THE MITOTIC CYCLE 



gelation and cleavage in marine eggs are heparin,* a bacterial poly- 

 saccharide (Heilbrunn and Wilson^^^) extracts of tissues such as the 

 ovary of Asterias (Heilbrunn et aliP^^) and the dye Janus Green B 

 (Allen^^') which is also effective as a blood anticoagulant. These 

 observations are relevant to Heilbrunn's theory that 'protoplasmic 

 clotting' is involved in cell division (p 140). 



The specificity of the action of colchicine on the spindle is illustrated 

 by comparison with substances such as the narcotics which inhibit cells 

 in metaphase at concentrations not much less than those at which their 

 other effects are exerted. Thus colchicine is without influence on cyclosis 

 in Tradescantia staminal hair cells (Nebel and Ruttle;238 Derman^^®), 

 while this activity in Elodea leaves is depressed by chloroform at 

 0-025 ^* (Medes and McClendon^^^), a concentration little more than 

 twice that needed to inhibit the spindle in Allium root-tips (Oster- 

 GREN^^*') with this narcotic. Again, photosynthesis in Elodea ceases 

 when benzene at mitotic-inhibiting concentrations is added. Even 

 I per cent colchicine has little effect on photosynthesis (Gavaudan 

 and Brebion^^i). 



OsTERGREN^^'^ has shown that in a number of organic compounds, 

 water solubility is inversely proportional to their effectiveness as spindle 

 inhibitors, measured by the greatest dilution at which they act on divid- 

 ing cells in Allium root-tips. Such relationships have been expressed by 

 Ferguson262 jj^ physico-chemical terms. Where substances of low 

 water-solubility exert toxic effects, the ratio between their threshold 

 toxic concentrations and their solubility is known as the 'thermo- 

 dynamic activity' of the compound and varies between ci — i-o for 

 'unreactive substances of the typical narcotic type', which act in a 

 purely physical manner, while chemical reactions with cell constituents 

 probably occur where the value of the activity coefficient is very low. 

 Gavaudan et alii^^^ have calculated the 'thermodynamic activities' of a 

 number of mitotic inhibitors; the lowest values are those of colchicine 

 and hexa-nitrodiphenylamine. 



The action of narcotics on the mitotic spindle is a comparatively 

 recent addition to the list of the inhibitory effects of these substances, 

 and can best be considered in relation to their general subject action 

 within the cell, a subject recently reviewed by McElroy^^* and by 

 Danielli.2^^ The most significant contribution to this field in 

 recent years has been the discovery that high hydrostatic pressure is 

 able to counteract the effect of some narcotics on bacterial luminescence 

 (Johnson et alii^^^). This has led to the view that these substances cause 

 a reversible denaturation of enzymic proteins, and that pressure in- 

 fluences this equilibrium in favour of the native form. This theory 



* Heparin has been found to prevent the agglutination of cytoplasmic particles isolated 

 from lymphocytes (Hoster et alii-^''^). 



