122 A. GLUCKSMANN 



for tumour i^roduction. On the other hand, an unirradiated thymus grafted 

 into an irradiated thymectoniized mouse may produce tumours (Kaplan and 

 Brown, 1954). The relation of radiation effects to other systemic actions in 

 these carcinogenic events are far from being understood. It might be thought 

 that the understandmg of carcinogenesis by direct local action will be less 

 difficult. 



Radiation is known to cause mutations in cells and the somatic mutation 

 theory is one of the popular concepts of cancer. The assumption that radiation 

 causes cell mutation and thus cancers is obvious and might be considered the 

 simplest theory of direct cancer induction: cells with suitable mutations 

 proliferate into visible tumours. An alternative hypothesis is the possibility 

 that radiation causes excessive changes in the irradiated tissues and that 

 these conditions cause secondarily cancerous changes m irradiated or even in 

 unexposed cells. I propose to devote most of my time to radiation changes 

 induced by localized radiation and to compare the process of radiation- 

 mduced carcinogenesis in the skin with that following the application of 

 chemical carcinogens. 



For chemical induction of skin cancers we painted mice once weekly with 

 a 1% solution of benzpyrene in acetone, and rats, also once weekly, with a 

 1% solution of 9, 10-dunethyl-1.2-benzanthracene (DMBA) in acetone. The 

 irradiation experiments were carried out in collaboration with Dr. J. W. 

 Boag and made use of an electron beam generated by a van de Graaff linear 

 accelerator. This arrangement is very suitable for irradiating the skin of 

 mice and rats, since the depth and area of the irradiated tissue can be 

 defined very clearly and the total radiation energy is absorbed in the skin. 

 The irradiation was given through the intact hair coat, the field defined by a 

 saddle-like lead shield and the depth regulated by the voltage at which the 

 irradiation was given. Figure 1 illustrates the definition in depth and area of 

 the beam by means of paper dosimetry. On the right is the image of the 

 electron beam passing at right angles through photographic paper in the 

 centre of the field. For A the field size in mice is a 1 cm circle and the depth 

 of blackening related to 0-7 MeV. For rats a circular region of the dorsal skin 

 of 2-5 cm diameter was exposed at 1-0 MeV. B shows the image of the beam 

 in the photographic paper in a similar position to A, while in C the top edge 

 of the photographic paper is shaped to resemble the curvature of the dorsal 

 region of the rat. On the left hand side of the picture a number of sheets of 

 photographic paper were clamped together and exposed to an electron beam 

 generated at 1-0 MeV. The definition of the area and the sharp cut off of the 

 radiation energy at depth are clearly evident. 



We shall start with a comparison of the histogenesis and then discuss 

 tumour yield and duration of the induction period for chemical and radiation 

 carcinogenesis, first in mice and then in rats. The application of benzpyrene 



