CARCINOGENESIS 



127 



reflected in the greatly shortened induction period for the hydrocarbons and 

 the significantly greater tumour yield. For sarcomas in rats the same holds 

 true as regards histogenesis and duration of the induction period, but the 

 yield of sarcomas is about the same for the two carcinogenic agents. The 

 essential condition for tumour formation in the case of heavy local irradiation 

 appears to be the induction of specific and progressive vascular changes in 

 the form of endarteritis, periphlebitis and teleangiectasies which in turn cause 

 unstable scars. These vascular changes in rats differ from those induced by 

 repeated thermal burns which in our hands failed to induce tumours locally. 



200 



400 600 



Time (days) 



800 



Fig. 8. The induction of skin tumours in rats by (a) weeldy paintings with DMBA, (b) 

 exposure to an electron beam at doses varying from 2 X 2,300 rads to single doses of 11,000 

 rads, (c) a single dose of 2, 300 rads followed fifteen months later by weeldy paintings with 

 DMBA. 



These observations do not support the hypothesis that in local tumour 

 formation it is the mutagenic effect of radiation directly on exposed cells which 

 is responsible for carcinogenesis, but suggest that this process is rather mdirect. 

 With chemicals, carcinogenesis is more direct in that treated cells or rather 

 their offspring form the tumours. Even here, however, the process involves a 

 passage through various stages and is dependent on systemic factors wliich may 

 promote or inhibit the progress to malignancy. To illustrate this Fig. 9 shows 

 the results of DMBA-paintings of the vulva and vagina of intact and castrated 

 rats. By this means carcinomas are induced in the vulva and sarcomas m the 

 vagina. The rate at which sarcomas and carcinomas occur is about equal m 

 mtact rats, but in castrated rats the vulval carcinomas occur in the same 

 percentage though slightly later, while the sarcomas are not only delayed 

 but very significantly reduced in incidence. In order to test whether, by 

 lowering the immune reactions in the rats, we could speed up the carcino- 

 genesis, we irradiated such rats treated with DMBA either by whole-body 



