89 



may be complicated by rapid removal of some pyknotic cells. This is particular- 

 ly evident in the blood stream, as shown by Trowell (4). 



BARRON: How many hours after irradiation can you get lymphopenia? 



PATT: Within a few hours after irradiation. Maximal spleen involution 

 or involution of lymph nodes occurs within a day or two after 100 r to the whole body. 



DUBOIS: The endogenous respiration of either the spleenor thymus gland 

 decreases markedly in one day after exposures to 400 r. It may decrease a little 

 more in the following 3 to 5 days. There is then a gradual return so that at 1 4 and Zl 

 days the rate of endogenous respiration again approaches the normal value. This is 

 a reversible inhibition of endogenous respiration and correlates quite well in time 

 with the reversibility of the functional activity of these tissues after 400 r. 



BARRON: You have not measured the respiration in terms of DNA? 



DUBOIS: No. 



PATT: The curve for endogenous respiration resembles very nicely 

 the curve for spleen involution. With 400 r, the peak would appear at about 3 

 days, with recovery becoming apparent during the next several days. 



DUBOIS: In connection with these ob- 

 servations on the respiration of tissues of 

 irradiated animals, I feel that it is not prof- 

 itable to study the oxidative phase of carbo- 

 hydrate metabolism in the liver, kidney, 

 heart, and brain, but that there is a great 

 deal to do in connection with radiosensitive 

 tissues like spleen and thymus. Studies of 

 ' the overall metabolic activity of tissue 

 slices may be considered as preliminary to 

 more definitive experiments. 



12 Z? W" 



HOURS AFTER 800 R OF X-RAY 



Figure 1. Effect of 800 r of X radiation on 

 the accumulation of citric acid in tissues of 

 fluoroacetate-treated rats. (This chart 

 was published in a paper by K.P.DuBois, 

 K.W. Cochranand J. DouU in Proc. Soc. 

 Exp. Biol, and Med. 76, 422-427 1951). 



To obtain further information on the 

 gross effects of irradiation on the oxidative 

 phase of carbohydrate metabolism, we 

 have used the sequential blocking technique 

 developed byPotter (5), in which fluoroace- 

 tate is employed to inhibit citric acid oxida- 

 tion in tissues . This method of studying 

 the actions of poisons on carbohydrate metabolism consists of giving fluoroacetate 

 to irradiated animals at various times after exposure and sacrificing the animals for 

 citric acid measurements. If radiation were interfering with the formation of citric 

 acid at some point in the cycle, it would be revealed here by an increase or decrease in 

 the amount of citric acid accumulated in the tissues relative to the controls. 



The use of fluoroacetate technique (6) showed that there is no effect on 

 citric acid formation in heart or brain after 800 r. There was a small inhibitory 

 effect in the kidney; this could not be obtained with sublethal doses and, there- 

 fore, was not considered to be of any appreciable significance. There was a 

 marked inhibition of citric acid formation in the spleen and the thymus. This indi- 

 cated that some step that ultimately leads to citric acid formation in these organs is 

 inhibited by whole-body X irradiation. After the administration of a lethal dose 

 to rats, the effect was irreversible. The results of these experiments are illus- 

 trated in Figure 1 . 



