Influence of Radiation on DNA Metabolism 203 



incompatible with the pubhshed results of irradiation experi- 

 ments in this material (Klein and Forssberg, 1954; Forssberg 

 and Klein, 1954), and are in agreement with some recent work 

 of Kelly (1955). 



(2) The degree to which DNA synthesis is affected will be 

 determined largely by the length of S (see Fig. 1) in relation to 

 the time length of the premitotic block. Thus the synthesis of 

 DNA in a tissue will be reduced to zero if the mitotic block 

 (plus Gj if it exists) is longer than S. In the Ehrlich ascites 

 tumour, a dose of 400 r stops mitosis for 9 to 12 hours. Since 

 S is about 12 hours, we would not expect to observe a period 

 when there was no synthesis, and after 12 hours there would 

 be a larger than normal number of synthesizing cells, as has in 

 fact been observed (Hornsey and Howard, unpublished). 



(3) The recovery of DNA synthesis in a tissue will depend 

 upon the factors discussed under (2), i.e. the degree of depres- 

 sion, and also on the rate of cell death, the degree of tissue 

 disturbance caused by it, and any other effect which the 

 presence of dead or dying cells may have on the metabolism 

 of the survivors. These last two points we know little about. 

 The effect on specific activity will further depend on the rate 

 at which dead cells are removed from the population, either 

 by phagocytosis, migration, or some concomitant of differen- 

 tiation. The rate of return of the tissue to normal will be 

 influenced by its normal rate of cell replacement: thus in 

 the small intestine, where epithelial cells normally have a life- 

 time of approximately 2 days (Leblond, Stevens and Bogoroch, 

 1948; Knowlton and Widner, 1950), the regeneration of the 

 epithelium is very rapid (Bloom, 1948Z?) and DNA synthesis 

 has recovered by 1 day (Kelly et a/., 1955). The mitotic index 

 in the rat intestinal mucosa recovers by 3 days after 1,000 r 

 (Webber, Craig and Friedman, 1951). 



Conclusions 



In view of these considerations, it is plain that a purely 

 biochemical analysis of a growing tissue containing cells at all 

 mitotic stages cannot tell us whether the inhibition of DNA 



