262 Colchicine 



colchicine and to a "stress" releasing cortisone and other lymphocyte- 

 damaging hormones from the adrenals (Chapter 7) . It led to the idea 

 of treating lymphoid iimiors in C3H strain mice with colchicine. ^-^ 

 The malignant lynijjhocytes, like those of thymus and spleen, under- 

 went a pycnotic destruction after injections of 0.025 mg. repeated 

 every third day. The average duration of life of the animals after 

 the tumors had been grafted was significantly prolonged. In controls 

 it was 31.5 days; in those injected with colchicine, 50.5 days. Histo- 

 logical study sho^ved that the reticidum cells and some of the neo- 

 plastic hiiiphocytes escaped destruction, and resumed growth when 

 the injections were interrupted. In another series of experiments'^ a 

 permanent regression of the 6C3HED lymphosarcoma (in C3H mice) 

 was obtained by daily injections of 0.5 to 0.75 mg/kg after the tumor 

 had reached a diameter of about 1 cm. The animals cured from the 

 grafted neoplasm became immune to further graftings of the same 

 tumor. No similar effects were observed after cortisone. This ap- 

 pears to rule out the jjossibility of colchicine acting on tumor growth 

 by the indirect pathway of the pituitary-adrenal system. In these 

 lymphoid tumors, colchicine destroyed the cells and their mitoses, 

 and no mention is made of hemorrhage playing any part in the 

 chemotherapeutic action.^''' ^ 



In epithelial tumors the results vary considerably. For instance, 

 the Brown-Pearce carcinoma of the rabbit showed some increase in 

 the percentage of metaphases after 1 mg/kg of colchicine. The re- 

 sponse was, however, so unpredictable as not to warrant further 

 study.-"'' Some authors have reported an important prolongation of 

 life in mice bearing the Ehrlich carcinoma,^" ^^'hile in various other 

 timiors of mice and rats no such jjrolongation could be claimed. "'-• *'^- '^^ 



Studies on virus-induced malignant growths in fowl are of in- 

 terest. In animals grafted with the Rous sarcoma, doses capable of 

 arresting the testicular mitoses did not modify the tumor growth. 

 Larger doses killed the lairds. ^*'' In avian erythroblastosis, a dose of 1 

 mg/kg injected over a jjeriod of five days did not alter the evolution 

 of the malignant growth of blood cells.''- Some inhibition of the 

 growth of the Rous viius has, however, been observed, ^^ especially 

 when this is cultivated on the chorioallantoic membrane of eggs. 



It appears that considerable variations in sensitivity towards colchi- 

 cine exist from one tumor to another,^^' '*'^ and that the toxicity of 

 the drug has often limited its use. Further work should clearly be 

 aimed at many different tiunors and at the use of the new colchicine 

 derivatives, which are discussed in Chapter 17. 



/0.3-5; The Sliope pajjilhjjna in rahhits. This is a virus-induced 

 tumor, which is very widespread in this species. A closely related 

 virus, myxomatosis, has even been advocated as a tool for the ex- 

 termination of rabbits in Australia and other countries. This tumor 



