306 O. C. A. SCOTT 



vary with age for the same reason, but we find in all cases that the protection against 

 life-shortening is less than for the acute effects. We get a factor of 2-8 at 4 weeks for the 

 acute effects, we only get about 1-8 to 2 for the long-term effects. 



BERENBLUM: I just have one comment about the caloric restriction effect. About 20 

 years ago Tamienbaum in Chicago did an extensive series of experiments on the effect of 

 caloric restriction and studied aU systems of tumours both spontaneous and induced. He 

 found, I beheve without exception, that the tumour induction was reduced by at least 

 50% for spontaneous mammary and lung tumours, and I think also for spontaneous 

 hepatomas and a whole series of chemically induced tumours. But since there was no 

 exception with either spontaneous or chemically induced tumours, I would say that, 

 argumg from this results, that there would almost certainly be a very significant 

 reduction in carcinogenesis by a degree of caloric restriction which not only mamtains 

 healthy life but actually extends the life-span. 



UPTON: Commg back to the question of organ differences, repeatedly in the course of this 

 meeting the mter-relation between the thymus and the bone-marrow has come under 

 discussion. It may be noteworthy that AET, at least, seems to afford very little protection 

 to antibody-forming cells, either as measured by the production of circulating antibody 

 or as measured by the abihty of such cells to produce a transplantation reaction, so, 

 this may be an important point in connection with leukaemogenesis. 

 casaeett: In regard to experiments with restricted caloric intake it is weU to remember 

 that in Mackay's classical experiments on non-irradiated rats one of the chief killing 

 diseases that was eUminated by caloric restriction was pneumonia. Sexton reported this 

 in a separate paper on the pathology of these animals and from our investigations of the 

 pathogenesis of pneumonia m that strain and in our o\\n.\ strain, it was clear that starting 

 at about 18 months in the rat there is an increasing incidence of over-growth of lymphatic 

 tissue into bronchioles causing obstruction with the production of emphysema and then 

 a high incidence of killing penumonia. Caloric restriction prevents this over-growth of 

 lymphatic tissue, emphysema and the high incidence of pneumonia so it's possible that 

 in some species this restrictive caloric feeding does not have a generalized, so much as a 

 specific, effect on certain killing diseases. The effect of radiation might therefore be 

 based on something more specific. 



UPTON: In liis summary Dr. Scott mentioned the pertinent question of split-dose studies 

 and I think tliis points up an important approach in methodology. Some years ago Heniry 

 Kaplan studied the incidence of lymphomas and thymic lymphoid tumours in C57BL 

 mice, given whole-body radiation early in life, at about 33 to 35 daj's of age. He gave 

 different total doses, and I have shown the results for just one dose-level, as I recall it 

 about 570 r. If he gave the 470 r in one treatment then he got a final incidence of thymic 

 lymphomas of about 40%. If he gave the same dose in four fractions, each one separated 

 by 1 day, the l3Tnphoma incidence was not significantly different. If given over 2 days, he 

 got a reduction in yield; over 4 days he got a higher yield of lymphomas; significantly 

 higher with 8 days and finally, with a 16-day interval between fractions, the yield 

 dropped way down. ComjDarable results were observed for higher total doses, but with 

 liigher dose levels it was impossible to give the animal the total dose in one treatment. 

 But the interval effects were observed. From this he inferred that there was a very 

 complex relationship between total dose, number of fractions, dose per fraction and 

 duration of interval. If; for example, one were doing an experiment on tumorigenesis 

 and had to contend with this kind of comphcation, without the necessary controls one 

 might be badly misled by the end result. For example, if you chose a 2-day interval 

 between doses and your protective agent enabled the animals to repair the injury more 

 rapidly so that the interval was actually more like 1 day, then a higher mcidence would 



