260 Colchicine 



to malignant growth, and which may end in leukemia, the increase 

 of metaphases of bone-marrow cells explanted /?? vitro in a solution 

 of colchicine was found not to differ from normal.'' The striking re- 

 sults obtained with marrow of patients with acute leukemia have 

 been mentioned in Section 10.1.^ 



10.3: Cancer Chemotherapy 



It is evident that the data on the growth of neoplastic cells treated 

 with colchicine are meagre. Workers were quickly attracted by the 

 false idea of finding a cancer cure, and they injected colchicine into 

 animals bearing various timiors. Botanists, also, painted plant timiors 

 with colchicine. Neither were much interested in the fundamental 

 changes taking place. As a result, the cytological data are often in- 

 complete and only mention "cellular destruction," "nuclear frag- 

 mentation," or "tumor necrosis and hemorrhage." This emphasis on 

 the gross changes in animal tumors has led to a neglect of the funda- 

 mental problem which is at the base of any cancer chemotherapy: 

 Are malignant cells more severely damaged than normal ones? This 

 is of great importance with a chemical like colchicine which affects 

 all types of mitoses. The appearance of large zones of hemorrhage 

 in tumors treated with colchicine has led some workers^' ■*'^' '^'^ to the 

 conclusion that this is the main action of the drug and the only 

 possibility of obtaining a destruction of the neoplastic growth. This 

 problem will be discussed first, though it is quite evident to all en- 

 gaged in cancer chemotherapy that a drug the main action of which 

 would be hemorrhagic destruction, is of no use in medicine. 



lo.^-i: The hemorrhagic effect and metabolic changes. Many re- 

 ports on experimental tumors in mammals, whether induced by car- 

 cinogens or grafted, showed that colchicine was unable to prevent the 

 neoplastic giowth.^^. c6. is, os j^ the sarcoma 180 of the rat even the 

 largest tolerated doses were unable to arrest all mitoses at meta- 

 phase.i^ From the unaffected ana- and telophases the malignant 

 growth resumed its activity once colchicine was discontinued. 



On the other hand, the metabolic changes in tumors treated by 

 colchicine were being investigated. In grafted tumors in rats the 

 metabolism, measured /'// vitro, was found to decrease. At the same 

 time, the ascorbic acid content of the tumors was considerably lowered, 

 and large zones of hemorrhage were seen.^ This last change was be- 

 lieved to play a great part in the regression of the tumors. Similar 

 changes could be observed after the injection of Bacillus typhosus 

 extracts. It was not reported that these bacterial products induced 

 any nuclear or mitotic change.^ Similar hemorrhages were also noticed 

 in other grafted carcinomas, in spontaneous mammary tumors, and 

 in methylcholanthrene-induced tumors of mice. They were most ap- 

 parent 18 to 20 hours after colchicine. The spontaneous tumors ap- 



