EFFECTS ON MITOSIS, GROWTH, DIFFERENTIATION 253 



EFFECTS ON MITOSIS, GROWTH, AND DIFFERENTIATION 



Interference witli proliferation and growth of cells by inhibitors is often 

 attributable to the inhibition of the syntheses of certain necessary cell 

 components. lodoacetate is able to depress the formation of most of the 

 basic macromolecules and substances involved in the cell structure; these 

 effects have been discussed in the sections on metabolism of proteins (page 

 147), polysaccharides (page 133), photosynthesis (page 157), lipids (page 

 144), and porphyrins (page 155). We shall only add here a few observations 

 which seem pertinent to the problems of growth. In most cases the inhibi- 

 tion of the syntheses of complex molecules is nonspecific in the sense that 

 it is due simply to a reduction in the energy available for assemblage, and 

 very little is known about the possibilities of specific interference in the 

 more terminal pathways. 



lodoacetate depresses protein synthesis quite potently but the exact lo- 

 cation of the site, or sites, of attack has not been determined. In addition 

 to the investigations previously presented, we may note that the following 

 are markedly inhibited: the incorporation of acetate-1-C^^ into tumor pro- 

 teins (van Vals and Emmelot, 1957), the formation of the adaptive enzyme 

 for the oxidation of benzoate in Mycobacterium lacticola (Fitzgerald etal., 

 1949), the biosynthesis of proteinase in Streptococcus liquefaciens (Rabin and 

 Zimmerman, 1956), and the incorporation of a variety of amines into the 

 proteins of guinea pig liver (Clarke et al., 1959). The studies of Ogata and 

 his associates (1956, 1958) are particularly interesting. They followed the 

 incorporation of glycine-C^^ into the antibody to ovalbumin and various 

 other proteins in rabbit lymph nodes. The formation of antibody, nucleo- 

 protein, mitochondrial protein, and microsomal protein is reduced 70-85% 

 by 2 mM lodoacetate in cell suspensions, and comparable inhibitions are 

 produced in homogenates. The incorporation of glycine-C^^ into the proteins 

 of slices of regenerating liver is more strongly inhibited, essentially a com- 

 plete block being established by 1 mM lodoacetate. There is also evidence 

 that lodoacetate can interfere with the biosynthesis of purines, as in ascites 

 tumor cells (Henderson and LePage, 1959), or of nucleic acids,- as in brain 

 slices (Findlay et al., 1953) and in spleen, intestine, and thymus (Quinti- 

 liani et al., 1961). Glycogen synthesis is almost invariably depressed by 

 lodoacetate, but other polysaccharides may be included, for example that 

 of pneumococcal capsules, the formation of which is strongly inhibited by 

 0.1 mM lodoacetate (Bernheimer, 1953). A full realization of such bio- 

 synthetic inhibitions must form one basis for the interpretation of the studies 

 on growth and differentiation. 



Mitosis 



The effects on mitosis and cleavage associated with plant growth, em- 

 bryogenesis, tumors, and proliferation of microorganisms will be taken up 



