124 A. GLUCKSMANN 



during tlie ulcerative phases and the regeneration of the epidermis is due to 

 the immigration of unexposed neighbouring epidermal cells. None of the hair 

 foUicles are left in the exposed areas. The dermal scar is formed largely from 

 the connective tissue accompanying the blood vessels and originally situated 

 below the panniculus carnosus. Figure 2 shows a central section through a 

 lesion 419 days after exposure to radiation: on the right the scar tissue 

 appears hyalmized, almost avascular and acellular and begins to lyse. At the 

 bottom of the picture the elastic fibre layer below the panniculus carnosus 

 can be seen and at the periphery of the scar two vessels are seen just above 

 the panniculus carnosus. The subepidermal elastic fibres are clumped and 

 this change has spread beyond the limits of the original lesion. Above these 

 clumps the epidermis is thickened while the epidermis above the hyalinized 

 scar is keratotic and about to be shed. The peri^^heral epidermis at the other 

 side of the lesion is also thickened and lifted from its basement membrane as 

 Fig. 3 shows. In these regions the absence of cells and lysis in the scar is also 

 clearly seen as well as the thickening of the capillary walls. Still further at the 

 periphery of the lesion marked epidermal thickening is seen (Fig. 4) and the 

 irregular invasion of the peripheral dermal scar by obviously malignant 

 epidermal cells. 



Thus the malignant change occurs in the periphery of the lesion in cells 

 concerned with the repair of the progressive injury caused by radiation and 

 probably in cells whose ancestors were outside the field of radiation. The 

 malignant change occurs after repeated cycles of ulceration and regeneration 

 in the regenerating epidermal cells which are subjected to the adverse con- 

 ditions caused by the radiation-mduced vascular damage. This damage is 

 progressive; it is at first confined only to the immediately exposed superficial 

 vessels but spreads in depth as well as laterally to the deeper vascular 

 plexus which was outside the range of the electron beam. Though this extent 

 and amount of vascular damage may not be the only necessary condition for 

 carcinoma induction, it should be mentioned that with smaller doses of 

 radiation and with a less penetrating beam, i.e. of only 0-3 MeV, we failed 

 to induce tumours. 



In rats the histogenesis of chemically induced tumours resembles that of 

 mice in that the descendants of treated cells ultimately become malignant. 

 There are some differences in details: the process takes longer in the rat; the 

 spacing of hair follicles is greater and they change more independently from 

 the epidermis than in mice and tend to produce basal cell carcinomas; 

 sarcomas occur quite frequently in rats either as separate tumours of starting 

 as sarcomatous changes in the stroma of carcinomas, while sarcomas are rare 

 in mice. 



Irradiation of the dorsal skin of rats is also followed, as in mice, by mitotic 

 inhibition, hyperkeratosis and ulceration. The epidermis as well as the hair 



