THE MITOTIC CYCLE 



embryonic cells. The immature leucocytes possess a certain plasticity 

 and pluripotentiality and are capable of producing many types of 

 protein (serum globulins, including specific antibodies). Ludford^^ is 

 among those who link the activity of the leucocytes in vitro with their 

 ability to cause breakdown of proteins for cell nutrition. It is necessary, 

 therefore, to examine the evidence concerning the mitosis-stimulating 

 effects of partial and complete breakdown products of proteins. 



Protein breakdown products 



Embryo extracts have been shown to have proteolytic activity 

 (Guillery;'^ Albert and Hecht;^^ Santesson^"). It has been claimed 

 that protein breakdown products — e.g., proteoses — are capable of 

 contributing to very extensive increase in area of fibroblast colonies, 

 by stimulating migration (Willmer and Kendal^i), ^ut that they do 

 not promote cell multiplication in the absence of the thermolabile 

 materials of embryo extract (Baker^s). In the presence of embryo 

 extract, however, various fractions from Witte peptone (Baker and 

 Carrel^^) or from partial digestion of purified proteins (Carrel and 

 Baker^* ^^) cause exceptionally extensive and vigorous growth of 

 fibroblast colonies. Fischer^^ found that peptides from chicken plasma, 

 in contrast to those from heterologous proteins, promoted the growth 

 of normal chick fibroblasts in the presence of dialysed plasma and 

 dialysed embryo extract. Proteolytic enzymes, either on the cell surface 

 or in the plasma, are believed by Fischer^' to attack, after activation, 

 e,g,^ by glutathione, proteins which are fixed and partially denatured 

 on the cell surface. Hueper and Russell^^ found that ultraviolet 

 irradiation of chick embryo extract did not destroy its growth- 

 promoting power, nor did the addition of glutathione or cysteine en- 

 hance the activity of the irradiated extracts. Verne and Verne- 

 SouBiRAN^^ on the other hand inactivated embryo extract by heat 

 ( 1 00°) and found that it could be to some extent reactivated by gluta- 

 thione. Stored embryo extract, which also lost its growth-promoting 

 power, could not be reactivated in this way. Hueper et alii^^ could find 

 no evidence that the — SH group per se has a selective mitosis-stimulat- 

 ing effect. However, a strong, if not necessarily casual, relationship 

 between the presence of reduced sulphydryl groups and the activities 

 of cell division has been firmly established by the work of 

 Hammett,^! 92 93 VoEGTLiN and Chalkley,^* Rapkine^s and others. 

 The fact that the — SH group is an activator of many enzymes, includ- 

 ing proteolytic enzymes (Hammett and Lavine^^) leaves it an open 

 question whether the influence is indirect and nutritional or rather, as 

 Hammett ^1 stated earlier, that sulphydryl exerts its effect 'through its 

 specific stimulation of cell division and not through a forwarding 

 influence on assimilative or cell size growth'. An optimal concentration 



172 



