MODIFICATION OF LATE EFFECTS OF IONIZING RADIATION 305 



a life-span shortening reduction, whereas I think other people, giving doses under more 

 strict conditions, find that bone-marrow provides very little protection, so that would 

 seem to indicate that the linear dose-response curve might not be equitable. 

 UPTON: Yes, I'm not really sure in my own mind that bone-marrow has any effect 

 outside the haemopoietic system. Again, tliis implies that you can take a mouse and 

 carve it into pieces and look just at the haemopoietic system and forget about every- 

 thing else. 



ALEXANDER: I thought there were actual experimental data showing tliat with dose 

 regimes which didn't produce acute deaths then bone-marrow therapy didn't help a great 

 deal in Ufe-span shortening. 



UPTON: No, I tliink that this will depend a lot on the extent to which the animal is prone 

 to leukaemia induction because it's well established now that bone-marrow does afford a 

 substantia] protection against leukaemia induction and in a strain in which leukaemia is 

 an important lethal event following radiation then shielding bone-marrow, or bone- 

 marrow infusion would be expected to reduce the life-shortening effectiveness of radia- 

 tion. 



BACQ: Someone in Liege has done a good deal of work on protection and I know that 

 Dr. HoUaender doesn't like it very much, but he has tried to overcome this difficulty 

 of having no unprotected controls by giving two irradiations at weekly intervals so as 

 to increase tlie numbers of leukaemias in the controls. He has also used a very elaborate 

 tjrpe of statistical treatment for his results. He has tried several doses, and he came to 

 the conclusion that cj^steamine in doses wliich are quite effective in reducing acute 

 lethality do not decrease, in a statistically significant way, the incidence of leukaemia. 

 UPTON: I think mention has been made of protection of lens against cataract induction. 

 We have tried very hard to protect the mouse with AET and we have been able to get no 

 protection whatsoever. We haven't studied the uptake of labelled AET in the lens and, 

 conceivably, we just don't get enough AET across the aqueous humour into the lens, 

 but I suspect that one should be on guard against tissue variations and drug variations 

 in the extent to which one can expect protection. 



BACQ: The best way to do this is not to give the protector intravenously but to give it 

 locally to the eye; in this way you can probably get a much higher amount of the pro- 

 tector within the lens. The second comment I would like to make on Dr. Scott's intro- 

 duction about the work of Harman on the increase of life-span simply by feeding the 

 animal constantly witli cysteine, 1%, I believe in the food, is that the great objection to 

 this type of study is that he has not measured the food intake of the animal, and it is 

 quite likely that the addition of 1% cysteine to the food may make it so much less 

 palatable that the animal eats much less. 



rotblat: You asked whether there is any evidence about hypocaloric feeding of mice. 

 We haven't got any but Dr. Lindop and a colleague are doing a study of the acute 

 effects. We have got no data on the long-term effects but it would appear that it 

 doesn't protect at aU, on the contrary the LD50 goes down. The question of anoxia; we 

 have done various experiments with mice breathing pure nitrogen for about 25 seconds, 

 and then given a very brief pulse of radiation. We measured the LD5o(40), the acute 

 effects and the long-term effects. What one has to bear in mind is that here too there is 

 an age factor; the protection which you get varies with age, and we believe now that tltis 

 is due to the fact that the older the animal the longer it will take to reduce the oxygen in 

 its tissues to the same level, and therefore for older animals you probably need a longer 

 time. For example, with 4-week-old animals we get a protection factor of 2-8 zL 0'2, 

 which is about the maximum because if you go to 40 seconds you don't get any change. 

 But now, if you are going to consider the long-term protection, this wiU of course again 



