STRONTIUM-90 AND CARCINOGENESIS IN RATS 141 



Among the delayed effects of ionizing radiations on mammals the induc- 

 tion of leukaemia is well recognized. While the precise processes leading to 

 leukaemogenesis are still not clear, we may recognize two components in the 

 action of ionizing radiations at the cellular level; the probability of tumour 

 induction and a cytotoxic effect. The latter effect may be mediated by 

 primary injury intrinsic to the cell or by extrinsic factors such as the impair- 

 ment of ceU nutrition. The production of a neoplasm may then be regarded 

 as a balance between these two components. There are indications that the 

 probability of induction of leukaemia is dose-dependent, to a limit which is 

 determined by the preponderance of cytotoxic effect. In other words the 

 chances of inducmg leukaemia depend upon the extent of injury to the 

 haematopoietic system and the percentage of such altered cells surviving and 

 capable of multiplication. It would appear from the data that such a situation 

 does exist, inasmuch as the incidence of leukaemia per rat week of observation 

 shows a 2-5 times increase between groups B and C. In both these groujDS the 

 histological study of cytotoxic effect on the bone-marrow indicated only mild 

 or moderate effects. However, in group D the bone-marrow was completely 

 atrophic, suggesting a profound cytotoxic effect with hardly any haemato- 

 poietic cells capable of survival or multiplication to cause the appearance of 

 leukaemia. 



In contrast to the induction of leukaemia the incidence of osteogeneic 

 sarcoma shows some interesting variations. This may be explained by com- 

 paring the relative radiation sensitivity of the osteoblasts and the cells of the 

 haematopoietic system. It is well recognized that the osteoblasts are relatively 

 less radiosensitive than the cells of the blood-forming organs. Table II shows 

 that the lowest level of skeletal burden of ^°Sr to cause osteogenic sarcoma is 

 in group C. In group D the incidence rate is increased by about 2-7 times. 

 This indicates that the minimum dose to cause osteogenic sarcoma is different 

 from that required for leukaemogenesis and the limiting dose for the osteo- 

 genic sarcoma is not attained even in animals with as high a skeletal burden of 

 33 [ic of ^^Sr. This presumably suggests that those cell types which are less 

 radiosensitive require a higher dose for the induction of neoplastic change and 

 the limiting dose is significantly increased, since the latter is determined by 

 the dose which has the highest cytotoxic effect on the particular cell system 

 under consideration. 



By comparing the incidence rate of leukaemia and osteogenic sarcoma in 

 groups B, C and D, there is an indication that at low levels of skeletal burden 

 of ^°Sr, the primary delayed somatic effect would be leukaemia, at intermediate 

 levels both leukaemia and osteogenic sarcoma and at high levels only 

 osteogenic sarcoma provided the animals survive a sufficient length of time 

 before pancytopenia or other causes of death supervene. It is however 

 necessary to exercise caution in regard to these observations, since the number 



