CARCINOGENESIS BY IONIZING RADIATIONS 1183 



girls had osteogenic sarcomas, all of whom died before 1930; four are still 

 known to be alive, suffering from a crippling bone lesion, probably radia- 

 tion osteitis with pathological fractures; and three died from epidermoid 

 carcinoma that started in the mucosa of the accessory sinuses of the head. 

 Since this type of carcinoma is rare and no other carcinoma was found in 

 this small group, their relation to the ingested radioactive materials 

 seems highly probable. Mainland's observations gave impetus to the 

 study of experimental induction of bone tumors, and to establish factors 

 governing the induction of this tumor, such as the dose levels of tumor 

 induction, permissible maximum exposure to radiation, and methods to 

 increase the elimination of radioactive substances from the body. 



In persons with chronic radium poisoning who have developed osteo- 

 genic sarcomas, the radium content varied from a few to over 20 ^g. 

 Analysis of the radium content of bone of a patient with a fibrosarcoma 

 made after approximately fifteen years of exposure showed an average of 

 1.5 X 10 -9 g of radium per g of dry bone, delivering approximately 1 rep 

 per day per g of bone (Evans et al., 1944; Evans, 1950a). Average dose 

 values are of little significance unless the distribution pattern is known to 

 be uniform. This is not the case, however, since the radium is distributed 

 at discrete points throughout the bone. 



Recent investigations of Evans (1950a) showed that persons who 

 had received radium only and who contained from 0.3 to 22 ^g of stored 

 radium were free of bone tumors up to thirty-four years. A clinical pic- 

 ture similar to that of the luminous dial painters was produced in these 

 patients by approximately five to ten times as much radioactive material. 

 The compound ingested by the dial painters contained mesothorium, an a 

 emitter with a half life of 6.7 years. When Martland's cases were 

 investigated, mesothorium had already decayed many half lives and 

 only the stored radium was determined. Mesothorium may have been 

 involved in all cases of irradiation injury in which the stored radium was 

 less than 5 ^g- Accordingly, the maximum permissible value of 0.1 ng 

 of radium may have a safety factor of 50. The permissible doses of the 

 various elements given were established before these findings were known. 



Experimental Production of Bone Tumors. The first bone tumors in 

 man and experimental animals were induced inadvertently. Lacassagne 

 and Vinzent (1929), irradiating chronic inflammatory lesions of rabbits, 

 produced an osteosarcoma and a periosteal sarcoma. Lacassagne and 

 Nyka (1937), attempting to induce tumors of the hypophysis with radon, 

 caused the development of bone tumors of the sella turcica. The 

 sequence of changes noted has been necrosis, revascularization, callus 

 formation, and cancerization. The numerous studies made subse- 

 quently, including those with fission products, have been detailed in the 

 section on corpuscular irradiations. It is evident from the observations 

 described that osteoblasts are highly susceptible to neoplasia induction. 



