798 ADVENTURES IN RADIOISOTOPE RESEARCH 



If irradiation blocks the incorporation of acetate carbon into fatty 

 acids or cholesterol, more i*C may take its way through other metabolic 

 pathways. Such an interference will lead to an increased i*C level of the 

 CO2 of body fluids, the result of this increase being, for example, an 

 enhanced ^^C incorporation in liver or muscle glycogen. A decrease in the 

 amount of ^^C trapped in metabolic pools of Krebs' cycle due to irradia- 

 tion lesions will act in the same way. This increase in the ^^C content of 

 glycogen may not be due to a larger glycogen production, but to a lowered 

 sensitivity of i*C as an indicator. A radiation lesion produced in the liver 

 may thus be responsible for an enhanced i^C incorporation into a muscle 

 fraction. 



In a similar way, interference with the conversion of acetate into 

 acetoacetate in the liver will interfere with the i*C incorporation into 

 muscle fractions, most of the muscle acetoacetate being presumably 

 carried into that tissue from the liver. In this case, we interfere not only 

 with the sensisitvity of the indicator of processes taking place in the 

 muscle, but even with the turnover rate. 



The injected labelled acetate is diluted with endogenous acetate 

 formed by catabolism of fatty acids and other compounds. If irradiation 

 interferes with the catabolic processes or with the rate of interchange 

 between intra- and extra hepatic fatty acids, but does not influence, or 

 influences to a minor extent only the incorporation of acetate into fatty 

 acids, the activity level of body acetate will be increased and we observe 

 an increased i^C incorporation in fatty acid fraction or protein samples, 

 for example, which is due not to an increased turnover rate, but to a 

 decrease in the sensitivity of the indicator. More ^^C is incorporated with 

 the tissue fraction, but the amount of I'^C renewed may be practically 

 the same, and vice versa. 



While a change in the sensitivity of the radioactive indicator may be 

 responsible for the change in the ^*C uptake observed, this is far from 

 always the case. Irradiation may divert i'*C present in intermediary 

 compounds of acetate metabolism from oxidation via the Krebs cycle. 

 Such diversions were repeatedly observed, for example, in experiments 

 with liver slices^^^ Addition of pyruvate, citrate, a-ketoglutarate or 

 malonate was found to diminish the output of ^"^OOa, while an increased 

 incorporation of ^^C into a-ketoglutarate and other compounds w^as 

 found to take place. Furthermore Altman et alM\ when investigating 

 marrow homogenates of irradiated and of control rabbits incubated in 

 the presence of a- ^*C- acetate found a markedly increased incorporation 



^1^ A. B. Pardee, C. Heidelberger and V. R. Potter, J. Biol. Chem. 186, 

 625 (1950). 



^-' K. I. Altman, J. E. Richmond and K. Salomon, Biochem. et Biophys. 

 Acta 7, 4G0 (1950). 



