132 A. GLiJCKSMANN 



MAYNEORD: Since the experiments I did some time ago with Burrows were quoted, I 

 should hke to mention that we were quite convmced that the tumours arose immediately 

 outside the field of irradiation. It would, of course, be quite impossible to say what dose 

 had been given by scatter. But I remember we gave single doses of the order of 250 r 

 or so and I tliink it is very improbable that the dose was more than 20 r in what seemed 

 to be the site of origin of the tumour, 



CASARETT: I would like to suggest that the promoting factor in carcinogenesis may be a 

 secondary change in the cells of origin. This may be due to small doses of radiation or to 

 some tissue disorder at the site of origin wliich would require bigger doses of radiation. 

 We may be dealing with two different dose problems and two mechanisms of carcino- 

 genesis. In other words, we may have potential cancer cells existing before irradiation 

 and to produce a second change, more radiation must be added. A high dose of radiation 

 causing tissue disorder may be required as the promoting factor so that the full potential 

 of the existing pre-maUgnant cells can be realized. This sort of duplication of mechanism 

 may account for cancers arising outside the field of irradiation in an area which is ser- 

 iously damaged with regard to the supporting tissue. 



ALEXANDER: I would Uke to ask two questions: How strong is the evidence for saying 

 that there must be at least two quite different pathways: the one foUowuig whole-body 

 irradiation, where the tumour mduction is higlily dependent on the genetic make-up of 

 the animal and where there does not seem to be any a 'priori demand for severe or readily 

 detectable tissue injur}^ and the second one from locaUzed radiation where as far as one 

 can see genetic make-up plays a relatively minor role and where tissue injuries form the 

 key point. I wonder whether this is a reasonable summary of the present situation? 



My second question: when you gave doses of radiation which reduced the carcino- 

 genicity of the hydrocarbons, did those doses produce detectable damage or not? 

 GLUCKSMANN: Your Summary is very reasonable. The doses of radiation we gave to the 

 rat skin before DMBA caused depUation. 



ALEXANDER: I think Dr. Hochman at Jerusalem reported that doses of 700 or 800 r of 

 X-rays reduced the effect of DMBA and this dose induced no obvious skin damage. 

 MOLE: I want to object to Dr. Gliicksmann's conclusion: if he uses only doses of radiation 

 that produce severe damage, he cannot conclude that severe damage is necessary. 

 GLifcKSMANN: That is obviously a good point, but we did try smaller doses and did not 

 get any effect. 



GRAY: It seems to me that it may not be correct to sum up tliis morning's discussion by 

 saying that in order to produce tumours you must produce gross damage and that the 

 tumour cells need not necessarily have been irradiated. I tliink Dr. Gliicksmann said that 

 the surest way of producmg tumours is by way of gross damage and that very likely, the 

 tumours arise from cells which have not been irradiated. But I would hke to know what 

 Gliicksmann thinks about the type of experiment done by Bond and his collaborators, 

 because I thuik we certainly ought to bear in mind a certain possible mechanism which 

 might be distinct from the one you have been talking about. With the experiments of 

 Shubik et al. and with those of Bond et al. we have definite evidence that you can get 

 tumours at low doses and that they arise in irradiated cells. Just to keep the balance, I 

 wonder if you would comment on the experiment. Am I wrong in my interpretation? 

 GLTJCKSMANN: I quite agree with you that there are different mechanisms of carcino- 

 genesis by irradiation. The breast cancers, like the ovarian cancers, can be induced under 

 certain hormonal and other systemic conditions by small doses of irradiation, and they 

 arise in irradiated cells. These systemic conditions are difficult to analyse and I have 

 concentrated on the mechanism of local effects of radiation in carcinogenesis. Here the 

 conditions are different in that the primary carcinogenic effect of radiation is on the 



