258 Colchicine 



in this field. The basic relationship bel^veen the action of colchicine 

 and abnormally proliferating plant cells remains unsolved. An in- 

 duced vascularization similar to that referred to in Chapter 4 may 

 be related to this problem, and would provide a promising new 

 approach. 



The combined action of colchicine and X-irradiation on animal 

 and plant materials has been studied in several laboratories. No 

 decisive results appear to have been obtained. Ho^vever, some re- 

 cent research indicating the action of irradiation on metaphasic 

 chromosomes, shows that this work is ^vell A\orth reviewing. 



All the studies on neoplastic cells point towards the same inescap- 

 able fact: Whereas colchicine, as a treatment for gout, may well have 

 been observed prior to 1934 to have some favorable action against 

 cancer, all the papers ^vhich connect both have been published since 

 1934. This clearly indicates the significance of the cytological work 

 published at that time by A. P. Dustin-^ and demonstrated at the 

 1936 Cancer Congress. 



10.2: Experimental Study of Neoplastic Cells 



Malignant cells, especially in animal tumors, often display "spon- 

 taneous" mitotic abnormalities. These have been compared to those 

 induced by colchicine, and it has been suggested that the cells were 

 under the influence of some mitotic poison acting like colchicine. ^9 

 It has been suggested that this may be lactic acid.'-* However, these 

 spindle disturbances often appear to be the consequence of more 

 deep-seated nuclear changes, closely related to the cause of malignancy 

 itself, and leading to chromosome breakages and rearrangements. In 

 early human carcinomas, however, it has been pointed out that the 

 spindle changes appeared first.^^ xhe behavior of such cells when 

 brought under the influence of colchicine is of great importance, for 

 it would be of value to determine whether a specific destruction of 

 malignant cells by a spindle poison is possible. 



The effect of colchicine on cancerous growths has been studied 

 either by injecting the animals with the drug, or by explanting the 

 abnormal cells in vitro and using the methods of tissue culture. This 

 last procedure has been followed with a mammary carcinoma''- and 

 a sarcomai* of the mouse, and with Ehrlich mouse carcinoma grooving 

 as an "ascites tumor" in the abdominal cavity.^"- ''^ Concentrations of 

 100 X iO'''M to 1.25 X 10-*^ M inhibit outgrowth from the explants 

 and arrest cell divisions. This efTect is still evident on carcinoma 

 cells at a concentration of 0.5 X lO'^A/. In culture containing ex- 

 plants of both tumor and embryonic kidney, the latter showed the 

 greatest cellular destruction following the mitotic arrest. Differences 

 of sensitivity between various strains of carcinomas were found, \vhile 

 the Crocker sarcoma showed fewer arrested metaphases.^' 



