40. RADIATION AND NUCLEIC ACID METABOLISM 545 



To conclude: there is some evidence which may explain, at least in general 

 terms, the mechanism of radiation effect on DNA synthesis within one 

 interphase (mitotic inhibition excluded). 



According to this evidence the following scheme may be put forward: 

 intranuclear triphosphorylation — a very radiosensitive function — is respon- 

 sible for the normal rate of processes during the presynthetic period (Gi 

 period), and also for the normal rate of DNA synthesis during the synthetic 

 period (S period). If this function is destroyed, both the Gi "progress" and 

 the rate of DNA synthesis will be depressed. In most cells so far investigated 

 it is responsible for about 50% of the processes involved. 



It should be emphasized that not all cells may behave in a similar fashion. 

 In particular, long term tissue culture cells capable of sustained growth in 

 semisynthetic or fully synthetic media may be rather special exceptions; 

 their Gi "progress" may not depend on this nuclear process, as indicated 

 by observations on HeLa S 3 cells, 85 although even in these cells some of the 

 findings could be explained on the basis of a sensitive Si factor. In cells 

 which do not depend greatly on this radiosensitive function, DNA synthesis 

 may not be delayed greatly, as indeed is indicated by studies with NCTC 

 strain L fibroblast. 86 The dose of radiation employed in both these experi- 

 ments was 500 r. and 800 r., respectively — doses not likely to affect the S2 

 factor (? DNA matrix) significantly. 



There may also be some cell types or experimental conditions in which 

 there is no observable Si effect. This may be due to intrinsic absence of the 

 Si factor in the cells, or loss of it under the particular experimental condi- 

 tions. Ehrlich ascites tumor cells appear to be an example for the latter. 58 



V. General Conclusion 



As was pointed out in the introduction, the study of radiation effects on 

 nucleic acid metabolism was, to a great extent, initiated in the hope that 

 radiation induced disturbances in nucleic acid metabolism might give the 

 explanation to the primary lethal actions of radiations in the cell. 



It has been indicated from the foregoing that is is not the case. First, most 

 (although not all) primary lethal actions of radiations are due to inhibition 

 of mitosis, chromosome damage, or gene mutations. These can be produced 

 by smaller doses of radiation than would measurably affect the process of 

 DNA synthesis. Second, radiation induced changes in DNA synthesis are 

 themselves, to a great extent, results of more sensitive underlying biochemi- 

 cal processes, and, contrary to early beliefs, the process of DNA synthesis 

 itself is rather radioresistant. 



Nevertheless, radiation has proved to be an extremely useful tool for the 



85 R. B. Painter and J. S. Robertson, Radiation Research, in press (1959). 



86 M. Dickson, J. Paul, and J. N. Davidson, Biochem. J. 70(4), 18P (1958). 



