CARCINOGENESIS BY IONIZING RADIATIONS 1153 



the latter were actually produced by X irradiation. No such doubt 

 exists as concerns tumors in bones which are particularly susceptible, 

 notably if inflamed; but even apparently normal bone, when subjected to 

 massive irradiation, may undergo a neoplastic change (Spitz and Higin- 

 botham, 1951). 



Experimental induction of neoplasms in animals by X irradiation 

 began eight years after the first observations in man. The procedures 

 used imitated the conditions of exposure in man. The early literature is 

 surveyed in Table 18-1. In his monograph, "Les Cancers Produits par 

 les Rayonnements Electromagnetiques," Lacassagne (1945b) discusses 

 extensively the early literature which will not be fully reviewed here. 



Marie et al. (1910, 1912) and Clunet (1910) gave repeated doses to rats 

 estimated by Lacassagne to be about 600 to 2000 r during four to twelve 

 months and so induced spindle-celled sarcomas. For many years remark- 

 ably little use was made of this novel type of carcinogenesis. Bloch 

 (1923, 1924) and Schurch (1930) induced carcinoma in the rabbit by 

 repeated exposures to X radiation. Subsequent work on the induction 

 of cutaneous sarcomas in guinea pigs (Goebel and Gerard, 1925), cutane- 

 ous carcinomas in mice, and bone tumors in rabbits is surveyed in Table 

 18-1. 



The tumors of the skin were induced by relatively large doses of ion- 

 izing radiations at the sites of exposure. It is doubtful if any species 

 would resist this type of carcinogenesis. The next important observa- 

 tion was that, following total-body exposures, neoplasms, leukemias, 

 ovarian, mammary, and other tumors appeared in different organs. 

 Mammary tumors were also induced in rats and rabbits. Subsequent 

 research aimed to elucidate the pathogenesis and morphogenesis of the 

 induction of internal neoplasms and to determine the relevance of 

 observations made in one species to the animal kingdom at large. At 

 first, single or a few large doses of X radiation were used in these studies ; 

 later, also 7 radiation and chronic exposures. A large-scale chronic 

 exposure study in mice, guinea pigs, and rabbits using 7 radiation of 

 radium was carried out by Lorenz et al. (1947). In mice there was a 

 marked increase in the incidence of leukemia in the females of the groups 

 exposed to 4.4 and 8.8 r (8 hours) daily (Fig. 18-2), an even greater 

 increase in the incidence of ovarian tumors, and a slight increase in 

 incidence of breast and lung tumors. In guinea pigs, there was an 

 increase of mammary tumors, and in rabbits of uterine tumors. This 

 and other recent work are surveyed in the sections which follow. 



NEOPLASIA INDUCED BY RADIOACTIVE SUBSTANCES 



While experimental induction of cancers by X irradiation followed, that 

 by radioactive substances preceded the observations on man. Lazarus- 



