Chapter 40 



The Effect of Radiations on Nucleic Acid Metabolism 



L. G. Lajtha 



Radiotherapy Department, The Churchill Hospital, 

 ' Headington, Oxford, England 



I . Introduct ion 527 



II. Factors Influencing Deoxyribonucleic Acid Specific Activity 528 



1 . Population Changes 528 



2. Population Shifts 529 



3. Cell Cycle Changes Due to Mitotic Delay 529 



4. Changes Observed within One Interphase 530 



5. Pool Changes 531 



III. Radiation Effects within One Interphase 532 



1 . Effects in Tumors in Vivo 532 



2. Effects in Normal Tissue in Vivo. 534 



3. Effects in Regenerating Liver 537 



4. Effects of Irradiation in Vitro 538 



5. The Question of Differential Effects of Radiation on DNA Synthesis 540 



IV. The Analysis of the Mechanism of Radiation Effect on DNA Synthesis 542 



V. General Conclusion 545 



I. Introduction 



There are several reasons why, during the last decade, an increasing 

 amount of work was directed towards the study of radiation effects on nu- 

 cleic acid metabolism. It has been known for a long time that ionizing radia- 

 tions produce gene mutations, chromosome damage, inhibition of mitosis, 

 and cell death. Indeed the radiation-induced death of higher organisms is 

 usually attributed to depopulation of certain fast growing tissues, such as 

 bone marrow and intestinal epithelium; and radiotherapy of malignant 

 disease is often thought to be based on the differential radiosensitivity (in 

 terms of cell death) of fast growing tissues as opposed to slow- or nongrow- 

 ing tissues. As there is good evidence for the nucleic acid nature of genes 

 and chromosomes, and as there is active nucleic acid synthesis in growing 

 tissues, the study of radiation effects on nucleic acid metabolism — in par- 

 ticular of deoxyribonucleic acid (DNA) synthesis — offered possible answers 

 to a number of important problems, the most acute of them being the mech- 

 anism of radiation-induced cell death. 



However, there is an increasing amount of evidence indicating that gene 



527 



