lies in the fact that, unlike external irradiation, internal irradiation from deposited 

 radionuclides continues at an ever-changing intensity in a changing cellular environ- 

 ment. Consequently, such questions as the relative importance of dose rate and total 

 dose, with respect to both time and space, are difficult to attack experimentally. 

 There are several lines of evidence indicating that dose rate is a major factor in the 

 induction of osteosarcomas by nuclides that localize in bone^S. In mice, for example, 

 the incidence of these tumors has increased as the second or third power of the ad- 

 ministered dose, and has varied with the time pattern of administration's, 34_ There 

 are other instances of radiation carcinogenesis in which the data also suggest that 

 response varies as a power of the dose'^°. 



An increased incidence of leukemia after the administration of internal emitters 

 has been observed in mice^?. The disease has been reported in a radium patient, who, 

 however, was also exposed to much external gamma radiation^S. in detailed studies 

 of tumor induction in dogs by radium and other radionuclides deposited in the skeleton, 

 no leukemias have been observed and there has been no apparent increase in soft tissue 

 tumors, under conditions that produce bone sarcoma in a high incidence's. 



Reduction life expectancy is an important consequence of radiation from long 

 retained internal emitters, and this response has been observed in populations of mice 

 irradiated at levels that failed to display an increased incidence of neoplasms^'^. At 

 such levels of radiation, it has not been possible to attribute the reduction in life span 

 to any specific degenerative or infectious disease. The animals die with the same 

 variety of pathologic conditions observed in control populations. It is impossible to 

 say, on the basis of our present understanding, whether life shortening from exposure 

 to internal emitters can be attributed mainly to specific pathologic changes or to 

 generalized processes resembling those of aging. 



