18 



THE INFLUENCE OF OXYGEN ON THE RADIO- 

 SENSITIVITY OF CELLS AND TISSUES 



L. H. Gray 



British Empire Cancer Campaign Research Unit in Radiobiology , 

 Mount Vernon Hospital, jYorthwood, England 



Many cells and tissues are much more damaged by exposure to ionizing 

 radiation if they are situated in an aerobic environment at the time of irradia- 

 tion than if they are deprived of oxygen. One of the earliest clear-cut 

 examples of this was seen in Ascaris eggs by Holthusen^ who observed that 

 the dose of X-rays required to prevent the eggs hatching was three times as 

 great when the eggs were anaerobic as when they were aerobic at the time of 

 irradiation. Subsequently, many other kinds of response to radiation have 

 been tested in a variety of cells. In the great majority, it has been found that 

 sensitivity is positively correlated with the availability of oxygen to the cells 

 at the time of irradiation {Table 1, Section A). The entries and references in 

 Section A of Table 1 are only a selection from the very large number of investi- 

 gations which have revealed a positive dependence of radio-sensitivity on 

 oxygen tension. 



Section B of the Table 1 cites a number of instances in which little or no 

 oxygen dependence has been reported, and two systems in which greater 

 radiation damage in the absence of oxygen has been reported. These systems 

 are phage and calf thymus DNA irradiated in dilute aqueous suspension and 

 assayed immediately for plaque-forming ability or for loss of structural 

 viscosity respectively. The reverse oxygen effect is very well established in 

 the case of the phage-. Nevertheless, if either the phage or the DNA (des- 

 oxyribose nucleic acid) is allowed to stand for a period of time before assay 

 the over-all damage is greater if oxygen has been present at the time of 

 irradiation. On account of the comparative rarity and corresponding 

 importance of exceptions, some examples are included in Section B which are 

 commonly reported as oxygen independent, though a careful scrutiny of the 

 published data shows this not to be the case (reverse mutation to strepto- 

 mycin independence in Escherichia coli B/r*), and one example, namely 

 dominant mutation induction in mouse sperm, in \vhich the assignment rests 

 on the observation that the effect was not diminished by hypoxia. Real 

 oxygen independence could only be considered as established if, in addition, 

 the administration of oxygen to the animals at the time of irradiation was 



* The data presented by Anderson^ show that anaerobiosis resuhs in a dose reduction 

 factor for reverse mutation to streptomycin independence of about 1-3. Dr. Gunther has 

 pointed out to me that the scatter of points in Anderson's Figure 2, p. 343, is such that the 

 dose reduction factor might be considerably larger, especially if observations at the lower 

 dose levels are considered more reliable for the estimation of mutation rates than those at 

 higher dose levels where the interpretation may become complicated by cell death. 



152 



