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CARCINOGENESIS BY IONIZING RADIATIONS 1157 



caused in man by radioactivity, but they may disclose sensitivities to 

 neoplastic changes. 



Roussy et al. (1934) were first to report on the experimental induction 

 of tumors by thorium dioxide (thorotrast) by intraperitoneal injections of 

 this substance into rats. Subsequently, several workers induced sar- 

 comas by subcutaneous injection of thorium dioxide in rats and mice 

 (Roussy et al., 1936; Selbie, 1936; Miyamota, 1939; Prussia, 1936; 

 Bogliolo, 1937, 1938; and Selbie, 1938. The tumors so induced by 

 Selbie were spindle-cell sarcomas (six), osteosarcomas (three), and one 

 hemangioendothelioma. This recalls the extraosseous bone tumors 

 induced in man by X irradiation and the hemangiosarcoma induced by 

 radium. Bogliolo induced tumors in all of twenty-three rats that had 

 been given subcutaneous injections of thorotrast. In guinea pigs 

 Foulds (1939) induced sarcomas and a carcinoma by repeated injections 

 of thorotrast in the nipple after a latency of three years. Andervont 

 and Shimkin (1940) confirmed the induction of sarcoma and hemangioma 

 in mice by subcutaneous injection of this substance and called attention 

 to the absence of lung tumors in their mice, even though radioactive 

 particles were demonstrated in the lungs throughout the course of the 

 experiment and the strain of mice used was highly susceptible to lung 

 tumors. Dunlap et al. (1944) fed rats each with 100 ^g of radium and 

 produced osteosarcomas in nine of thirteen animals. 



The statements of Roussy and Guerin (1941), and later of Willis 

 (1948), that tumors may appear in human beings who had been given 

 thorotrast for diagnostic purposes, proved valid. The use of thorotrast 

 is relatively recent and many years may elapse before tumors develop. 

 An endothelial sarcoma developing in the liver of a seventy-year-old 

 woman, following thorotrast injection, was described by MacMahon 

 et al. (1947). Thorotrast taken up by macrophages was demonstrated 

 microscopically in tissue sections, and this phagocytic activity was cor- 

 related with radioactivity. In spite of the wide use of thorotrast for 

 diagnostic purposes, no other case of endothelial sarcoma of the liver 

 was reported, even though thorotrast is retained by reticuloendothelial 

 cells. Hence, the possibility is considered that this tumor was spon- 

 taneous. All cells of the liver are relatively resistant to induction of 

 neoplasia. The observations of MacMahon and those made earlier by 

 Ross suggest that endothelial cells are the most susceptible elements of 

 this organ. Many radioactive heavy metals entering the body are 

 retained in the liver, notably those given in suspensions or colloids. 

 Tissue containing 1 per cent thorotrast by weight is estimated to receive 

 approximately 3000 rep in ten years (Evans, 1950a, b). 



Sarcoma of the maxilla developing nine years after intravenous injec- 

 tion of mesothorium was described by Gricouroff et al. (1943), and a 

 solitary plasmocytoma of the humerus in a mesothorium worker by 



