Mechanism of Colchicine-Mitosis 411 



poisons ot very different chemical structure, and indicating relations 

 between this structure and their action, throw further light on the 

 subject of spindle inactivation. 



ij.-f-2: Sulfhydryl poisons. \Vith a few exceptions, most of the 

 work in this field has been done on tissue cultures^^ or in intact 

 warm-blooded animals.^^^^ This method has an advantage in that, be- 



TABLE 17.3 

 Smallest Antimitotic Doses (fig/ml) Effective in Arresting 

 Mitoses in Cultures of Chick Fibroblasts 

 (After Lettre «") 



Derivative Dose 



Colchiceine 5.0 



Colchicine 0.01 



Colchicamide 0.01 



jV-methylcolchicamide . 0025 



A'-ethylcolchicamide 0.003 



JV-propylcolchicamide . 08 



.\ -butylcolchicamide 0.9 



.Y-methyl-propyl-colchicamide 0.5 



cause of the necessity for avoiding toxic side-effects, only small doses 

 may be used. Hence, substances acting as narcotics or producing a 

 "physical" change ot the spindle will not be found to have mitotic- 

 poisoning properties. 



The most extensively studied in mammals,''^'- -»• ~^' ^" in inverte- 

 brates,-*'' on tissue cultures,'^' i-^' ''^ and in plant cells'**- -- are simple 

 derivatives of arsenic. Arsenious oxide and sodium nrsenite arrest 

 metaphase by destroying the spindle, and these star metaphases are 

 very similar to those described in Chapter 2. The most effective of the 

 organic arsenicals appears to be sodium cacodylate, or dimeihylarsin- 

 ate (XIII). 



In mice, it has been demonstrated that this action was reversible, 

 that is to say, that arrested metaphases could be detoxicated and pro- 

 ceed to a normal telophase."'*' The inactivation of the spindle is thus 

 the consequence of a labile combination of its proteins with arsenic. 

 The detoxicating agent was dimercaptopropanol (BAL, British Anti- 

 Lewisite) (XIV) , a substance which combines rajMdly and strongly 

 with arsenic and other metals. This action of a chemical with two 

 -SH functions suggested that arsenic may have combined \vith similar 



