STUDY OF IIIi: IMI-UENCI-: OF OXYGKX OX RADKO-SFASniNITY 



values still. It tlic (cIls have no oxygen available to them, they obviously cannot 

 respire. 



Dr. McCIai.ia m : 11 We are studying oxygen in equilibrium, are we studying the 

 actual oxidation-reduction potentials of the system? Could it be that Redox poten- 

 tials of enzyme systems rather than the dissolved oxygen control the radio-sensitivity 

 of the cells which you have been observing? 



Dr. Gray: I doubt if one can exclude sucii an inlerijrctalioii in the most general 

 sense that radio-sensitivity is related to the Redox potential of some unspecified 

 enzyme system. I shall have more to say about this tomorrow. In certain cells I 

 think the evidence is strongly against the influence of oxygen on radio-sensitivity 

 being mediated through the Redox condition of the cytochrome enzymes. This has 

 been specifically tested in the cases of two bacteria and one yeast, by comparing the 

 influence of oxygen on wild type cells and haemin-deficient mutants. In the experi- 

 ments of Moustacchi* it was estimated that the amount of respiratory enzyme present 

 in the haemin-deficient mutant strain was less than three parts per thousand of that in 

 the wild type. The two strains, however, show some influence of oxygen on radio- 

 sensitivity. 



Mr. van den Brenk: May I ask Dr. Gray if he thinks that in experiments with E. coli 

 which Hollaender reported, a protection by cysteamine over and above that evident 

 by simple anoxia was due to the fact that the nominally anoxic cells still contained 

 a small amount of residual oxygen? 



Dr. Gray: If I am thinking of the same experiment as you are*, then there would 

 appear to be some doubt concerning the experimental facts of the situation. Marco- 

 vich^ has made many experiments with cysteamine and a strain of bacteria, which 

 were nominally those used by Hollaender, but was never able to obtain a better 

 degree of protection than by simple anoxia. I am afraid I have no suggestion as to 

 how this apparent discrepancy is to be resolved. 



Mr. van den Brenk: Do you suspect that in the transfer of oxygen from the inter- 

 cellular fluid to the inside of the cell, that it is just a question of physical diffusion 

 gradient, or that there might be energy involved as a transfer process? 

 Dr. Gray: I wish that a biochemist could tell us the answer to that question. For my 

 part, I do not know the answer. In bacteria the question has been fairly carefully 

 examined by Longmuir* who measured the Oq^ of extracted cytochrome oxidase and 

 of the same enzyme in the intact bacterial cell as a function of oxygen concentration. 

 In most cases these were the same, but he did find a Qq^ which was lower for the intact 

 bacillus in the case of Afegaterium. This he provisionally ascribed to a diffusion barrier 

 offered by the cell membrane. I am not sure whether he still holds to this interpreta- 

 tion. He found no evidence of a similar diffusion barrier offered by the cell wall of 

 liver cells. It would be very desirable to have accurate data for a wide variety of cells, 

 since we are now concerned, from the radiobiological standpoint, with extremely low 

 concentrations of oxygen, and barriers which might hitherto have been regarded as 

 unimportant may in reality be significant. 



REFERENCES 



iAlper, Tikvah Brit. J. Radiol. N.S. 27 (1954) 50 



2ADLER, H. I. Radiation Res. 9 (1958) 451 



^Adler, H. I. and Stapleton, G. E. Radiation Res. 9 (1958) 84 Abstr. 



*KuNKEL, H. A. and Schubert, G. Proceedings of the Second International Conference on 



the Peaceful Uses of Atomic Energy, Geneva, 1958 — in the press 

 ^MousTACCHi, E. Ann. Inst. Pasteur 94 (1958) 89 

 'Hollaender, A. and Stapleton, G. E. Proceedings of the First International Conference 



on the Peaceful i\'ies of Atomic Energy, 11, Geneva, 1955, p. 311 

 ^Marcovich, H. Ann. Inst. Pasteur 93 (1957) 456 

 ^Longmuir, I. S. Biochem.J. 57 (1954) 81 



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