THE MITOTIC CYCLE 



Chevremont and Frederic, ^'^^ though adequate for proteins such as 

 keratin, is sufficiently sensitive for this purpose. It is generally true 

 that free — SH groups are abundant in tissues in which cells are fre- 

 quently dividing; the evidence for this generalization is reviewed by 

 Brachet.2^° 



Other effects of sulphydryl reactants in dividing cells 



Metaphase is not the only stage in mitosis which can be blocked 

 by sulphydryl reactants. The effect of iodoacetate in preventing the 

 entry into mitosis of cells in tissue cultures has already been des- 

 cribed (p 1 85) ; iodoacetamide and chloracetophenone, when added 

 to a culture when anaphase has just begun within a cell, can arrest 

 the further movement of the chromosomes, and at the same time 

 prevent cleavage and the reconstruction of the daughter nuclei. 

 When anaphase and telophase are inhibited by chloracetophenone in 

 this way, bubbling at the surface of the cell begins some minutes after 

 the addition of the agent, and increases in violence to such an extent 

 that the whole cell may be fragmented into blebs, among which the 

 daughter chromosomes are found unchanged still in their early ana- 

 phase relationship (Plate XV (27) ). 



HuGHES^*'^ has suggested that this blockage of nuclear reconstruction 

 may be due to inhibition of nucleases of the type described by Mayer 

 and Greco^'^ and associated with cathepsin, which is a complex of 

 sulphydryl enzymes. This suggestion, however, leaves unexplained the 

 fact that the formation of the chromosomes in prophase is compara- 

 tively insensitive to sulphydryl reactants in the fibroblastic cell, 

 although mitosis can readily be inhibited by such agents at several 

 other points. Inhibition in prophase can result if the action on the cell 

 is sufficiently drastic to arrest cytoplasmic movement, which also ceases 

 in intermitotic cells after prolonged treatment with high concentrations 

 of chloracetophenone. 



Chromosomal effects 



A number of substances affect the dividing cell primarily by attacking 

 the nucleoproteins and the chromosomes. These include the 'radio- 

 mimetic' agents of Dustin which cause dividing cells in the mouse to 

 degenerate. Among these are trypaflavine (Dustin (A. P.) 2'^) the effects, 

 of which on tissue cultures have been shown by Lettre and Lettre^'^* 

 to be counteracted by nucleic acids, both RNA and DNA, when added 

 to the medium of the culture. Not all the substances which affect the 

 nucleoproteins of the chromosomes induce the breaks and rearrange- 

 ments which persist in subsequent mitoses after the direct toxic effect 

 has disappeared (Loveless and Revell^^^). Chromosome breaks 

 which do not persist in subsequent cycles of mitosis are provoked by a 



196 



