PHOSPHORYLATING ACTIVITY OF MITOCHONDRIA AFTER TOTAL BODY IRRADIATION 



for the estimation of oxidative phosphorylation. No effect of irradiation 

 even with doses of 20,000 r has been found, which is in accordance with 

 results of Potter et aP. From this it should not be concluded that the 

 mitochondrial defect is necessarily secondary to some radiation-induced 

 aberration in other parts of the cell. For one thing, it has not been possible 

 to keep the mitochondria in vitro in a state of active metabolism for a period 

 of 2 hours, and this might well be essential for the lesion to develop, as has 

 been observed with other forms of radiation-induced damage. The results 

 obtained with rat spleen do not allow an evaluation of the radio-sensitivity 

 of the mitochondria in the various haematopoietic cells, since this organ 

 contains beside lymphoid elements, also variable quantities of erythropoietic 

 and myelopoietic cells. Our results with thymus mitochondria indicate that 

 the mitochondria of lymphoid cells are affected by total body irradiation. 

 In order to assess the sensitivity of mitochondria from erythropoietic cells in 



80 



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-^so 



o 



E 



W 



20 



J 



I 



Figure 6. Oxidative phos- 

 phorylation of spleen mitochon- 

 dria at 4 hours after various 

 doses of total body irradiation 

 of rats subjected to intermittent 

 hypoxia for a period of 3-4 

 days. Black bars : phosphate 

 uptake jmgN ; white bars : 

 oxygen uptake jmgl^i 



^ ^ ^ 





C 





f- f- 

 S ^ 



this respect, an increase of the red cell forming elements has been induced 

 by exposure of the animals to intermittent hypoxia for a period of 3 to 4 days. 

 Mitochondrial preparations from the spleens of these pretreated rats were 

 found to exhibit an increased rate of oxidative phosphorylation, with a con- 

 comitant increase of P/O ratios to nearly double the control values (Figure 5). 

 This activity is also severely depressed after total body irradiation (Figure 6), 

 which indicates that the activity of mitochondria from erythropoietic cells 

 is also susceptible to irradiation. 



INTERPRETATION 



The work so far summarized has been mainly of a descriptive kind. The 

 significance of the disturbance of oxidative phosphorylation with regard to 

 the mechanism of radiation injury to the cell is not known. Also the nature 

 of the derangement of oxidative phosphorylation is still obscure. There 

 have been suggestions that it might be secondary to the increased ATP 

 breakdown which occurs in spleen homogenates following total body 



206 



