RADIATION-INDUCED BONE TUMOURS 153 



difference in response, although there is some indication that the bone 

 tumours appear slightly earlier with the repeated injections. 



Fibrosis was not a constant finding in the bones of these rats and, when 

 observed, it consisted of no more than a localized area of rather loose connec- 

 tive tissue in the marrow associated with some surrounding marrow aplasia. 

 There was little evidence of the dense fibrotic change described by some other 

 workers (Lisco, 1956; Jee et al., 1957) and sometimes assumed to be an 

 important factor in bone tumour production by a-emitters. There was no 

 apparent difference in the incidence and distribution of the fibrosis in the rats 

 given either single or repeated doses of ^^^Pu. 



With the a-emitting bone-seekers, tumours are frequently found in sites 

 other than the femur and tibia. In the present experiments, of the twenty 

 tumours (in 11 tumour-bearing rats) following repeated injections, twelve 

 were in the femur and tibia and three in the spine, with five in other bones. 

 Following single injections, of the twenty- five tumours (in 17 tumour- 

 bearmg rats) eleven were in the femur and tibia, seven in the spine and seven 

 in other bones. 



With regard to non-skeletal tumours there was one case of myeloid 

 leukaemia following the single injection and three cases following the repeated 

 injections. Spontaneous cases of myeloid leukaemia have not been observed 

 hitherto in our rat colony. 



EXTERNAL RADIATION EXPERIMENTS 



Experiments with localized external radiation involve fewer problems of 

 dosimetry than those with the bone-seeking isotopes, since the dose distri- 

 bution is more uniform. Figure 3 compares the mortality and bone-tumour 

 incidence for (a) a single dose of 3,000 r to one hind limb and (6) three doses of 

 1,000 r at two-weekly intervals to one hind limb. 140 kVp radiation was used 

 in both cases. 



In the single dose experiment there were a number of early deaths, but 

 of the thirty-four animals surviving six months, 12 developed bone tumours 

 between six and twenty months. In the repeated dose experiment only one 

 bone tumour developed (at seventeen months) from 15 animals surviving six 

 months. 



In this experiment a considerable difference was observed in the degree 

 of histological damage between the two groups. With a single dose of 3,000 r 

 about one-half of the bones examined showed obvious peritrabecular fibrosis, 

 especially in the early post-irradiation period, and more than three-quarters 

 showed considerable abnormality in the epiphyseal plate. With the repeated 

 3 X 1,000 r treatment there was little evidence of peri-trabecular fibrosis and 

 only about one-half of the animals showed epiphyseal plate abnormality. 



