418 Colchicine 



awaited; they may help to understand better the biochemistry of the 

 spindle and the physiological functions of //?f'^o-inositol.-'^ As for the 

 action of y-hexachlorocyclopropanc, it may of course be of a "physi- 

 cal" type, similar to that of the numerous other c-mitotic and poly- 

 ploidizing substances studied in plants. ^^^ 



77.5-2; Other anlagonists and sy}iergists. In tissue cultures of 

 rabbit heart fibroblasts, 1-ascorbic acid was found to prevent, to a 

 certain extent, the action of colchicine.^^ The numbers of arrested 

 mitoses were smaller, and a careful study of the different types of 

 mitotic abnormalities indicated that the vitamin decreased the amount 

 of sjiindle inactivation. This was not the result of an action as a vita- 

 min, lor d-(iraboascorbic acid, whose properties as a vitamin are 20 

 times weaker, had the same effect. The two substances are equally 

 reducing, and the interpretation of these residts is difficult, lor ])- 

 qiiinone, an oxydant, also depressed colchicine inhibition of mi- 

 toses. ^^ An antagonism between colchicine and "soluble prontosil" 

 (sulfanilamide) has been reported in plants,'" but the effecti\e concen- 

 trations of the sulfa drug were about a hundred times those of col- 

 chicine, and solubility effects were unavoidable. In animals, sulfanil- 

 amide has been claimed to influence colchicine-leukocvtosis, but this 

 was only remotely related to mitosis^-' (cf. Chapter 7) . 



An extract from hearts of embryonic warm-blooded animals has 

 been reported to delay the cytotoxicity of colchicine in fibroblast and 

 myoblast cultures. A colchicine concentration of 2 X 10'^ ^^ ^^'^s with- 

 out effect after 10 hours in cultures previously treated Avith the ex- 

 tract. If this was added after the alkaloid, no antagonism was vis- 

 ible.i--^ Another more recent obser\ ation is that glycosidic substances 

 endowed with cardiotonic activity decrease the action of colchicine in 

 tissue cultures of chick heart fibroblasts. s'* 



It appears evident from these data that no true antagonism has 

 yet been found between any substance and colchicine, on a molar 

 basis, and that the only effects observed depend on the presence of 

 substances either of unknown chemical nature or in concentrated 

 solutions. 



On the contrary, the search for synergists of c-mitotic activity has 

 yielded important results.*^'"' -'^ Some synergists act mainly by increas- 

 ing cellular i:)ermeability to the alkaloid, and the reader is referred 

 to tlie paper of Deysson-'^ for a detailed study of this type of false 

 synergism. It has been observed only in plant cells. In fibroblast 

 cultures, Lettre has conducted a very large series of experiments, and 

 has discovered that many substances increased the action of colchi- 

 cine, though having no c-mitotic activity of their own. These syner- 

 gists belong to the most dissimilar groups of chemicals: alkaloids, 

 steroid hoimones, and carcinogenic agents (benzopyrene) . The 



