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RADIOBIOLOGICAL MECHANISM AT THE 

 CELLULAR LEVEL: Lines of investigation 

 which have been opened up by the recent technical 



developments 



L. H. Gray 



British Empire Cancer Campaign Research Unit in Radiobiology, 

 Mount Vernon Hospital, Northwood, England 



We have to confess that though the action of X-rays on Hving cells has been 

 studied for more than sixty years we are still extremely ignorant of the 

 mechanisms involved. 



The formation of ions and excited molecules represents a gross local 

 disturbance from the molecular standpoint. We can confidently assert from 

 our knowledge of the physical processes involved that some 300,000 such 

 disturbances occur in a cell 10 microns in diameter exposed to 100 rads of y 

 radiation, but with a few exceptions confined to studies with seeds, these 

 disturbances have not been directly observed in living cells. Radiobiologists 

 have hitherto had to rely entirely on the cell as its own indicator of the 

 changes initiated in it by ionizing radiation. Since the initial disturbances 

 are approximately randomly distributed over all cell functions, and the 

 materials which serve these functions are undergoing continuing synthesis, 

 it is to be expected that the great majority will escape detection. Aberrant 

 molecules may either be rejected or, if built into the permanent structure, 

 may cause so slight a disturbance of function as to escape our comparatively 

 crude methods of analysis. The forms of radiobiological damage known to 

 us at present, therefore, do not constitute a representative cross-section of the 

 ' built-in ' defects, still less of all defects sustained by the irradiated cell, but are 

 a highly selected group. The basis of selection is immediately evident when 

 we consider some of the better known forms of radiobiological damage. 



Damage to the Genome — Sub-microscopic 



The uniqueness of every element of the genome of a haploid cell makes almost 

 any kind of error in this material detectable by the highly developed tech- 

 niques of genetic analysis. The linear dose dependence and absence of dose- 

 rate dependence so frequently observed point to gene mutation as being 

 initiated monotopically, i.e. as a single event process. After many years of 

 douljt it now appears to have been established for Xeurospora h\ the work 

 of Giles and de Serres^ and for Drosophila by Mullcr and Oster-, that ionizing 

 radiation may induce mutation back to the wild type at a locus which had 

 previously undergone mutation under the influence of radiation. This does 



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