ANTIMITOTIC ACTIONS 



521 



effect has reached its peak that somewhat higher concentrations begin to 

 block cleavage. It may also be noted that cytolysis begins to occur at the 

 same concentration as mitotic blockade, so that p-benzoquinone is not a 

 specific antimitotic at any concentration. However, it is possible by treat- 

 ment of the eggs for short periods to induce mitotic blockade without 

 subsequent cytolysis. The effects of several quinones are shown in Fig. 5-7 

 and their potencies and types of action are compared with colchicine and 



0.0004 0.0008 



p-BENZOOUINONE(tnM) 



0.0012 



Fig. 5-6. Effects of p-Q on the development of Tubifex 



eggs. (A) Normal embryos; (B) abnormal blastulas; 



(C) cytolyzed cells; (D) mitotically blocked cells. (From 



Lehmann and Hadorn, 1946.) 



diethylstilbestrol. It is interesting that ?)-benzoquinone is at least 100 times 

 more potent than colchicine and 15 times more potent than diethylstil- 

 bestrol, but does not possess the specificity of action evident with these 

 drugs, neither of which seems to induce cytolysis even at high concentra- 

 tions. This implies that the cytolysis might be characteristic of the action 

 of quinones, and it is observed with other quinones (except for 9,10-anthra- 

 quinone, which is not antimitotic, or 5,6-benzanthraquinone, where solu- 

 bility limits the testing at higher concentrations). The lack of obvious cor- 

 relation between structure and either potency or type of action is remarka- 

 ble. It may be questioned as to how much of the effect is due to the quinone 

 groups and how much to the polycyclic ring systems, especially as polycyclic 

 aromatic compounds are capable of exerting potent effects on cleavage and 

 development. However, there is certainly no general increase in potency 

 with increase in the number of rings, p-benzoquinone being at least as po- 



