THE NATURE OF THK IXFIIAL RADLVIMON 

 DAMAGE AT THE SUB-CELLULAR LEVEL 



i'. ALEXANDER 



Chester Beafty Research Institute, Institute of Cancer Research, Royal Cancer 



Hospital, London, England 



AND Z. M. BACQ 



Laboratoire de Pathologic Generale, Universite de Liege, 32 Bd. Constitution, 



Liege, Belgium 



SUMMARY 



A detailed investigation of the changes produced in DNA, when this is exposed 

 to ionizing radiations under a variety of conditions, indicates that radiochemical 

 damage to DNA is unlikely to be the primary event which initiates the processes 

 which eventually result in the death of irradiated cells. Further support for this 

 view is derived from the fact that the sensitivity of the nucleoprotein when 

 irradiated within the cells is approximately the same for cells of widely different 

 radiosensitivities. Attention to the non-genetic components of the cell is indicated 

 by the observation that treatment with iodoacetate before irradiation can in- 

 crease the radiosensitivity of cells seven-fold. Studies of mouse leukaemia cells 

 in tissue culture indicate that chromosome breakage is not an important anatomi- 

 cal lesion for the death of these cells. The hypothesis that interference with the 

 sub -cellular fine structure of the cell consitvites an important primary lesion is 

 discussed. 



As the radiation passes through the cell it deposits energy, part of 

 which is used up to produce ionizations which initiate chemical reactions 

 that cause some of the cell constituents to be chemically altered. There 

 are several steps between the ionization of a molecule and its final 

 chemical state (see "repair" of molecule in this symposium, p. 301) 

 but the time taken for this process is, in vivo, a small fraction of a 

 second, t 



t In model experiments, chemical changes have been observed hours after the irradi- 

 ation is complete. Usually this is due to the fact that solids are treated in which the 

 movement of molecules is limited and radical coml)ination is slowed down. This situation 

 may be encountered in dry biological preparations such as spores or seeds, but does not 

 occur in wet cells. This explains why radicals can be detected by electron spin resonance 

 in dry systems (including seeds, etc.) but no such signal can be observed in irradiated 

 wet cells. 



