396 Colchicine 



(2) A great amount of work on plant cells with a large series of 

 chemicals has indicated that the destruction of the spindle was most 

 closely related to physical properties such as solubility. Jn short, c- 

 mitosis appeared as a "narcotized" mitosis, and the theories of nar- 

 cosis explain many findings. It will be seen further whether colchi- 

 cine fits into such a theory (Subsection 17.3-5). 



(3) Work with a molecule as complex as colchicine benefits from 

 experiments with related chemicals having simpler structures. These 

 have clearly indicated which, in the molecule of colchicine, are the 

 groups necessary for the production of c-mitosis. Other substances 

 "that inactivate spindles and have definite chemical properties which 

 may explain their action, are of varied structure and range from the 

 simple inorganic arsenic salts to complex molecules, alkaloids, or anti- 

 biotics. Though no chemical explanation of spindle destruction by 

 all these substances can be given, the comparison of their structures 

 and activities with that of colchicine throws some light on the singular 

 properties of this alkaloid. 



(4) Another approach to the problem of colchicine and the 

 spindle is through the study of antagonists and synergists. Some of 

 the work done in this field has given rise to controversies, but it can- 

 not be ignored. It is evident that the discovery of a substance capable 

 of preventing colchicine from destroying mitotic spindles might at 

 least throw some more light on the biochemistry of the alkaloid and 

 the spindle and on the complex reaction which apparently takes place 

 between them. 



From all these studies, however scattered and incomplete they may 

 yet be, emerges an outline of a new cellular j)harmacology which 

 should ultimately not only explain why colchicine is a mitotic poison 

 but help, by what can properly be named a "biochemical dissection 

 of mitosis," to explain the mechanics of cell multiplication and of 

 growth. 



17.2: Metabolic Actions of Colchicine 



We will consider under this heading only the facts which help to 

 explain c-mitosis. Other properties of the alkaloid have been de- 

 scribed in Chapters 4 and 7. The resistance of some plants and ani- 

 mals to colchicine will be mentioned. While the mechanism of re- 

 sistance is very imperfectly understood, it may be related to the in- 

 Huence of the drug on cellular physiology. 



77.2-7.- Enzymes. The work done in this field has been conducted 

 with quite different purposes, some authors being interested in mi- 

 tosis, others in possible mechanisms of colchicine treatment of gout, 

 the origin of hemorrhages observed in malignant growths (Chapter 

 10) , or the formation of c-tumors in plants. 



