ANTIMITOTIC ACTIONS 523 



potency 30- to 40-fold and induces a specificity not seen in the former 

 compound. It is unfortunate that, as in most work of this type, there are 

 no data available on nonquinonoid polycyclic compounds, although it is 

 known certainly that phenanthrene and benzanthracene exert fairly po- 

 tent antimitotic actions on other cells. 



Lehmann divided antimitotics into two general categories on the basis 

 of their cytoplasmic and nuclear actions: 



(I) Inhibitory antimitotics: inhibit cytoplasmic movement, and hence 

 cleavage, without significantly affecting the nucleus (e. g., p-benzoquinone 

 and 1,4-naphthoquinone). 



(II) Destructive antimitotics: interfere with and destroy the nuclear ap- 

 paratus (karyolytic action), without affecting cytoplasmic movements, so 

 that cells may divide with defective nuclei (e. g., colchicine, diethylstil- 

 bestrol, and 9,10-phenanthraquinone). 



Such differences in action introduce further complexities and make it doubt- 

 ful that substances appearing to exert similar effects in Fig. 5-7 really act 

 by identical mechanisms. It may be mentioned that other benzoquinones 

 studied (toluquinone, methoxytoluquinone, and chloranil) all seem to act 

 like p-benzoquinone in having little effect on the nucleus. The substituted 

 naphthoquinones (e. g. menadione) also probably behave similarly to the 

 parent compound, whereas 1,2-naphthoquinone only cytolyzes and is not 

 directly antimitotic. If one might hazard a guess, the polycyclic structure 

 may be effective in disturbing nuclear function and modifying embryonic 

 development, whereas an active quinone tends to cause damage to the 

 plasma membrane, leading to cytolysis; since cleavage can be stopped by 

 a number of mechanisms, possibly either structure interferes. It seems very 

 unlikely that a compound could exert a specific effect on cytoplasmic move- 

 ments without simultaneously depressing certain other cell functions and 

 producing damage, the degree depending on the duration of exposure. The 

 nature of the nuclear action is unknown, but it was postulated that the 

 blocking of cleavage by ^^-benzoquinone is due to the alteration of cytoplas- 

 mic structure from a sol to a gel state, a reaction involving structural pro- 

 teins rather than enzymes. However, in view of the recent work demonstrat- 

 ing a relationship between the sol-gel state, metabolism, and ATP, an 

 effect on enzymes cannot be excluded. 



It was shown that j9-benzoquinone, when present in low concentration, 

 is taken up rapidly and completely by eggs, whereas colchicine is taken up 

 slowly and only in unmeasurable quantities. Using small volumes of fluid, 

 Lehmann calculated the amount of quinone taken up by the eggs (see 

 accompanying tabulation). He termed this a "biological titration" of the 

 quinone, since one must specify the absolute amounts required to produce 

 specified effects. Nevertheless, it must be remembered that not necessarily 



