398 Colchicine 



jy.2-2: Resistance in plants and animals. Cells of Colcliinnn 

 aatumnale L. yield as much as four parts per thousand of alkaloid. 

 Thus, some of the mitoses of the plant may be in close relation to 

 large doses of colchicine, and the questions arose by what mechanism 

 these mitoses are protected, and whether c-mitosis is possible in Col- 

 chicum. The first experimenters used as a test the bulbous enlarge- 

 ments of the root tips of Colchicum and concluded that large doses 

 of colchicine were active. However, as mentioned in Chapter 4, this 

 is only presumptive evidence, and c-tumors may arise -without any 

 mitoses taking place (C:hapter 4) . Cytological work was carried fur- 

 ther on several species of Colchicum and with various concentrations 

 of the alkaloid.-o xhe results were compared to those of the spindle 

 poison, acenaphthene (cf. Subsection 17.3-2). No true resistance in 

 excised root tips grown on agar with strong concentrations of colchi- 

 cine-o was observed, though the concentration of alkaloid necessary to 

 induce full c-mitosis was considerable (5 per cent in water) . The 

 possible influence of the chloroform present in crystalline colchicine 

 has been ruled out; chloroform is only a weak spindle poison.^ i' It 

 is clear that mitoses in Colchicum are considerably more resistant 

 than any other plant mitoses towards the alkaloid. This type of re- 

 sistance appears somewhat similar to that of venomous animals to- 

 wards their own venom, but in the case of the plant, the basic mechan- 

 ism is not understood and further research would be useful. Evi- 

 dently, this is linked with the other unsolved problems of the role 

 and metabolism of colchicine in Colchicum sp. The glucoside found 

 in the plant, colchicoside,^- may be of some significance (cf. Subsec- 

 tion 17.4-1) . 



During routine laboratory tests the discovery was made that golden 

 hamsters resist very large doses of colchicine,"" considerably greater 

 than the lethal doses for rabbits, guinea pigs, mice, and rats. The 

 tests yielded no c-mitotic values, but only toxicity values which j^roved 

 beyond doubt that natural resistance exists with the hamsters. Another 

 similar case is the resistance of rabl)its to aconite. 



Hamsters are native to the region where species of Colchicum are 

 abundant (cf. Chapter 1). Through a long period of evolution the 

 hamsters may, by the processes of survival of those animals that lived 

 after eating the Colchicum, have passed this resistance on to succeed- 

 ing generations. Any part of the Colchicum, leaf, flower, seed, fruit, 

 corm, would contribute generous portions of colchicine that would 

 be lethal to an animal without resistance. 



Such resistance displayed by the hamsters is of interest in con- 

 nection with the evolutionary problems involved. Further \\'o\\ should 

 be done with the mitotic processes to make comparison of the action 

 of colchicine upon these features. 



