350 GENERAL DISCUSSION 



A more homogeneous tissue would have many advantages. Bone has been used a great 

 deal in radiation carcinogenesis work because with bone-seeking isotopes, one can give 

 a very large radiation dose compared with the rest of the body and obtain a high j'ield of 

 tumours. However, this m itself, is not necessarily a good basis for carcinogenesis studies. 



There is another point about wliich I feel more and more strongly. If radiation dose is 

 the only variable in carcinogenesis studies, it is going to be very difficult to mterpret 

 results because dose alters so manj^ things at once. It is a great help if one can work with 

 variables other than the total dose given. The progress in the understanding of radiation- 

 induced thymic lymphoma has come about largely as a result of finding a significant 

 effect of dose fractionation. So far our own fractionation studies on bone with external 

 radiation have not demonstrated any large effect. Another factor which we have 

 mvestigated is that of mechanical injury but we have shown that such injury to the 

 metaphysis has not effect on the tumour yield when radioactive phosphorus is given 

 subsequently. 



One factor which can be varied is the quality of the radiation and it might well be 

 that useful conclusions would foUow from a careful study of the change of RBE for 

 tumour production, of radiations of different quality over a range of dose levels. 



Of course, the direct attack on radiation carcinogenesis is not necessarily^ the best 

 and we ought perhaps, to be adopting a much more fundamental approach. 

 BACQ: Thank you very much. The ideal tissue is stiU to be discovered. Dr. Berenblum? 

 BERENBLUM: Leukaemia is not only an ideal, but actually two ideal systems, mvolving 

 two different leukaemias with mdependent sources of origin: (1) the myeloid system with 

 the bone-marrow as the source, and (2) lymphoid leukaemogenesis, with the thymus as 

 the common source in mice. I believe Metcalf and others are doing some very precise 

 work in investigating the changes m the maturation and development of lymphocytes in 

 relation to the thymus in two strams of animals, one where the leukaemia arises spon- 

 taneously (AKR) and the other in which it does not. 



maisin: There are many organs in wliich we are interested in studying carcinogenesis; but 

 in order to do that one has to give local irradiation, otherwise you do not obtain any 

 local tumours except leukaemia m certain strains. In our strain, for example, we get 

 lymphosarcoma pretty easily but not leukaemia. But to get lymphosarcoma you must 

 just irradiate the ilio-caecal Ijonph nodes. 



BACQ: Do you think that locaUy-trradiated lung would be a better target than bone? 

 maisin: That would be a very good organ to irradiate because, if you are just irradiating 

 one lung and givmg enough radiation you get a tremendous incidence of cancer. It is just 

 the same for the kidney and it is quite enough to irradiate one part of the kidney, you 

 don't need to irradiate aU of it. 



ai,exandek: What animal did you use? (The rat.) Do you get more kidney tumours if 

 you irradiate the kidney locally than if you irradiate the whole animal? (Yes.) So the 

 ascopal factors here are therapeutic and not carcinogenic. 



UPTON: Could not the greater tumorigenic effect of this local renal irradiation be ascribed 

 to a decrease in survival of the animals given whole-body irradiation, which thus inter- 

 feres with the expression of damage? 

 maisin: I guess so, yes. 



UPTON: Without trying to be pessimistic and cynical, I wonder whether there is any 

 ideal tumour system. Cancer is, I thmk a generic term. We are hkely, in trymg to elucidate 

 the mechanism of carcinogenesis, to end up with many mechanisms, it seems to me. It 

 would be wonderful if the results for one tumour could be generalized to everything that 

 is neoplastic, but if this is not the case, then do we not need to study patiently, tumours 

 of many different kinds, however difficult they may be. 



