Influence of Radiation on DNA Metabolism 201 



manner depends on the rate at which they reach mitosis. The 

 extent of tissue damage is greater at higher doses, dose rates, 

 and ion density of the radiation. 



(b) In a manner not known to be associated with physio- 

 logical or morphological changes in the chromosomes, and 

 not due to loss of genetic material. Cells may die upon 

 attempting division (Laznitski, 1943a; Oakberg, 1955); in this 

 case, the rate of cell death again depends on the rate at which 

 cells reach mitosis, as in (a). They may, on the other hand, die 

 during the interphase in which they were irradiated, independ- 

 ently of any recovery of mitotic activity. The sensitivity of 

 cells to this kind of interphase death is enormously varied. 

 Lymphocytes in the lymph nodes are rapidly destroyed by 

 100 r (Trowell, 1952): in mouse ascites tumour there is no 

 evidence of cell death after 1250 r, at least until mitosis 

 reappears (Klein and Forssberg, 1954); chick fibroblasts in 

 culture exhibit interphase death at 2,500 r (Laznitski, 19436); 

 and some differentiated tissues having no measurable mitotic 

 activity are histologically unaffected by even higher doses 

 (Bloom, 1948a). In this respect, the lymphocyte appears to be 

 very exceptional, and it seems reasonable to regard interphase 

 death, of a kind unrelated to mitosis, as very unlikely in most 

 tissues except after doses of well over 1,000 r. 



Results of Changes in Cell Populations 



After moderate doses of radiation, i.e. less than about 

 1,000 r, the shifts described would be expected to affect the 

 amount of DNA being synthesized in a tissue as follows : 



(1) The time at which the normal supply of cells entering 

 synthesis is reduced will depend upon the time in the cell cycle 

 at which DNA is normally synthesized. If synthesis begins 

 immediately after telophase, irradiation will have an early 

 effect in reducing the number of synthesizing cells. If there is 

 a time lag between telophase and synthesis, the effect of 

 irradiation will be deferred until this time has elapsed. Fig. 1 

 shows the time of uptake of labelled precursors into DNA, and 

 the estimated lengths of other periods, in the mitotic cycles 



