Mechanism of Colchicine-Mitosis 403 



fibrous structvires disappear and later between the poles and the cen- 

 tromeres, where ihcy bring about a shortening of the fibers. The 

 biochemical basis ot this complex mechanism is unknown. The 

 chemical constitution ot the fibers themselves has not been deter- 

 mined, with the exception of some histochemical Avork indicating 

 that their proteins are rich in sulfhydryl groups (cf. Subsection 

 17.4-2). 



Any theory linking "narcosis" to spindle changes requires ad- 

 ditional investigations with a wider use of specimens from both ani- 

 mals and plants. The Swedish author Ostergren"' -♦- has presented 

 evidence for the "narcosis theory" using AUiuni root tip cells as a 

 major testing material. The relationship demonstrated to exist be- 

 tween lipo-solubility and the c-mitotic activity for many substances 

 fits the hvpothesis quite well, but there are unanswered questions that 

 do not give us as much supporting evidence as everyone woidd desire. 

 Therefore, the hypothesis put forward by Ostergren at this time re- 

 cpiires additional testing. Rejjcating from the preceding paragraph, 

 it is to be stressed that the lack of specific biochemical evidence 

 drastically limits our understanding, particularly when trying to 

 formulate basic mechanisms for reactions such as the c-mitosis. 



Colchicine is a spindle poison with a low thermodynamic activity 

 and extremely high solubility in water. Therefore, this chemical is an 

 exception to the general rule that applies to simpler aromatic deriva- 

 tives.^i These relationships are clearly illustrated in Figure 17.2, as 

 drawn from experiments with cells of Allium and/or Triticnm. The 

 proposed theory of a narcosis, while interesting from the standpoint 

 of the biochemistry of the spindle, cannot at the same time apply to 

 colchicine, "which aj^pears to act on a chemical basis rather than 

 physically. This conclusion was reached independently by the French 

 authors.^^ Certain results will now be considered to show that ideas 

 of a chemical relation between alkaloid and spindle appear promising 

 for the ultimate explanation as to how a c-mitosis is accomplished. 



17.4: Chemical Action 



Two lines of research indicate that s])indle poisoning may be re- 

 lated to definite chemical structures, and probably to chemical inter- 

 ference between pcjisons and spindle fibers. The first is the study of 

 derivatives of colchicine and related molecules. This indicates that 

 minor changes in this complex atomic structure may considerably 

 affect the cytological activity. The second is the study of other mitotic 

 poisons: while those Avhich have been considered so far acted more 

 physically than chemically, there is a small but imjiortant group of 

 substances which inactivate the spindle and which possess specific 



