L. H. GRAY 



tissues of the living animal would normally be in the fully sensitive condition. 

 In several instances, however, this has been shown not to be the case since 

 the administration of oxygen to the animal at the time of irradiation has 

 resulted in an increase in the radio-sensitivity of the tissue in Cjuestion. 

 Thus, for radiobiological damage to growing bone in the tails of young mice, 

 Howard-Flanders and VVright^^ observed that one unit of dose delivered to 

 the animal breathing oxygen was equivalent to 1-35 units delivered to an 

 animal breathing air. Expressing sensitivity by the reciprocal of the dose 

 required to bring about a given degree of biological damage, then relative to 

 the completely anoxic state the sensitivity of the tail bone in animals breath- 

 ing 0-1, 0-2 (air), 0-4, 1, and 3 atmospheres oxygen were found to be 1 -32, 

 1 • 97, 2 ■ 27, 2 • 56 and 2 -67. If for the individual cells from which the damage 

 arises iv = 5 [xM/L, these observations place the mean oxygen tension of the 

 target cells at about 4 mm Hg when the animal is breathing air. 



Howard-Flanders and Pirie^* observed that with regard to the fall in 

 glutathione content of rabbit lens — attributable to an initial damage to the 

 lens epithelium — the effectiveness of a given dose was increased by a factor 

 of 1-24 by oxygen administration. Since corresponding figures for total 

 anoxia and for the maximum level of sensitivity are not known in this case, 

 oxygen tension at the lens epithelium under normal conditions cannot be 

 inferred with any certainty but is probably not far from the mean value 

 inferred for growing bone in the mouse tail. In both these situations, the 

 target cells are separated from their oxygen supply, and a calculation of the 

 diffusion of oxygen from a capillary network at 40 mm Hg on the basis of the 

 observed dimensions of the structures concerned and approximate values 

 of (2o,5 indicates that the inferred oxygen tensions are roughly in accordance 

 with expectation. 



The case of damage to pigment cells at the base of resting and growing 

 hair follicles has been rather fully investigated by Chase and Hunt^^. The 

 observed ratio of maximum to minimum sensitivity was very close to three 

 for both the resting and growing follicle. Interpreted in terms of a cellular 

 response for which w = 3 and K = 5 [i.M/1., or 3-8 mm Hg partial pressure 

 of oxygen, these data indicate that under normal conditions the oxygen 

 tension is about 6 mm Hg at the pigment cells at the base ofthe resting follicles 

 and about 9 mm Hg at the base of the growing follicles. Application of a 

 vascular clamp to stop blood supply to the area only reduced sensitivity to 

 its lowest level if the skin was situated in an atmosphere devoid of oxygen. 

 In normal conditions enough oxygen enters through the skin to provide a 

 partial pressure of around 1 mm Hg at the base of the follicles. 



Scott^*^'^^ observed that when small solid tumours in mice, grown from 

 an inoculum of Ehrlich ascites tumour cells, were irradiated while the animal 

 was breathing oxygen at 1 atm pressure, the effectiveness of the dose in 

 causing tumour regression was increased by a factor of about 1-5. As 

 discussed in my previous lecture (page 76), Deschner and I observed that 

 the same cells growing in the peritoneal cavity had a sensitivity only 

 about 20 per cent above that corresponding to the completely anoxic state. 



From the standpoint of radio-therapy it is important to note that the mean 

 oxygen tension of the tumour cells gro\ving either in solid or ascites forms is 

 lower than the figures inferred for any ofthe normal tissues so far investigated. 



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