Cell Division 



113 



— SH in dividing cells. S — S linkages, on the 

 other hand, are thought to play a role in the 

 formation of the protein gels of mitotic 

 organelles. Indeed, Brachet has found that 

 asters, spindle and the nuclear sap from 

 which it is formed are especially rich in 

 — SH after denaturation. Since — SH groups 

 are also essential to the functioning of many 

 enzymes (cf. Barron, '51), the effect of thiols 

 on mitosis may be quite diverse. 



As mentioned above, the original state of 

 affairs may be illustrated by the amoeba 

 that grows to a certain size and then divides. 

 Cells of metazoa no longer behave that way; 

 they are dependent on checks and balances 

 originating in the tissue, organ or organ- 

 ism as a whole. Single cells in tissue culture 

 are said to be imable to divide except under 

 special conditions (Likely et al., '52); usu- 

 ally there is a minimal number of cells 

 below which growth does not occur (Fischer, 

 '46). In the developing embryo, during re- 

 generation, in buds of asexually reproducing 

 animals this control of cellular proliferation 

 has been demonstrated many times. Cell 

 division in an organ stops when the proper 

 relative size is reached and only where con- 

 tinuous replacement is necessary, as in the 

 intestinal mucosa or in the skin, do we find 

 mitoses. If the balance is upset by removal 

 of tissues or by other injuries to the cells, 

 proliferation sets in again until the normal 

 functional balance is restored. 



What factors are responsible for the con- 

 trol of proliferation and what cavises renewed 

 mitotic activity? 



With the introduction of tissue culture 

 techniques it became possible to study the 

 factors responsible for initiation of mitosis 

 directly and under controlled conditions. The 

 mitosis-stimulating effect of embryo extracts 

 and adult tissue extracts was discovered and 

 the search was on for the nature and mode 

 of action of "growth factors." Much interest- 

 ing information has been collected in the 

 years since (see Fischer, '46), but it still 

 remains unknown how these extracts act 

 on the cells of the explant and how they 

 stimulate mitosis. The facts indicate that 

 substances released by injured cells and tis- 

 sue extracts contain a whole spectrum of 

 factors, substrates, coenzymes, bviilding 

 blocks and possibly self-reproducing enzyme 

 systems (cytoplasmic particvilates; Shaver, 

 '53). It remains for fiiture work to separate 

 these factors and study their specific mode 

 of action on the cell. 



The mitosis-stimulating effect of injury 

 substances and tissue extracts has been stud- 



ied not only in explants but also in the in- 

 tact animal. Tissue extracts accelerate the 

 healing of wounds (Auerbach and Doljanski, 

 '45). Tumor extracts increase the growth of 

 tumors (Annau, Manginelli and Roth, '51) 

 and other tissvies. Even more interesting is 

 the organ-specific action of tissue extracts. 

 Injury of a certain tissue was shown to re- 

 lease factors that stimulate mitosis in homol- 

 ogous tissues, but not in others. These fac- 

 tors are carried in the blood stream (Teir, 

 '52). Similar results were obtained by Weiss 

 ('52) in embryos. Homologous tissue ex- 

 tracts delay differentiation and stimulate cell 

 proliferation. These experiments so far sup- 

 port Weiss' hypothesis of self-regulation of 

 organ growth by diff visible products. Accord- 

 ing to Weiss a cell produces "templates" in- 

 volved in the production of new specific 

 cytoplasm and diffusible units that move into 

 the humoral pool. If these reach a certain 

 concentration further proliferation of the 

 particular cells is inhibited, since the dif- 

 fusible units combine with and inactivate 

 the "templates." By injecting tissue extracts 

 the concentration of the homologous humoral 

 units is reduced and this leads to renewed 

 proliferation in the particular tissue. 



Superimposed on the self-regulation of 

 organs is the activity of hormones. Bullough 

 ('52) has recently reviewed the effect of hor- 

 mones on mitotic activity in vertebrates. Both 

 androgens and estrogens stimulate mitosis, 

 except in nerve cells and striated muscle. 

 Adrenal hormones, on the other hand, de- 

 press mitotic activity. This hormonal con- 

 trol of mitosis apparently operates by in- 

 fluencing the availability of carbohydrate to 

 the cell. 



Another kind of tissue interaction was 

 discovered by Carrel ('22). Fibroblasts can 

 grow in serum alone in the presence of 

 leukocvtes. He called the substance liberated 

 by leukocytes "trephones." The role of such 

 trephocytes has been investigated recently, es- 

 pecially by Liebman ('47). The nature of 

 trephones is unknown; they may be nutrients, 

 vitamins or enzymes. Bactei-ia in tissue cul- 

 ture or even in vivo may act as trephocytes 

 (Lasfargues and Delaunay, '49). Wooley 

 ('53) has shown that tumors may act simi- 

 larly. Mouse embryos deficient in B12 could 

 ffrow if the mother carried certain tumors. 

 These tumors synthesized B]2 which then be- 

 came available to the embryonic tissues, en- 

 abling them to grow. In this connection it is 

 of interest that certain tumors can grow in 

 serum alone, while normal tissues need spe- 

 cial growth factors in addition. It appears 



