266 Colchicine 



solution of colchicine, locally applied, decreased the number and the 

 volume of the induced tumors without disturbing the growth of the 

 plant itself. '^^ An extensive series of experiments was started shortly 

 after on seven species.^" By injecting colchicine in plants at the time 

 of infection by B. (urnefaciens, tumor growth was only prevented in 

 9 out of 61 plants. On the contrary, to arrest the growth of tumors 

 and to destroy them later were possible in most cases by several tech- 

 niques of application of the alkaloid. In Tagetes patula, these tumors, 

 after daily paintings with a 1 per cent colchicine solution, stop grow- 

 ing after 7 days and then progressively decrease and die. The princi- 

 pal microscopic effect is a great enlargement of the tumor cells, four 

 or five of the colchicinized ones occupying the area of 30 normal 

 ones. This enlargement is the most visible with rather concentrated 

 solutions of colchicine (up to 0.1 per cent) . The smallest cells are 

 64-ploid (1536 chromosomes), the larger 1014-ploid (24,500 chromo- 

 somes) . Some nuclei have irregular shapes and some cells are multi- 

 nucleated. Cellular death is a direct consequence of the extreme de- 

 gree of polyploidy which is reached, the giant cells becoming at some 

 stage quite unable to divide any further. There is no effect on the bac- 

 terial growth. !•' Similar results have been obtained in Pelargonium 

 and Riciiius.'- It was supposed that the death of the tumor was the 

 consequence of its isolation by a layer of cork."- 



Though animal cells, through failure of centromere division, can- 

 not usually go through repeated colchicine mitoses, it is thought- 

 provoking, however, to compare these effects with those of X-rays in 

 animal tumors. Cellular proliferation after X-ray therapy is also 

 stopped when cells become gigantic and highly polyploid through 

 repeated abnormal mitoses. 



10.7: Colchicine and X-rays Associated 



When the first work on colchicine and tumors was done in 1934, 

 ionizing radiations were supposed to have the most harmful effects on 

 mitotic chromosomes, and it was expected that accunudating such a 

 great number of divisions, as seen in sarcomas for instance, would 

 increase the radiosensitivity of the tumors (Fig. 10.1). Most recent 

 work, however, shows that the sensitive period of the mitotic cycle 

 is before prophase, and thus, accunudating metaphases could not be 

 expected to increase radiosensitivity since the rate of prophases is not 

 disturbed.^'' This is confirmed by most work on colchicine and tumors, 

 whether in animals or in plants. 



lo.-j-i: Animal tumors. X-rays were observed to be considerably 

 more efficient in killing in vitro tumor cells when these had been 

 previously treated by colchicine (Flexner-Jobling grafted carcinoma 

 of the rat) .^'^ Here the test used was the grafting of fragments of 



