402 Colchicine 



None of these substances, however, has an activity comparable to that 

 of colchicine, and their mitotic effects are only visible in relatively 

 concentrated solutions. 



These facts, demonstrating that no evident relation exists between 

 the chemical constitution and the c-mitotic action, and that lipoid 

 solubility is always present, confirm the theory of c-mitosis as a nar- 

 cotized mitosis. Lipoid solubility is one of the foundations of Over- 

 ton's well-known theory of narcosis in animals. The wide use of gase- 

 ous narcosis in medical practice prompted some workers to study this 

 group of narcotics on the root tips of Allium cepa. These were kept 

 humid in a mixture of atmospheric air and the gases, which were 

 under pressure. Propane, nitrogen, nitrous oxide, methane, argon 

 (under a pressure of 75 atmospheres) , and hydrogen (200 atmos- 

 pheres) induced c-mitosis and typical c-tumors. However, only pro- 

 pane, nitrogen, and nitrous oxide induced polyploid cells, for the 

 other gases depressed too much the number of new mitoses.-^'' This 

 observation of c-mitosis under the influence of an inert gas like argon 

 definitely demonstrates that the chemical structure may be cjuite in- 

 different to the production of inactive spindles, and that physical 

 changes j)lay a great part. C-mitosis appears at this jjoint to be a 

 general reaction of the spindle under the most varied conditions. 

 Work discussed further will show how far these results may explain 

 the action of colchicine. 



17.3-4: Narcosis and colchicine. The facts gathered so far point 

 towards a close relation between metaphasic (spindle) poisoning and 

 lipoid solubility or thermodynamic activity. The precise relation be- 

 tween lipoids and the function of the spindle is by no means clear, 

 and narcotics appears to modify mitosis somewhat like cokH or high 

 hydrostatic pressure.^"* It is not surprising that the problem appears 

 complex, for very little is known about the main target of all these 

 poisons, namely, the spindle. That it is fibrous and anisotropic is 

 evident and is no longer discussed. ii"' ^o How it functions is the sub- 

 ject of much controversy, for it is not yet demonstrated whether the 

 fibers "ptUl" the chromosomes towards the poles (after gathering 

 them at the equator of the cell) , or if the chromosomes are "pushed" 

 polewards by a "Stemmkorper" lying at anaphase in the center of the 

 cell. The results of colchicine research indicate (Chapter 2) that trac- 

 tion must play an important role in the movements of the anaphase 

 plates, but how this traction takes place and on what sujjport the fibers 

 are anchored are still unsolved problems. The shortening of the 

 fibers involves most probably changes from fibrous to globular pro- 

 teins, as evidenced by the polari/ed light data.'^i These changes 

 probably take place first between the two anajihasic plates, where all 



