Neoplastic Growths 261 



peared the most resistant towards this new "colchicine-efTcct." A 

 parallel decrease in ascorbic acid content, respiration, and glycolysis 

 was obscr\'ed.^ 



The significance of these hemorrhages, which appear only with 

 sublethal doses,- is not clear. It has been suggested that mitotic 

 poisoning of the endothelial cells of the tumor capillary bed (cf. 

 Chapter 9) may play an important part.**" Escherichia coli filtrates 

 have similar hemorrhagic proj^erties, and add their eftect to those of 

 colchicine, but the over-all toxicity is also increased. The polysac- 

 charide extracted from Serrdtia inarcescens is interesting, for it also 

 produces hemorrhages in timiors and has been shown to interfere 

 with cell division."" 



Tumors treated with colchicine become quite fragile. In the Flex- 

 ner-Jobling carcinoma of rats the injection of distilled water in the 

 tumor has a destructive action 15 hours after colchicine. These ex- 

 periments, which were done on a great number of animals, have been 

 reported only in a short note.'^*' 



In a recent review,'*' the effects of colchicine on 17 different strains 

 of tumors and 49 spontaneous mammary carcinomas in mice have 

 been sunnnarized. AVliile the effects vary according to age, genetic 

 constitution, rate of tumor growth, toxicity of colchicine, and histo- 

 logical structure, the hemorrhagic effect was considered to be the main 

 factor in tumor regression. In highly cellular and soft tumors grow- 

 ing on RIII mice, complete cures were reported. Regression is ob- 

 tained only by doses very close to the lethal one and far above those 

 that simply arrest mitosis. Soft and rapidly growing tumors respond 

 well, while slowly growing and fibrous tumors are resistant. 



This conclusion applies only to the experience of one group of 

 authors, and instances can be found of malignant growths which re- 

 spond to colchicine without any hemorrhage. Such is the case of a 

 benzopyrene-induced sarcoma (HL tumor) in albino rats." The re- 

 gression appeared here to bear some relation to a decrease in the 

 pyrophosphatase of the neoplasm, while liver and kidney pyrophos- 

 phatase were not affected. 



Further exam])les will be given of favorable effects unrelated to 

 hemorrhage, which is clearly related to verv toxic doses and is of no 

 practical interest in chemotherapy. The hemorrhagic effect is one 

 more of the riddles of colchicine, but to insist too much on it as the 

 main mode of action of the drug on tumors is to discourage any 

 further work on nontoxic derivati\es Avith mitosis-arresting jiroper- 

 ties. 



70.5-2.- Auinitil tinnors. One of the most striking effects of colchi- 

 cine noticed in the first experiments on animals44 was the destruction 

 of lymphoid and thymic cells following the metaphase arrest of their 

 mitoses. This action is certainly related to the general toxicitv of 



