16:6/ Molecular Action of Ionizing Radiations 31 1 



6. Indirect Effects on Proteins and Nucleic Acids 



When solutions of proteins and nucleic acids are exposed to ionizing 

 radiations, the changes observed are very similar to those found for 

 dried protein films. However, if the concentrations are low enough, 

 there can be little doubt that many of the effects are indirect, arising 

 from ionizations occurring in the solvent. This is always true for 

 proteins at physiological concentrations. In the case of nucleic acid 

 solutions, and particularly of DNA solutions, the question of direct or 

 indirect effects is not so clear cut. A great deal of evidence supports the 

 direct target theory for DNA in chromosomes and bacteriophages. It 

 shows that ionizations, leading to changes within a critical volume 

 corresponding to about four nucleotides, are sufficient to alter genetic 

 character. It is possible to believe therefore that energy is not trans- 

 ferred very far along the DNA polymer chain. However, the primary 

 effect in living cells could be due to the formation of free radicals in the 

 cellular water in a small volume close to the DNA molecule. 



Because water plays an important role in damage to proteins in solu- 

 tion and may also be significant for DNA changes, effects of ionizing 

 radiations on water have been carefully investigated. The primary 

 process may be represented by 



H 2 0--HO- + H- 



where the dots signify free radicals. Alternative forms are also possible, 

 for example, 



HO + + H- 



These may then recombine in various forms to produce reactive mole- 

 cules such as H 2 2 and H 3 0. All these reactive forms are known to 

 alter proteins and DNA. The probability of producing H 2 2 in water 

 is greatly increased in the presence of dissolved oxygen. 



Many experiments have confirmed that damage to both proteins and 

 DNA in solution is much smaller either in the absence of oxygen or in 

 the presence of a protective agent, which is more likely to react with the 



