INITIAL RADIATION DAMAGE AT SUB-CELLULAR LEVEL 15 



Both cross-linking and degradation have been observed in the DNA 

 in heavily irradiated cells. The DNA in thymocytes and in mouse 

 leukaemia cells suffers only degradation and no evidence for cross- 

 linking, while cross-linking predominates when the sperm of fish are 

 exposed to sparsely ionizing radiations (Alexander and Stacey, 1959). 



Irradiation ivith y.-raijs. The effect of densely ionizing radiations such 

 as a-rays from polonium is initially less complex, f since only degrada- 

 tion is observed, the efficiency of which is independent of conditions. 

 Quantitatively, a double strand of DNA is severed every time it is 

 traversed by an a-particle. This corresponds to one "double break" for 

 every 650 eV of energy deposited (Alexander et al., 1961). 



Biological implications. These studies show that DNA is drastically 

 altered by radiation. Some of the effects produced are qualitatively 

 different in the presence of oxygen, but there is no evidence to suggest 

 that oxygen influences the total number of molecules aff"ected. 



a-rays are slightly more effective than sparsely ionizing radiation 

 (650 eV as opposed to 800 eV) in producing main-cham scission (double 

 breaks) and this is therefore a radiochemical reaction in which the 

 relative efficiencies of different radiations are at least qualitatively the 

 same as for biological effects. It is tempting therefore to speculate that 

 double breaks may constitute an important primary lesion. But this 

 hypothesis fails to provide an explanation for the enhancement of 

 radiation of sparsely ionizing radiations by oxygen which does not 

 interfere with main-chain scission, but only prevents cross-linking. 

 Another difficulty is that one would expect cross-linking to be at least 

 as effective as main-chain scission in rendering DNA biologically useless. 

 If damage to DNA were an important primary lesion then the combined 

 effect of cross-linking and main-chain degradation must be considered. 

 On this basis, electrons are more efficient in inactivating DNA molecules 

 than a-rays. This is confirmed by irradiation of transforming principle 

 for which the inactivation dose increases with increasing LET (Fluke 

 etal, 1952). 



DAMAGE TO MEMBRANES AND INTRACELLULAR BARRIERS 



It seems that on the basis of radiochemical studies, we have to reject 

 the view that damage to DNA or DNA-protein constitutes the primary 



f a-rays are always accompanied by less densely ionizing S-rays which comprise some 

 20 per cent of the total energy deposited by a-rays. These 8-rays give rise, in the absence 

 of oxygen, to cross-linking and this complicates the results obtained with a-rays. 



/ 



