oxygen ten- 

 sion. Glucose is metabolized through the 

 citric acid cycle. The inhibition of mitosis 

 by 2,4-dinitrophenol suggests that oxidative 

 phosphorylation is involved in the reactions 

 providing the energy for division. Any agent 

 that interferes with the citric acid cycle and 

 oxidative phosphorylation prevents mitosis. 

 These metabolic inhibitors affect the cell 

 only during the part of interphase preced- 

 ing mitosis, a stage which Bullough named 

 antephase. Once the cell has passed this 

 stage it can go on in the absence of respira- 

 tion. 



In other tissues mitosis occurs also in the 

 absence of respiration. Embryonic cells, for 

 instance, either in vivo or in vitro, can 

 divide without oxygen and are not inhibited 

 by respiratory poisons (Parker, Pomerat and 

 Willmer). These cells therefore may depend 

 on glycolysis alone for mitosis (Laser; O'Con- 

 nor). They are inhibited by fluoride and 

 iodoacetate (Hughes). (References in Bul- 

 lough, '52.) 



The observations on cultured epidermis 

 are corroborated by studies on intact mice 

 (Bullough, '52). The diurnal rhythm of mi- 

 tosis in several tissues of mice was shown 

 to be related to the deposition of glycogen 

 in the cells during rest. When the animals 

 are active the amount of carbohydrates avail- 

 able is decreased and the number of mitoses 

 goes down. Injection of carbohydrates and 

 phosphate raises the number of mitoses to a 

 maximum. Inhibition of phosphorylation by 



phloridzin, on the other hand, blocks division 

 completely. 



Though the biochemical analysis of mi- 

 tosis is still in its beginning, some generaliza- 

 tions are already possible. In order to divide, 

 the cell requires energy. This energy is de- 

 rived from breakdown of carbohydrates, 

 through glycolysis in some cells and respira- 

 tion in others. Oxidation of other foodstuffs 

 may also occur, especially in eggs. The 

 energy is then trapped in high-energy phos- 

 phate bonds. All this takes place in the 

 antephase, before any visible changes occur 



Fig. 23. Oxygen uptake and mitosis in consecutive 

 cleavages of Psammechinus. "Whole" nuclei indi- 

 cate interphase and prophase, "open" nuclei meta- 

 phase and anaphase. The increase in oxygen uptake 

 occurs before each division when the nuclei are 

 "whole." (After Zeuthen, '5L) 



in the cell. During this phase the "batteries" 

 of the cell are charged up and from then on 

 mitosis proceeds without further energy up- 

 take from the environment and only direct 

 interference with mitotic organelles, or death 

 of the cell, can block division. Further work 

 will have to show how these metabolic 

 processes of antephase are related to chro- 

 mosome reproduction, how the energy is 

 stored and made available for the various 

 reactions during actual division. 



MITOGENESIS 



What are the conditions, both internal and 

 external, that cause a cell to divide? And 

 what conditions are responsible for the cessa- 

 tion of cell reproduction? A free living cell 

 such as an amoeba grows until it reaches 

 a certain size and then it divides. A similar 

 relationship between size and mitosis is 

 found in other protozoans, the rate of divi- 

 sion under optimal conditions being char- 

 acteristic of a species. If the size of an 



