DEATH RATE AFTER IONIZING RADIATION 297 



like, and that all diseases have a pathogenesis. (Yes.) Now, are we looking for sometliing 

 beyond these two, or are we looking for various ways in which radiation can affect the 

 pathogenesis of various diseases, which would add up to the various causes of death? 

 (Yes.) Because I thuik one can get mto a muddle if one says I am not concerned with these 

 specific diseases of radiation because I am concerned with the rest. One has got to say I 

 am not concerned with the ways in which radiation affects the pathogenesis of the whole 

 variety of diseases, I am concerned with something else. I don't think anybody is really 

 concerned with that something else. I think we are thorougUy concerned with the way in 

 which radiation affects the pathogenesis of various diseases. Is that right or is that all 

 wrong? 



maisin: In comiection with what Dr. Pocluii says, do you not think that it would be 

 interesting to irradiate locally and thus investigate the importance of local irradiation in 

 ageing? One could irradiate, for example, kidney or Uver tissue, or even intestinal tissue. 



GRAY: So far in this meeting our thoughts have been much occupied with considerations 

 of the factors which influence the survival of proliferating cells. From the point of view 

 of the long-term effects of radiation, possibly including carcinogenesis, it is important to 

 consider the impairment of function wliich the survivors may have suffered, which may 

 interfere with their capacity to play a normal role in their natural environment or in any 

 other environment in which they may find themselves. In this connection I should like 

 to refer to experiments carried out by my colleague, Dr. D. L. Dewey [X-Ray inactiva- 

 tion of inducible enzyme synthesis and the effect of oxygen and glycerol. Nature, Lond. 

 194, 158-160 (1962)] on the capacity of irradiated bacteria to synthesize inducible 

 enzymes. Briefly, Dr. Dewey's experiments show (1) that the maximum capacity of a 

 non-proliferatmg population of Pseudomonas to synthesize the enzymes necessary for 

 the metaboUsm of histidine when this substrate is introduced into the culture medium is 

 depressed by radiation, (2) that the plot of survival of capacity for adaptive enzyme 

 synthesis against dose is strikingly similar to that of survival of proUferative capacity, 

 and (3) that the data impUed an over-riding control of adaptive enzyme synthesis by a 

 structure which may be inactivated by one, or at most a few, ionizing particles, and 

 wliich is of rather considerable size, say around 6 X 10~^® g, wliich is half the size of the 

 structure which controls proliferation. The chemical aspects of the inactivation of both 

 structures have much in common. I would suggest that a simflar situation may exist in 

 relation to the synthesis of adaptive enzymes — among which thymidyUc kinase may be 

 of special interest — in mammalian cells. If the phenomena observed by Dr. Dewey with 

 micro-organisms do have their counterpart in mammahan radiobiology, they might be 

 revealed when the survivors of an irradiated population are called upon to function in a 

 new environment. 



muller: This is tissue culture again? 



GRAY: No. The experiments were made with micro-organisms, viz. Pseudomonas, which 

 were tested for the capacity to synthesize the enzymes necessary for the metabolism of 

 histidine. In bringing these experiments to your notice I had very much in mind the 

 effect of radiation on regenerating liver, in which the adaptive synthesis of thymidyhc 

 kinase appears to be an early step in the transition of the cells from the resting to the 

 proliferating state. 



MAISIN: Do you think that your criteria wfll vary with the tissue that you irradiate? 

 gray: Yes, I do. I suggest that the effect might be observed when the cells which survive 

 an irradiation are called upon to S3TithesLze adaptively, enzymes which are needed in 

 order that the cell should be able to undergo a normal maturation process. 

 10* 



