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lar situation in which a number of compounds are irradiated simultaneously 

 must necessarily exist in the intact cell. 



Following studies on the action of radiations on simple organic com- 

 pounds, Dale (2) undertook an investigation of the action on enzyme systems 

 in vitro, and several crystalline or partially purified enzymes were shown to be 

 inactivated in dilute solution. Detailed studies of these enzyme mactivations 

 demonstrated protection against loss of catalytic activity by the addition of vari- 

 ous substances to the enzyme solutions. 



The oxidizing ability of the products of ionization of water led Dr. Bar- 

 ron to consider the possibility that the sulfhydryl enzymes would be inactivated 

 by radiation through conversion of their -SH groups to the inactive disulfide 

 forms This idea was tested with solutions of crystalline or partially purified 

 enzymes, e.g., hexokinase, succinic dehydrogenase, phosphoglyceraldehyde de- 

 hydrogenase, adenosine triphosphatase and urease, whose catalytic activity was 

 known to be dependent upon -SH groups. Inhibition of the activity of sulfhydryl 

 enzymes was generally noted, and this inhibition could be reversed, as Dr. Bar- 

 ron explained yesterday, by the addition of glutathione after medium or low doses 

 of X-rays. The results of these studies demonstrated the inherent susceptibility 

 of sulfhydryl enzymes to the action of ionizing radiations. 



Other experiments on the effects of radiation on enzyme systems 

 in vitro have been conducted, and, in some cases, inhibitory effects were noted. 

 In general, the in vitro experiments have given a good indication of the types of 

 results which can be obtained by irradiation of enzyme systems. Factors such 

 as the purity of the enzyme, the concentration of the enzyme in solution, and the 

 nature of the impurities markedly affect the amount of alteration of enzyme ac- 

 tivity. However, the increasing realization of the limitations of in vitro studies 

 of this sort has forced investigators to turn to the more difficult task of examin- 

 ing the actions of ionizing radiations on enzyme systems in vivo. 



Many investigators are now searching for disturbances in carbohydrate 

 metabolism. Although research on this phase of metabolism has not yet provid- 

 ed an acceptable explanation for radiation damage, the information obtained to 

 date represents a valuable contribution to the ultimate understanding. 



Following the in vitro studies on sulfhydryl enzymes, attention was di- 

 rected to the possible effect of radiation on these enzymes in the intact animal. 

 Recent experiments in our laboratory (3) on tissues taken from rats subjected to 

 high doses of X radiation illustrate the resistance of enzymes to inactivation 

 in vivo. When animals were sacrificed at 24 hours after 20, 000 r, there was no 

 appreciable decrease in the oxidation of several substrates by liver slices. Suc- 

 cinate, oxalacetate, citrate, a-ketoglutarate, glutamate, fumarate and malate 

 were all oxidized at a normal rate. Thus we see that in the intact animal, a 

 presumably radioresistant tissue such as liver, does not exhibit a decrease in 

 ability to oxidize several intermediates of the tricarboxylic acid cycle. Similar 

 results were obtained in the case of kidney, heart, and brain, which are also 

 considered to be radioresistant. 



One point that I should like to make is that it is important to study bio- 

 chemical mechanisms in tissues that are known to be radiosensitive. 



One cannot extrapolate results obtained on radioresistant tissues to 

 radiosensitive tissues like the spleen or the thymus. In the case of the spleen, 

 one obtains a somewhat different picture for exposures as low as 100 and 200 r 

 result in a pronounced decrease in the endogenous respiration. This is some- 



