THE MITOTIC CYCLE 



energy is depressed, and respiration is stimulated at the same time 

 (McElroy^^*). It is therefore clear that these substances affect cell 

 division only indirectly by interfering with the energy supply at chem- 

 ical levels below that at which the various visible events of the mitotic 

 process are maintained. Again, d-usnic acid inhibits both cleavage and 

 the uptake of P^^, without any stimulus to respiration (Marshak and 

 Harting;^®^ Marshak^ '''^). This substance must block metabolic path- 

 ways at a point different from that affected by the substituted phenols. 



It is thus possible to interrupt cell division at a particular phase by 

 agents which act in different ways. For instance, cleavage in the sea- 

 urchin egg is inhibited by high pressure in a direct effect on the egg 

 cortex,* and by dinitrophenols which cut off the supply of energy to the 

 gelating egg proteins. In the absence of evidence from elsewhere, it may 

 not be possible to decide at what levels a 'mitotic poison' is exerting its 

 effect, even if the action is specific on one particular phase of division, 

 for energy requirements may be particularly high in a certain cell at 

 this point. Here is perhaps the most awkward complication of all for 

 those who wish to analyse the nature of mitosis through the experi- 

 mental treatment of dividing cells. 



The best hope of progress in the face of this difficulty is probably to 

 work systematically through a number of substances with definite 

 effects on mitosis, and to test their effects on other features of the activity 

 of the cell. A valuable observation of this kind has been made by 

 Zeuthen^^^ who has shown that suppression by colchicine of the 

 achromatic cycle and cleavage in the sea-urchin egg does not abolish 

 the normal waves in the curve of oxygen uptake, measured on the 

 Cartesian diver microrespirometer. These must therefore be related 

 to the nuclear cycle, for the formation of the chromosomes and their 

 reconstruction into nuclei continues in the egg treated with colchicine. 

 It is possible that the uptake of P^^ continues in these circumstances ; 

 Skipper et alii^^^ have recently shown that the incorporation of formate 

 carbon into nucleic acid purines in the mouse is unaffected by the 

 injection of colchicine. It would not be difficult to suggest a series of 

 such possible lines of inquiry, but to pursue them would need a large 

 amount of co-operation between experts in different techniques. 



* The remarkable action of threshold doses of podophyllin in causing regression of the 

 cleavage furrow in sea-urchin eggs in which division is already nearly complete is presum- 

 ably also a direct effect on the cortical gel (Cornman and Cornman-*''') . 



REFERENCES 



Nature of the stimulus to mitosis 



^ Hammett, F. S., Amer. J. Roentgenol., 43 (1940), 266 



2 — , Scientia, 5 (1946), 93 



^ Cunningham, B. and Kirk, P. L., J. Cell. Comp. Physiol., 20 (1942), 343 



200 



