CARCINOGENESIS 131 



was subsequently shed and the repair coidd be brought about only from outside the 

 irradiated zone, i.e. in the case of the epidermis from neighbouring unirradiated epidermis. 

 gkay: But if you are giving 12,000 rads in the irradiated zone, the periphery surely might 

 have had 100 rads. 



glucksmann: Boag's paper dosimetry (Fig. 1) shows a very sharp cut-off of the radiation 

 in depth and laterally. Even if some peripheral cells survived irradiation and participated 

 initially in the regeneration, the progressive vascular change with the repeated cycles of 

 regeneration and sloughing would effectively remove most, if not all, of the peripheral 

 cells. 



biartinovitch: Have you tried to graft irradiated epidermis to unirradiated dermis or 

 alternatively grafted unirradiated epidermis on the irradiated region? 

 GLTJCKSBiANN: No, we have not done this. 



chase: We have not done carcinogenic experiments as such, but have some incidental 

 pertment observations indicatmg that you have to get an ulcer before you obtain 

 tumour formation. We exposed skin to sUghtly lower doses m the 800 to 1,000 r range 

 and repeated the doses several times. Though accumulating a considerable dosage, we 

 did not get ulceration and no tumours. We then gave a dose of 1,800 to 2,000 r, got 

 ulceration and after repeating the dose we obtained papUlomas and then maUgnant 

 tumours. 



GLTJCKSMANN: I should mention one other thing: you can get necrosis of dermal tissue and 

 its resorption and replacement by regenerating tissue without apparent ulceration and a 

 similar replacement can take place also in the epidermis. Fundamentally this is still 

 cellular death and repair whether it takes place at the surface or underneath. 

 BERENBLUM: In the earlier days of skin carcinogenesis I was always impressed by the 

 fact that the more potent carcinogens all produced hyperplasia and it was therefore 

 assumed that the hyperplasia was secondary to some sort of damage. Everything fitted 

 very well and when one extended this work to give a single painting of a carcinogenic 

 hydrocarbon and then croton oU, there appeared to be a similarity between the degree of 

 damage produced by the carcinogen and its effectiveness as an initiator. But this changed 

 when Salaman introduced urethane — perhaps the most potent initiator of all — which 

 produced no hyperplasia, and no damage to the epithelium. W^hat is more, one can inject 

 urethane subcutaneously and then apply croton oil to the skin, and still get tumours. We 

 have now become very cautious about assuming that the component wliich has anything 

 to do with damage is that responsible for carcinogenesis. Now, I reahze that with 

 radiation it is very difficult to set up a group of experiments at the same time. But if you 

 have to give a single dose, it has to be big enough to produce a certain damage. On the 

 other hand, if you give multiple doses, it wUl compHcate the experiment to such an 

 extent that you cannot do it. I am just wondering whether the damage produced is 

 really as critical as it appears from your experiments, or whether, if one could design a 

 suitable type of experiment where the radiation per unit time were so low, one could not 

 get carcinogenesis without damage to the epithelium. 



GLUCKSMANN: These experiments have been done to a certain extent with /3-rays by 

 Henshaw et al. The answer, I tliink, was that up to 25 reps daily he did not get any visible 

 damage or tumom-s. With doses above 50 reps per day he gets damage and ultimately 

 tumours. For local irradiation it seems that you have to have some degree of damage 

 before getting carcinomas or sarcomas. 



brixkman: You could protect the dermis chemically against radiation damage without 

 protectmg the epidermis. Tliiosulphate protects the dermis without protecting the 

 epidermis and this might help in differentiating your problem. 

 GLtfcKSMANN: Thank you, this is a very good suggestion. 



