394 Colchicine 



tion. This is especially visible in plant cells, where the general toxic 

 reactions of strong closes described in animals (Chapter 7) are 

 avoided. No other spindle poison is at the same time so active and 

 so efficient, though some of the colchicine derivatives may poison 

 animal spindles at concentrations lower than colchicineJi- "• ^•^' »-• ^'^ 



The changes of the mitotic spindles under the action of colchicine 

 have been described at length in Chapter 3. Suffice it to recall here 

 that the fibrous and polarized spindle is very rapidly changed into 

 an amorphous "pseudo-spindle" or "hyaline globule," which is in- 

 capable of moving the chromosomes.-*"- ^^ Much evidence is at hand 

 to demonstrate that the action of the alkaloid is proportional to its 

 concentration and is totally reversible, two facts of great importance 

 in the interpretation at a molecular level of spindle inactivation. 

 Chromosome changes are usually only a consequence of the arrest of 

 mitosis, especially in warm-blooded animals. In plants, the continua- 

 tion of the normal chromosome-cycle in cells devoid of spindles is 

 the basis of colchicine polyploidy. Cytoplasmic changes have been 

 recorded in plants and animals, especially a decrease in the general 

 viscosity, or rigidity, as evidenced by centrifugation.^s This may be 

 a consequence, and not the cause, of spindle inactivation. 



Most of the other cellular changes are indirect consequences of 

 the spindle inhibition. Short and thick chromosomes are frequently 

 met in arrested metaphases. In plant cells, the cycle of chromosome 

 reduplication is not disturbed by the alkaloid, while in animals, only 

 a few instances of polyploid cells resulting from the multiplication 

 of chromosomes in colchicine-treated cells have been recorded. Here, 

 the prolongation of metaphase leads often to degenerative nuclear 

 changes. Alodifications in the shape of cells and in the growth of cell 

 membranes have been recorded (cf. Chapter 4) . These involve fi- 

 brous proteins, and may be of a similar nature to the spindle changes. 



Considering the many data that have been gathered, it can be 

 stated here that colchicine appears to be one of the most specific and 

 least toxic of all the spindle poisons. Hence, any work which helps 

 to solve the problem of spindle inactivation by this complex mole- 

 cule may throw more light on the mechanism of cell division and 

 on the physiology of the peculiar fibrous protein which constitutes 

 the sjMndle. The importance of this cannot be underestimated, for 

 all cellular growth in nucleated cells involves the separation of the 

 two groups of chromosomes by the fibrous strands of the spindle.* 



* Whether similar mechanisms exist in bacteria is still open to discussion, 

 though nuclei ha\e been recognized bv many authors, and at least one group has 

 tentatively identified a mitotic spindle.-* It may be that tiie plurinucleated bac- 

 terial forms which arise under the influence of some antibiotics, e.g. penicilhn, are 

 true polyploid cells. Some antibiotics have been shown to be spindle poisons ni 

 warm-blooded animals,^ and future work may lead to the extension of the concept 

 of mitotic poisoning to microorganisms. 



