IV. CELLULAR CONTROL OF DNA BIOSYNTHESIS 191 



synthesis. E. coli is known to synthesize DNA throughout most of its 

 cell cycle (see Introductionj. However, the same type of complex is 

 found at all times in synchronous cultures of A. jaecalh, which synthe- 

 size DNA discontinuously (Billcn and Lark, unpublished data). 



B. VARIATION IN THE DNA CYCLE 



Whereas rapidly dividing cells in tissue culture often exhibit a pre- 

 cisely defined cell cycle, the same is not necessarily true for cells growing 

 in the animal. Mendelsohn et al. (1960) have shown that transplanted 

 tumor tissue shows a large variation in the length of the period preceding 

 DNA synthesis (GJ, whereas both .S and Go remain rather constant 

 over the cell population. Studies on the intestinal epithelium and the ear 

 epidermis of the mouse (Quastler and Sherman, 1959; Quastler, 1960; 

 Sherman et al., 1961) have shown a similar variation in G'l, as opposed 

 to S or Go. Moreover, different cell types from the same animal showed 

 differences in the average length of their Gi periods. Differences were 

 also observed in S and Go, but these were much less striking. In addition, 

 it was possible to show that the decision as to whether an intestinal 

 epithelial cell should cease dividing and differentiate (move into the 

 villi) or to continue proliferation, was taken during the early portion of 

 the cell cycle before DNA was synthesized. On the other hand, cells of 

 the epidermal layer of the ear often ceased division in the Ga (Gelfant, 

 1960) as well as the Gi (Gelfant, 1961) stages. However, the low tem- 

 perature at which these cells are growing may account for a mitotic 

 block arresting cells in G2. 



Upon injury, cells may move out of both Gi and G2 to commence 

 DNA synthesis and/or division. This has been demonstrated with cells 

 of the epidermal layer of the mouse ear and a similar situation may 

 exist in tissue of the eye (Harding and Srinivason, 1961). It is, of course, 

 known to exist in liver as evidenced by the events involved in regenera- 

 tion (Barnum et al., 1957). Injury would appear in these cases to pro- 

 voke a humoral response capable of initiating DNA synthesis and hence 

 cell proliferation. Thus, partial hepatectomy of one animal will result in 

 liver proliferation in another animal which is placed in parabiosis with 

 it (Bucher et al, 1951). 



It is interesting to note that during liver regeneration a good deal of 

 the variability between the DNA cycles of individual animals (as evi- 

 denced by increasing asynchrony of DNA synthesis) may be reduced by 

 the use of inbred strains of the same age which have been partially 

 hepatectomizcd at the same time. This would indicate that the inherent 

 rate of progression through Gi may be related, in some way, to a diurnal 



