"^^caI 



CHAPTER 3 



Spindle and Cytoplasm 



3.1: Colchicine and Spindle Fibers 



More metaphases than anaphases or telophases collect in tissues 

 treated ■with colchicine, creating an inij^ression that chromosomes 

 appear stranded between the two poles. Obxiously colchicine blocks 

 the mechanism that regularly mo\ es them to the respective poles (Fig. 

 '5.1A,B) . Interference seems to be localized at the spindle fiber; con- 

 sequently, arrested metaphases pile up in greater numbers per given 

 area than do the other mitotic stages.-^' ^^- ^ 



A disproportion of metaphases was pictured b) Pernice in 1889. His 

 illustrations-"^' ^^ show many arrested metaphases with \ery few ana- 

 phases; the contact between the drug and intestinal cells of the dog 

 blocked mitosis (Fig. 1.4). 



If the spindle fiber is the substrate where colchicine acts — and 

 there are man\- data to support this assumption — then c\ tological and 

 biochemical methods shoidd show us more clearly what reactions 

 occur. The basic cause for a mitotic arrest undoubtedh is to be found 

 in the chemistry and physiology of the spindle fiber and attending 

 mechanisms. ^1 



Provisionally, let us say that colchicine alters rather than totally 

 destroys the spindle substance. Such assumjjtions are consistent with 

 cytological tests, ft is known that arrested metaphases fail to show 

 the usual spindle fibers as linear structures; therefore, conversion of 

 a fibriform element into a corpuscular one becomes a tempting sug- 

 gestion, with attractive possibilities for explaining, at one le\el, how 

 the spindle fiber and colchicine in teract.'-^- "'"• ^"- '■'•''■'-■ •^' 



Molecules of colchicine reacting with a molecular system ol sjjindle 

 substrate ha\e been considered as one of the basic relationships be- 

 tween the two substances^-^' ^^' '^^' '"'■ "" Such an explanation can be 

 given on a quantitative basis. The destruction or inhibition of the 

 fiber then appears to be a quantitative reaction, because the concen- 

 tration of colchicine is a critical factor. 



[65] 



