530 L. G. LAJTHA 



As RNA synthesis occurs throughout the cell cycle, and indeed, is not 

 inhibited by inhibition of mitosis, no depression of RNA synthesis (or pro- 

 tein synthesis) would be expected either. 



It is clear from the examples above, that inhibition of mitosis alone may 

 cause a depression of "DNA synthesis" as measured by the specific activity 

 of DNA. It is also clear that a depression of specific activity of DNA does 

 not necessarily mean that the process of DNA synthesis is in any way af- 

 fected in any cell remaining alive or not being held up in mitosis after ir- 

 radiation. Although work at the cellular level (autoradiography of single 

 cells) would avoid most of the above mentioned pitfalls, unfortunately a 

 great bulk of early work involved the use of DNA specific activity as an 

 index of DNA synthesis after irradiation; consequently their results need 

 reinterpretation in light of more recent experiments. 



However, the above cited changes, shifts, and delays need a certain time 

 to develop and it has been suggested that if experiments are limited to an 

 observational period not exceeding 2 hours after irradiation, there will 

 not be sufficient time for significant population effects. 4 In short term ex- 

 periments a depression of DNA specific activity may well measure depres- 

 sion of the biochemical process of DNA synthesis. It should be noted never- 

 theless, that while a 2-hour period may be too short in a large mammal to 

 register population effects, it may be a borderline time in a small rodent, 

 and too long a time for certain organisms with fast cell cycles. 



4. Changes Observed within One Interphase 



The scheme of events in respect to DNA synthesis in an average inter- 

 phase of an average cell may be illustrated in Fig. 1 . 



It should be noted that the times spent in each period may vary greatly 

 with different cell types. The length of the S period may vary from 6 hours 

 (Vicia faba) 6 to 10-12 hours (human bone marrow cells in vitro, 7 the length 

 of the Gi period from being undetectable (Ehrlich ascites cells of the mouse) 8 

 to over 20 hours (human bone marrow cells in vitro), 7 and the G 2 period from 

 less than 2 hours (mouse intestinal epithelium) 9 to about 71^ hours (Ehrlich 

 ascites cells of the mouse). 8 



If short term experiments are being performed, i.e. if the label is adminis- 

 tered immediately after irradiation and the sample is obtained within 1-2 

 hours of labeling, then almost all cells which will show labeling will have 

 been in their S period at the time of irradiation. Such experiments can meas- 

 ure the effect of radiation on the DNA synthetic period (S effect). In cells 

 which have a suitably long Gi period, the label may be administered 10-12 

 hours after irradiation, by which time all those cells which at the time of 



8 S. Hornsey and A. Howard, Ann. N. Y. Acad. Sci. 63, 915 (1956). 



9 H. Quastler and F. G. Sherman, Exptl. Cell Research 17, 420 (1959). 



