78 D. W. VAN Bekkum 



identification of the disturbance of DNA synthesis with the 

 primary biochemical lesion. Since synthetic processes in the 

 nucleus are generally considered to be dependent on energy- 

 generating reactions which occur in the cytoplasm, it was 

 thought possible that the disturbance of nuclear functions 

 which occurs after irradiation might be the result of damage 

 to biochemical reaction systems outside the nucleus. The 

 cytoplasmic reaction chains by which energy is produced in a 

 transportable form, e.g. ATP, are chiefly anaerobic glycolysis 

 and the oxidations performed by way of the citric acid cycle. 

 In terms of the production of high energy phosphate bonds, 

 the latter are by far the most important. 



The oxidative phosphorylations occur in the mitochondria 

 and these cytoplasmic structures have received relatively 

 little attention from radiobiologists. The older literature con- 

 tains some reports on morphological changes in mitochondria 

 which were observed shortly after irradiation of plant and 

 animal cells (Nadson and Rochlin, 1934; Hirsch, 1931; 

 Colwell, 1935). The changes described are presumably non- 

 specific but this applies to most of the radiation-induced 

 nuclear changes as well. Several of the authors claim that 

 the mitochondrial effects precede the morphological changes 

 which occur in the nuclei. On the other hand, Trowell (1952) 

 in a recent investigation of the effect of radiation on lympho- 

 cytes has reported only minor changes of the mitochondria. 



In 1952 studies were initiated in this laboratory with the 

 object of collecting information on the effects of ionizing 

 radiation on the oxidative phosphorylations. In preliminary 

 experiments with mitochondria from various tissues, a 

 decreased phosphorylation was observed in rat spleen mito- 

 chondria after total body irradiation (van Bekkum et al., 1953). 

 Most of our subsequent work has been carried out with rat 

 spleen mitochondria but this effect has also been demon- 

 strated in mitochondria from mouse spleen and rat thymus. 

 A depression of oxidative phosphorylation in rat spleen 

 mitochondria after total body X-irradiation has also been 

 described by Potter and Bethel (1952) but their paper does not 



