CARCINOGENESIS 125 



follicles are shed and epithelial healing is due to the immigration of neigh- 

 bouring epidermal cells. The dermal changes resemble those in the mice in 

 that an unstable scar is produced, but differ in that the changes are between 

 keloidal and thin-fibred states instead of between hyalinization, lysis and 

 thin-fibred scars. In either case the keloidal or hyalinized tissue is replaced 

 by a cellular tissue which in turn becomes keloidal or hyalinized until in the 

 rat this tissue undergoes a sarcomatous change. The instability of the scar 

 tissue can be traced in both species to progressive vascular injury manifested 

 by endarteritic and teleangiectatic vessels of even the deeper plexus and 

 causing late ulcers. At the edge of these ulcers papillomas (Fig. 5) and 

 carcinomas (Fig. 6) occur. As in the mouse these malignant changes are 

 likely to occur in cells whose ancestors were not exposed to radiation. The 

 majority of tumours in the rat are sarcomas which arise in or close to the 

 panniculus carnosus which was outside the range of the electron beam and 

 which as in the mouse becomes involved in the lesion only very much later. 



Table I. Induction of papillomas, carcinomas and sarcomas in the dorsal skin of 

 rats by DMBA, by localized irradiation and by irradiation followed after fifteen 



months by DMBA 



Number Percentage incidence of 



Treatment of rats Papillomas Carcinomas Sarcomas 



DMBA 68 15 84 37 



Radiation 95 3 8 32 



DMBA -t- radiation 15 20 40 



Thus in mice and rats radiation-induced cancers arise in regenerating 

 tissue rather than in the descendants of treated cells as in the case for 

 chemically induced tumours. This "indirect" action of radiation as compared 

 with the more "direct" effect of chemical carcinogens is reflected in the 

 duration of the induction period and the tumour yield. 



In the dorsal skin of mice a dose of 8,000 rads given at 0-7 MeV over a 

 circular field of 1 cm diameter produced only four carcinomas in 27 mice 

 surviving for 400 days. The weekly application of benzpyrene to 48 mice 

 resulted in 48% carcinomas and an additional 38% of papillomas in a period 

 of three to five months (Fig. 7 ). With smaller single doses of 4,000 rads or with an 

 electron beam generated at 0-3 MeV no tumours were found. A single dose of 

 4,000 rads at 0-7 MeV followed by weekly applications of croton oil failed to 

 increase the incidence of papillomas over that obtained with the croton oil 

 painting alone. 



In rats the tumour yield following irradiation, or the application of DMBA 

 to the dorsal skin, is given in Table I. In the group of irradiated animals are 



