412 Colchicine 



SH groups in the spindle.""' This hypothesis was in agreement with a 

 theory of spindle activity in which reversible changes of SH to S-S 

 functions were supposed to play a prominent part in the "contractile" 

 properties of the spindle. The further discovery that -SH substances 

 themselves were also sjiindle poisons, for instance, dimercaptopro- 

 panol and sodium dielliyldilJiiucarbainale, was in agreement with this 



CH — SH 

 yCHg I 



y/ CH SH 



0=AS CH3 I 



\ CHOH 



^O — N a 

 (XIII) (XIV) 



hypothesis, if it was considered that a proper equilibrium l^etwcen 

 reduced and oxydized sulfhydryl functions was indispensable for 

 spindle activity.-^" 



This theory of chemical action on the spindle received further sup- 

 port from the discovery that many metals, known to combine with 

 -SH groups, are mitotic poisons.'^" Ethylmercurychloride is an ex- 

 ample of an organic poison of this type, active on plant cells, ■■^•'' ''" 

 while cadiniuiu salts are most effective in arresting mitosis in mam- 

 mals. 122, 30, 2 -fhe inhibition of metaphase by beyyUium salts, which 

 has been considered to be the result of nuclear phosphatase inhibi- 

 tion,i" may possibly be explained by the combination of this metal 

 with sulfhydryl groups. 



It has been further demonstrated by work on tissue cultures and 

 in injected mice, that the typical -SH poisons, chloracetopheyione, 

 iodoacetic add, and iodoacetajnide, arrested mitoses at metaphase.^^"- 

 50 However, these substances are very toxic, and have strong inhibi- 

 tory actions on glycolysis, which may be important in explaining 

 their action on cell division. Some of the complex molecules con- 

 sidered in the next Subsection may also act as -SH poisons. 



This does not close the list of mitotic poisons which appear to act 

 chemically on the cells. The most remarkable is etJiylcaibylaminc 

 (C.H-.CN) , which has been demonstrated to modify the course of 

 mitosis in tissue cultures exactly like colchicine. 1-" Total inactivation 

 of the spindle with exploded metaphase and, later, formation of 

 numerous micronuclei were conspicuous. Ethylcarbylamine reacts 

 chemically with metals; this chelating property is shared by diethyldi- 

 thiocarbaiuaie, another spindle poison.'"' These results point to some 

 further complexities of the problem; the action of other organic 

 spindle poisons will show how far we are from understanding the 

 basic changes involved. 



