68 Colchicine 



3.2: Spindle Inhibition 



Every mitotic cycle builds anew the spindle fibers. Cytoplasmic 

 separation, a function of cytokinesis, is closely coordinated with the 

 fiber and spindle functions.-'* Colchicine prevents the formation of a 

 sjjindle at jMojihase, jjrecludes a nuclear mitosis, delays chromosomal 

 separation, inhibits daughter nuclei, and effectively blocks cleavage 

 processes. 



Among plants, the inhibition starts at the polar cap stage when 

 polarity makes an appearance.-*'' The first sign that colchicine acts 

 ujjon a spindle is noticed at the ])olar cap stage. ••^' Among animals, 

 the preliminary spindle inhibition is an interference with the de\elop- 

 ment of the astral rays, and functioning of the centriole outside the 

 nucleus.^ The initial inhibiting inHuence is seen at the time nuclear 

 membranes are about to disappear and the centrioles begin their 

 movement. 



The prophase orientation of chromosomes in animal cells may 

 or may not be destroyed by colchicine. Likewise, i)lant cells, e.g. in 

 Dipcadi, have a prophase orientation that is determined from the pre- 

 vious telophase. These arrangements are not disturbed by colchicine. 

 Thus, colchicine may inhibit the spindle without changing a basic 

 chromosomal arrangement at prophase, •''•'' although strong solutions 

 may interfere with the orientation before membranes disappear. 



The bipolar mitosis is effectively pre\ented by colchicine acting at 

 late prophase, and progressive changes from interphase into prophase 

 are not inhibited by colchicine. 



Undoubtedly there is an action upon resting cells if strong con- 

 centrations are used.'-^- ''^ Nuclear poisoning,^- intranuclear precipi- 

 tates,*'* chromatin condensation, *•"• pycnotic destruction,-'^- -^i- -* and 

 nuclear degeneration'"'" before mitotic arrest, are possible actions of 

 colchicine. Deeply stained inclusions in cells of Amphibia were ob- 

 served after strong treatments.*^'' In most cases concentrations abo\e 

 the threshold for c-mitosis induce the changes. Neuroblastic cells of 

 grasshopper, usually very responsive at prophase, metajjhase, and ana- 

 phase, recjuire a tremendous concentration (1000 X '*^ *' ^^^) 'i^ inter- 

 jjhase or late telophase.-'' 



The mitotic stage at which colchicine is most effective in lowest 

 concentration, is late prophase. Ihere is no doubt that colchicine 

 interferes with transformations of karyolymph, because the regular 

 linear arrangements of fibers do not develop. These structures nor- 

 mally are formed 20 mimites after disapj^earance of the nuclear mem- 

 i)rane; but in the presence of colchicine, fibers do not form. Instead, 

 there is formed a hyaline globule in grasshopper neuroblastic cells, 

 which is nonfibrous. 



