^02 General Discussion 



which some evidence was brought by Dr. Lajtha. Recent results 

 obtained by Mazia when studying connection between RNA syn- 

 thesis and cell division suggest that this late radiation effect may 

 possibly be interference with RNA formation. 



The mechanism responsible for DNA synthesis is not known but it 

 is quite probable that its formation necessitates the presence of 

 intact DNA protein molecules and that interference with these and 

 possibly also with the RNA protein molecule are the primary cell 

 lesions. In the mammalian organism unique size and length of a 

 DNA protein molecule much favour uptake of radiation energy. 

 We were told by Prof. Mitchell that he is inclined to consider a macro- 

 molecular lesion of DNA protein to lead to a healing of carcinoma. 



As to the effect of radiation on the DNA protein present in the 

 tissue, it is just ten years since Errera irradiated nucleated red 

 corpuscles and determined the rigidity prior to irradiation and after 

 exposure to a very massive dose of 5000 r or more. He found the 

 rigidity to be reduced. Quite recently, in Dr. Hollaender's Institute, 

 Anderson carried out experiments with diluted homogenates of 

 thymus, determining their viscosity prior to and after exposure. 

 He succeeded in reducing the viscosity after exposure to only 25 r. 

 It may be purely fortuitous or not — it is difficult to tell — ^that the 

 dose that will interfere with DNA synthesis in the thymus, as 

 determined by Ord and Stocken, is about the same as that which is 

 necessary to depress its viscosity, thus to depolymerize thymus DNA. 

 Now I just wonder if it would be possible or profitable to carry out 

 with other tissues, experiments similar to those which Anderson did 

 with thymus. Thymus, of course, has the high DNA content which 

 makes it easier to work with, but it may be possible to take other 

 tissues and to investigate if there is any parallelism between the ease 

 with which deploymerization takes place and DNA formation, and 

 thus also between radiosensitivity. We come here very near to a 

 suggestion made by Prof. Mitchell. He remarked that it is possible 

 that the difference in behaviour of radiosensitive and refractory 

 tumours is due to the fact that the refractory tumours contain DNA 

 of low grade of polymerization ; correspondingly, irradiation cannot 

 easily produce further changes in these. But even if these conclusions 

 were not to be substantiated, it could be quite possible that depoly- 

 merization of the refractory tumour tissue would need a larger dose 

 than that of a sensitive tumour. 



It is thus quite possible that enzymic processes are preceded by 

 cell lesion produced by interference with nucleoproteins. But even 

 if this interference with DNA protein and possibly also with RNA 

 protein should prove to be a very important early step, introducing 

 cell damage, it is not necessarily the first one. 



