158 BENSTED, BLACKETT, COURTENAY, AND LAMEETON 



tritiated thj-midine wliich shows it's not a simple problem. There are some cells which 

 definitely crawl up the trabeculae as the plate retreats and these may receive nearly the 

 whole dose from repeated injections. 



berenblum: In the case of the repeated dose experiments with ^^p what was the interval 

 between the three doses? 



lamerton: The interval between doses was two weeks so that the animals given these 

 doses were subjected to irradiation for at least four weeks longer than those given a smgle 

 dose. 



berenblum: Well, what I had in mind was, supposing that the length of tune necessary 

 before you got your irreversible change was, for the sake of argument, twelve weeks, 

 after ^^'hich time the carcinogenic process was more or less committed, then in that case a 

 period of four weeks would be quite a signiflcant proportion of the twelve weeks. I don't 

 know whether that might or might not influence your mterpretation. 

 LAMERTON: One would have expected to have obtained a similar difference with repeated 

 doses of X-rays if such a mechanism were operative. 



cottier: Speaking of bone tumours induced by ionizing radiation, I should like to draw 

 your attention to the possible importance of some endocrine factors. In our stram of mice 

 we observed after whole-body irradiation, at the age of 3 months with 450 to 600 r, 

 osteogenic sarcomas only in females and the important thing was that this strain also 

 developed a high percentage of ovarian tumours after the irradiation. They also developed 

 an ossification of the bone-marrow space, internal hyperostosis and only in such cases 

 did we find osteogenic sarcomas in a significantly different percentage, that is 9 m the 

 females and none m the males. Now I should like to ask if anybody working with bone 

 tumours has observed sex differences such as this? 



lamerton: Our o^vn work has been primarily with males but there were some observa- 

 tions of Pybus and Miller some time ago when their Newcastle strain of mice suddenly 

 developed a high spontaneous incidence of bone tumours. These began to appear at about 

 6 months of age and if I remember rightly, the incidence hi females was something like 

 65% and in males about 25%. So in this case spontaneous bone tumours showed a 

 considerable sex difference. Miriam Finkel has worked both with male and female 

 animals, I beheve, in her experiments with the bone-seeking isotopes but she has not 

 found any considerable difference between them as far as I know. 



ALEXANDER: My comment is really rather similar to Dr. Cottier's. I wondered whether 

 the difference between ^2? and ^"Sr couldn't be due to an abscopal effect? With ^^^p the 

 whole-body will be hradiated and if, in fact, you give fractionated doses you are givmg 

 contmuous whole-body radiation. If contmuous whole-body irradiation is producmg a 

 continual hormonal stimulus this might then result in the much higher mcidence of 

 tumours. Whereas with ^"Sr the fractionation would not give you a uniform whole-body 

 irradiation and you wouldn't get this continual stimulation even by fractionating it. 

 lamerton: You would get some degree of whole-body irradiation in a mouse with ^"Sr 

 because a mouse is smaU. 



mole: I only want to comment on Dr. Cottier's comment. Wliat seems to me to be unusual 

 is the occurrence of osteogenic sarcoma. I think everybody has probably observed a high 

 incidence of ovarian tumours as weU as internal hyperostosis in various strains of mice 

 given single doses of radiation but I think that tais is the only report I know of with a 

 reasonable incidence of osteogenic sarcoma in animals given a single dose of external 

 radiation. 



zeleny: Do you have any estimate of the absorbed radiation dose in yoiu- plutonium 

 experiments and could you compare it with the ^^P dose? 



