PHYSICO-CHEMICAL METHODS OF 

 PROTECTION AGAINST IONIZING RADIATIONS 



Peter Alexander and Arthur Charlesby 



Chester Beatty Research Institute, Royal Cancer Hospital, London, and Atomic Energy 

 Research Establishment, Harwell, respectively 



The primary step when a biological system is exposed to ionizing radiations 

 is the utilization of the absorbed energy in a chemical reaction. Since the 

 energy required to produce a biological lesion is often very small and, 

 moreover, since it is initially deposited at random throughout the irradiated 

 material, it would seem to be necessary that the biologically important 

 reaction is with a macromolecule because the proportion of biologically 

 active substances of low molecular weight (e.g. ATP or glutathione) which 

 are changed by irradiation with a few hundred roentgens is negligibly small. 

 We assume, therefore, that the observed lesion is the result of the chemical 

 change of some vital macromolecules present in very limited numbers 

 {e.g. the DNA of the chromosome threads). 



Since in most biological systems radiations having a high specific ioniz- 

 ation are more effective for the same amount of energy deposited than hard 

 X-rays or gamma rays, it seems possible that some morphological structure 

 must be damaged by changing a number of macromolecules close together. 

 Whatever the primary chemical events are, these cannot in general {i.e. 

 excepting perhaps chromosome breakage) be detected in mammals because 

 the doses necessary to produce a biological lesion, of the order of 1 ,000 r or 

 less, cannot bring about a measurable chemical change in vivo. 



In principle there are three general methods of protecting against the 

 initial chemical changes and these may be called physico-chemical, as 

 opposed to physiological protection which interferes with the development 

 of the primary chemical changes into biological end-effects. 



{a) A substance can be added which influences the conversion of the 

 energy taken up in such a way that less chemical change occurs in the 

 'vital' macromolecules. 



{b) Repair by an added substance of the damage produced in the macro- 

 molecule immediately after the primary reaction and before any irreversible 

 change has occurred. In many cases this is not possible since the first re- 

 action is irreversible, e.g. when pure stearic acid is irradiated with alpha 

 rays^ the following chemical change occurs which cannot be 'repaired' 



. CH3(CH2)i5CH2COOH -> CO2 + CH3. (CH2)j5CH3. 



In other cases the primary action may be the loss of, for example, a hydrogen 

 atom, to give a free radical and this can be repaired. Since successive 

 chemical reactions of a molecule changed in this way by ionizing radiations 

 will occur extremely rapidly, the protective substance bringing about the 

 repair must be present before the irradiation. 



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