IV. CELLULAR CONTROL OF DXA BIOSYNTHESLS 195 



result is similar to the effect of cold shock on such cells (Smith et al., 

 1959). 



These results serve to (listinf2;uish two classes of cells in the randomly 

 dividing population. Presumably these differ with respect to when in 

 their DNA synthetic cycle they have been subjected to the inhil)itoiy 

 agent. 



This has been further clarified by Taylor et al. (1962), who have 

 demonstrated that thymidine deprivation will only block mitosis if it 

 occurs early in *S. On the other hand, cells subjected to FUDR late in 

 S proceed into mitosis with a concomitant fragmentation of the chromo- 

 some. Removal of the thymidine block and addition of thymidine as late 

 as 1 hour before anaphase will prevent fragmentation. This may indicate 

 that incorporation of thymidine into specific sites in the nuclear material 

 may be necessary even during Go if the integrity of the chromosome is to 

 be maintained. This has been substantiated by Hsu and Somers (1962). 

 They demonstrated that the number of chromosome breaks increased in 

 proportion to the length of time prior to mitosis (that is, in Go or 5) 

 that cells were subjected to low concentrations of FUDR. The number 

 of breaks increased continuously showing no sudden rise in number 

 which would reciprocally represent a transition from »S to G-.. 



Under certain conditions alteration of the nutritional environment 

 may alter the DXA cycle without l)locking cell growth or division. Only 

 a few such experiments will be discussed. 



Bacteria {E. coli) when grown exponentially under conditions of 

 balanced growth appear to synthesize DNA throughout the majority of 

 their division cycle (Schaechter et al, 1959). However, when ribosides are 

 added to the medium DXA synthesis becomes cyclic, occurring in steps 

 separated by periods in which almost no synthesis takes place (Lark 

 and Lark, 1962). No phasing was observed in cell division, although the 

 over-all growth rate was increased. This result is related to the findings 

 of Kjeldgaard et al., (1958», who observed a delay before the rate of 

 DNA synthesis was increased as a result of shifting bacteria to a 

 medium in which growth occurred at a faster rate. No phasing of DNA 

 was reported at this time, although the data indicate that some may in 

 fact have occurred. In this case, phasing of nuclear division was reported. 

 Subsequent studies (Maal0e, 1961) have shown that during the transition 

 period in which the synthetic rate is eventually increased, the cell popu- 

 lation becomes heterogeneous, some cells commencing to synthesize 

 DNA at a more rajiid rate than others. These results indicate that fol- 

 lowing a "shift up" into a richer medium two classes of cells may be 

 eventually distinguished. Maal0e (1961) has interpreted this to indicate 

 that cells must complete a given pliysiological pattern of events (either 



