196 KARL C. LARK 



the DNA rt'plication cycle it'^elf or sonic other ]);ir;iinctci-c()iit rolling 

 replication rate) before increasing the DNA synthetic rate. However, a 

 phasing of synthesis as observed with libonucleotides would intlicate that 

 the DNA cycle of individual cells may be composed of at least two 

 components, which differ markedly in their response to nutritional 

 changes in the medium. Such an explanation would be consistent with the 

 observed effect of temperature on such cells. 



The stimulation of DNA synthesis as a result of wounding (see Sec- 

 tion V,B) is characterized by a stimulation of cells often far removed 

 from the area of trauma. This suggests the ingestion by these cells of 

 some compound or comi)ounds capable of stimulating DNA synthesis. 

 These may be cellular breakdown products. On the other hand, ingestion 

 of foreign substances may give rise to a similar stimulation. Dutton 

 et al. (1962) have studied the stimulation of DNA synthesis which 

 occurs upon addition of a specific antigen to spleen cells taken from an 

 innnunizcd animal. It would appear probable that the results of further 

 detailed study of this system could be applied with profit to the study of 

 regenerating systems, especially with reference to the ability of humoral 

 factors to stimulate specific tissues or organs. 



Deoxynucleosides and tides have been observ^ed to increase the rate 

 of division and mitosis of cells (Karpfel et al., 1959; Firshein and Braun, 

 1960; Butros, 1959; Gruelich et al, 1961) as well as of DNA synthesis 

 (Firshein, 1961). A study of the effect of deoxynucleosides on the timing 

 of DNA synthesis in synchronized bacteria (Lark, 1960) demonstrated 

 that addition of low concentrations of the four deoxyribosides (deoxy- 

 cytidine, thymidine, deoxyguanosine, and deoxyadenosine) would destroy 

 periodic DNA synthesis. This effect only occurred if these compounds 

 were present intracellularly during a period of DNA synthesis (ap- 

 proximately 30% of the division cycle). Deoxyribosides are normally 

 not found within such cells (see Section II), which have been shown to 

 contain deoxynucloetides only. The observed effects were interpreted to 

 indicate: (a) that during the period of DNA synthesis the control of the 

 synthetic process could be affected by these substances, presumably as 

 a result of their competition with nucleotides engaged in base-pairing 

 with primer (this might extend the period of DNA synthesis) ; and (b) 

 that the time of initiation of a period of DNA synthesis was related, in 

 some manner, to the time at which a previous cycle had been completed. 

 It was assumed that a lack of absolute synchrony would lead to a dif- 

 ferent response by individual cells to the competitive effects of deoxy- 

 ribosides tending to further randomize the population and destroy 

 synchrony. 



