94 



Figure 2 shows the effect of radiation on citric acid formation in the liver. Al- 

 though one does not observe any effects of radiation on the ability of liver slices 

 to oxidize a number of different substrates, the fluoroacetate technique indicates 

 that there is a disturbance in citrate formation in this organ. Although we do not 

 know the exact cause of this biochemical change, we suspect that a factor that 

 normally regulates citrate formation in the liver of the male rat is altered or 

 destroyed by radiation. 



This change in the metabolism of the liver is not associated with the 

 lethal action of radiation because the effect is irreversible after 400 r in con- 

 trast to the reversible effect on citrate synthesis in the spleen and the thymus. 

 The effect on the liver persists for at least 3 months after 400 r. 



KAPLAN: What happens to the female? 



DUBOIS: The values in the female are about normal after irradiation. 

 There is quite a wide normal range, but both normial and irradiated female ani- 

 mals accumulate large quantities of citrate in the liver after fluoroacetate treat- 

 ment. 



PATT: Does citrate accumulate in the male castrate? 



DUBOIS: Yes, without radiation. We suspect that it might be due 

 either to interference with or the prevention of synthesis of androgenic com- 

 pounds and/or adrenal cortical hormones. We have done a considerable amount 

 of work along this line, which indicates that castration will produce an effect like 

 radiation and that treatment of female animals with testosterone will decrease 

 citrate formation to the level seen in the male. 



CARTER: Could this not also be due to the failure of the liver to inac- 

 tivate the estrogenic hormone after irradiation? 



DUBOIS: Yes, that is possible. 



CARTER: This is commonly seen in liver disease. 



DUBOIS: Estrogens do not have any stinnulatory effect in normal ani- 

 mals. If one gives estradiol to normal male animals, citrate formation does not 

 increase appreciably. 



CARTER: That may be due to the normal livers' capacity for inactiva- 

 tion. 



DUBOIS: Our experiments with adrenal and sex hormones are in line 

 with the idea that there is a hormone involvement in the radiation effect on cit- 

 rate formation. However, the experiments do not prove it. 



KAPLAN: This is just after irradiation of the liver? 



DUBOIS: The effect is not detectable immediately after irradiation but 

 rather requires several hours to become pronounced. The nitrogen mustards 

 will produce, (7) qualitatively and quantitatively in most respects, the same type 

 of response as radiation on citric acid formation as shown in Table I. Citrate 

 formation in the spleen and thymus is markedly depressed by doses of methylbis 

 (p-chloroethyl) amine in the LD50 range, and the amount of citrate formed in the 

 liver is markedly increased just as it is in irradiated male rats. 



