204 Alma Howard 



synthesis is due only to changes in the cell population, or 

 whether we may infer that irradiation is also having a primary 

 biochemical effect. For this information we must look to 

 experiments of the following kinds : 



(1) Biochemical analysis of growing tissues supplemented 

 by studies on mitotic delay and cell death. The few published 

 studies on inaterial for which such information, however 

 fragmentary, is at hand, are compatible with the view that 

 inhibition of DNA synthesis is a result of radiation-induced 

 changes in the mitotic cycle and in the cell population. On 

 the other hand, it must be recognized that there are in the 

 literature some experimental results which can be explained 

 as due entirely to cell population changes only by assuming 

 characteristics of the normal mitotic cycle that may appear 

 unlikely. Thus Hevesy (1945) observed that in Jensen rat 

 sarcoma, a dose between 335 and 1,500 r reduced ^^P uptake 

 into DNA to less than half of normal within one hour of irradi- 

 ation. Unless this is an interphase effect, one must suppose 

 that synthesis follows telophase directly and occupies less 

 than 2 hours. 



(2) Observations on individual cells. This has been done 

 with autoradiographs in experiments discussed previously. 

 In the case of bean roots, Howard and Pelc (1953) concluded 

 that the most probable length of G^ was 12 hours, and there- 

 fore that DNA synthesis was inhibited in cells irradiated 

 earlier in the ^ame interphase, i.e. 6-12 hours before the 

 beginning of synthesis. Since, however, the length of G^ can- 

 not be rigorously fixed from the information available, it is 

 not excluded that the sensitive period for inhibition of DNA 

 synthesis may coincide with that for delay in mitosis. The 

 results of irradiating the ascites tumour (Hornsey and 

 Howard, unpublished) are, as already stated, those to be 

 expected from mitotic delay. Lajtha, Oliver and Ellis (1954) 

 observed an immediate effect on synthesis of DNA in human 

 bone marrow cells in culture. The dose used was, however, so 

 large (5,000 r) that interphase death is to be suspected. No 

 cell was observed to enter mitosis after this dose. 



