RADIATION-INDUCED BONE TUMOURS 155 



6 X 500 r experiment, of peri-trabecular fibrosis and only a slight incidence 

 of obvious plate abnormality. 



The different quality of radiation in these two latter experiments could 

 considerably affect the pattern of radiation dose distribution in the bone so 

 that, apart from the small numbers of animals used and the consequent 

 large statistical errors, it is difficult to draw conclusions from these data 

 about the effect of fractionation. 



However, in the results of Figs. 3 or in the comparisons of Figs. 3 and 4 there 

 is no evidence that, under the conditions of these experiments, fractionation of 

 the dose increased the tumour incidence. The present evidence suggests, in 

 fact, a decrease. 



DISCUSSION 



With ^^P there is clear evidence of an increase in bone-tumour incidence 

 and shortening of tumour development time with fractionation of the dose. 

 With 2^^Pu no very marked difference was observed, though there was some 

 indication of earlier development of tumours with fractionation. With 

 localized external radiation to the hind limb there was certainly no increase in 

 tumour incidence with fractionation, but possibly a decrease. 



These experiments do not therefore establish any common pattern of 

 response which could be used to elucidate mechanisms. In the case of ^^P it 

 must be recognized that the radiation dosage pattern within the bone is 

 complex and one or more of a number of factors might be involved in the 

 difference of response between single and fractionated treatments. 



The suggestion that the greater tumour incidence with the ^^P fractiona- 

 tion treatment was because fractionation permitted a gi'eater survival of 

 potentially malignant cells does not appear to be supported by the X-ray 

 results. However, the dose of 1,000 r used m the X-ray fractionation experi- 

 ments will produce much cell death and it would be of great interest to study 

 bone-tumour production with external radiation using a larger number of 

 smaller fractions. 



With 239p^ ^}^Q effect of fractionation of treatment on cell survival would 

 be expected to be less than with low LET radiation because of the severe 

 damage caused by the passage of a single a-particle through a cell. 



Another possible explanation for the high carcinogenic efficiency of 

 repeated ^^^P treatments and of ^^^Fu, both single and repeated, is that the 

 radiation exposure is protracted enough to involve the irradiation of regenera- 

 ting tissue. In the fractionated treatment with external radiation (3x1 ,000 r) 

 the interval between first and last treatments may not have been sufficiently 

 long. It is possible that the high incidence of bone tumours at 6 x 500 r is 

 the result of a lengthened period of exposure. Again, external radiation studies 



