Neoplastic Growths 259 



The ascites tumor enables colchicine to be brought in direct con- 

 tact with the malignant cells in vivo. The tumor cells float freely in 

 the fluid which gradually fdls the abdominal cavity. It is possible, 

 simply bv pipetting cells hom the abdomen, to examine all the 

 changes brought about by the injection of colchicine. i^- ^"' ''•■ Growth 

 curves of the tumor indicate that on the average each cell divides 

 every 2 to 2i/o days. After an injection of colchicine, the jjcrcentage 

 of mitotic cells rises in 9i/o hours from 1.2 to 14.2. Thirteen hours 

 after injection, it reaches 18.2, and falls to 2.0 after 48 hours. From 

 these figures, the normal average duration of mitosis can be calcu- 

 lated as follows: 1.2x9.5/14.2^1.2x13/18.2 = 0.8 hours, or 48 



minutes. 



Scattered groups of chromosomes and micronuclei are observed 

 in the colchicine-treated tumor cells. ^i- •'' Resting (intermitotic) 

 nuclei are also affected; their chromatin network becomes coarser. ^^ 

 In sarcoma-bearing mice, a series of experiments was carried out to 

 determine whether administration of colchicine had any effect upon 

 subsecjuent growth of the tumor cultivated in vitro.^^ Clolchicine 

 (().()()4 to 0.06 mg.) was administered by subcutaneous or intravenous 

 injection, and fragments of sarcoma were removed for cultivation at 

 various intervals after treatment. The growth of tumor tissue in vitro, 

 obtained from an animal treated Avith colchicine, was inhibited to a 

 large extent. Colchicine arrested mitoses, both normal and neoplastic. 



In human malignant growth, colchicine has been found useful 

 for the study of cellular multiplication. In 1 1 patients injected with 

 1.5 to 4 mg. subcutaneously or intramuscularly, modification of tumor 

 mitoses Avere observed. ^^ Four other patients did not show any re- 

 sponse, a fact which is not surprising, the dose being kept relatively 

 small by comparison with doses administered in animal work, because 

 of the great toxicity of colchicine in man. In one case of adenocarci- 

 noma of the bowel, the progressive increase of the mitotic index 

 could be followed by repeated biopsies. The control specimens had 

 an index of 2.6, which rose to 7.-^ Aac hours after colchicine and 

 reached 19.6 after 12 hours. This last biopsy demonstrated a con- 

 siderable increase of arrested mitoses. It is regrettable that, owing 

 partly to the too great danger of colchicine poisoning (cf. Chapter 7) , 

 no further research of this type has been conducted. Now that new 

 and less toxic colchicine derivatives are available^o (Chapter 17), a 

 more thorough study of the rate of growth of human neoplasms may 

 be possible. This could then be compared with data on normal tis- 

 sues obtained by the same method. 



Colchicine may yet be used on explanted human tissues, and it 

 is surprising that only iwo papers on tliat sul^ject can be recorded 

 up to now. In polycythemia vera, a disease in which the abnormal 

 number of red blood cells has often been considered closely related 



