130 A. GLtJCKSMANN 



shortening of the induction period with irradiation. For chemical carcinogenesis we have 

 found that continuous presence of chemicals in the form of injected deposits can shorten 

 the induction period as compared with weekly apphcations. For both forms of application 

 we found that a change in the hormonal pattern of the experimental animal can shorten 

 or prolong the induction period. In radiation carcmogenesis the latent period is always 

 long and tliis agrees with almost all other observations. Similarly the doses are fairly 

 large, except if there are some predisposing factors such as the injection of silicates 

 by Lacassagne and by Burrows et al. Unless you change the biological system, you 

 cannot cut down the dose of local radiation nor shorten the induction period. 

 CURTIS: Yesterday we talked a great deal about the two-stage hypothesis of tumour 

 induction in the case of leukaemia. Fractionation of the dose into two, three or four doses 

 of radiation separated by one or two week intervals proved much more effective than a 

 single dose and this with other facts discussed yesterday, indicates that apparently this 

 is a two-stage phenomenon. Have you done sometliing like tliis in the skin and is there 

 any suggestion of a similar two-stage phenomenon in the skin? 



glucksmann: I did the classical experiment of following a smgle dose of radiation from 

 an electron beam with weekly apphcations of croton oil to the skin of mice. I failed to 

 produce more papillomas in irradiated than in control mice and never got a fully mahg- 

 nant tumour, i.e. a carcinoma or sarcoma. Shubik et al. reported a similar experiment some 

 time ago and got more tumours after previous jS-ray exposure with croton oil. Unfor- 

 tunately they did not do any histology and we do not know whether these tumours were 

 only papillomas or mahgnant. They used a smaller dose of radiation than we did. In our 

 experiments cancer formation seems to occur in regenerating ceUs rather than in the 

 offspring of directly-treated cells and we have thus conditions very different from the 

 chemical carcinogenesis of the skin where the two-stage phenomenon apphes. 

 gray: In relation to Shubik's experiment: though he got papUlomas and no sarcomas or 

 carcmomas, his results are quite clear-cut. He had three groups of mice: those given a 

 dose of 800 rads of ^-rays had no papillomas, those treated with croton oil alone had few 

 papillomas while those given 800 rads and subsequently painted with croton oil had a 

 great many papillomas. I was very interested in this experiment because if there is a 

 specific effect of irradiation in inducing tumours, I tliink perhaps the use of low doses of 

 radiation Avhich do not cause cell destruction, followed by a promoting agent like croton 

 oil might be a good way of finding out about it. 



There is some evidence in the literature of some kind of specific initiating act in 

 tumour formation in the experiments of Bond and Cronkite with breast tumours in rats. 

 There is a hormonal factor involved. But they have shown that the natural incidence of 

 breast tumours assayed at one year is extremely Ioav, that there is an mcrease ua tumour 

 yield with doses fi-om 25 r upwards and that the tumours occur m irradiated zones only. 

 When they segmented the breast for irradiation, the tumours appeared in the irradiated 

 zones only. Whether this is an initiation of tumour mduction or a hastening of some other 

 process, it is necessary to irradiate the cells in wliich the tumour arose and in some 

 cases the doses were as low as 25 r, though the dose range was from 25 to 800 r. 

 GLUCKSMANN: The situation for the breast is very similar to that for the ovary; irradiation 

 is necessary but hormonal factors come m at some stage aU the time. 

 cottier: You showed pictures of the initial necrosis of skin after heavy radiation. Were 

 you able to foUow whether the regenerating epithelium originates from witliin the 

 irradiated field or perhaps also from an outer irradiated zone or were there some follicles 

 or single cells left? 



glucksmann: All the folhcles and the whole epidermis were killed and the vascular 

 changes extended beyond the iiTadiated region. Thus even the first regeneratmg tissue 



