Mechanism of Colchlclne-Mitosis 



419 



amount of the synergist is always far greater, on a molar Ixisis, than 

 that of colchicine. For instance, while 5.5 mitoses per hundred were 

 found after 0.01 mg/ml of colchicine, the addition of 5 mg/ml of 

 Inilbocapnin increased this figure to 23.8. Forty times this dose of 

 bulbocajinin had no action on control cultures. With phlorizin the 

 results are very striking also. 



More than 8 times more mitoses are arrested when a solution of 

 phlorizin, which has no antimitotic action, is added to a concentration 

 of colchicine, which is only weakly antimitotic. Ihis is truly a syner- 

 gistic eflect. "' Its study may most probably increase oiu- knowledge of 

 the physiological action of colchicine, and further work along similar 

 lines with different types of cells is to be expected. 



Another interesting colchicine synergist has been reported by P. 

 Rondini and A. Necco (Tumori, 39:161-63, 1953). Italcliitie, an 

 acridine derivative, is itself a mitotic poison, affecting spindle and 

 chromosomes. Small doses, which do not affect mitosis, increase 

 markedly the action of colchicine on chick fibroblasts cultivated /// 

 xntro. Ihe principal results are apparent from Table 17.4. 



ly.^-^: The role of adenosme-lriphosphoric acid (ATP). That 

 the spindle functions, partly at least, as a fibrous contractile structure 

 has l>een aliirmed repeatedly. The contraction which takes place has 



TABLE 17.4 

 Synergic Action of Italchine and Colchicine on Tissue Cuitures of 



Chick Fibroblasts 

 (Mitoses counted after 48 hours' incubation with the drugs) 

 (After Rondoni and Necco) 



also been compared to that of muscle. While biochemical data about 

 the nature of the spindle proteins are lacking entirely, it could be 

 imagined that colchicine acted on the contraction mechanism. Most 

 cytological data (cf. Chapter 2) point to an action on the fibers them- 

 selves, which can be observed to "dissolve" into a "pseudospindle" or 

 "hyaline globule" luuler the inlhience of the alkaloid. In muscular 



