93 



JONES: I wish to add a comment upon differences in the apparent 

 nature of the post-irradiation response that depend upon the time selected a 



as being a decrease in spleen size, in cell division rate, and in DNA turnover, 

 careful examination by Dr. Lola Kelly has shown that immediately after irradia- 

 tion, there is a period in which DNA turnover is enhanced. Perhaps in this case 

 there is not a genuine transitory increase in mitotic activity; the effect noted 

 may be due to the stimulation of cells that are already relatively insensitive to 

 radiation inhibition because they are in the throes of mitosis. 



In some contrast, there is another system, that of lipid metabolism. 

 Alteration of serum lipoprotein is an indicator of severe radiation damage. But 

 it is essentially an all-or-nothing type of response, whereas the post-irradiation 

 decrease in cell division and DNA turnover is a continuously graded response 

 dependent upon dosage. 



Rabbits that die from irradiation show alteration of serum lipoprotein 

 metabolism. At the same exposure, rabbits that survive do not show the change. 

 The typical response is an elevation of the higher molecular weight classes of 

 B-lipoprotein associated with a lack of removal of neutral fat from these lipo- 

 proteins. Thus, the general statement of the effect of irradiation upon lipid 

 metabolism is that lipoprotein utilization is halted by irradiation. Nevertheless, 

 such animals, examined immediately after irradiation, show a 16-fold enhance- 

 ment of lipoprotein utilization for about 5 to 10 minutes. It is after this that the 

 48-hour period of lack of lipoprotein utilization ensues. On the third day after 

 irradiation, the system again reverts to a 16- to 20-fold enhancement of the 

 normal functional level of lipoprotein interconversion and utilization of their 

 neutral fat content. 



CARTER: By lipoprotein interconversion you are referring to the shift 

 in the ultracentrifuge peaks. 



JONES: Yes, essentially it is the shift in the flotation rate with a low- 

 ering of the Sf number which accompanies the decrease in density brought about 

 by the removal of neutral fat from the lipoproteins. Starting with lipoproteins 

 that may be of chylomicron size, which have a flotation rating of Sf 40, 000, there 

 is a progressive reduction approaching Sf 6 by enzymatic hydrolysis of neutral 

 fat. 



POTTER: All in plasma? 



JONES: Yes, the whole process seems to take place in the plasma. I 

 must apologize for this discussion which deviates from the specific topic but I 

 suppose that the circulatory system or the whole mammal can be considered a 

 cellular unit. 



DUBOIS: Returning to the subject of the influence of radiation on cit- 

 rate synthesis, I would like to mention some effects that we have observed in 

 studies on the liver. Following irradiation, the liver of the male rat acquires 

 the capacity to accumulate large quantities of citric acid after fluoroacetate 

 treatment whereas, that of the normal male rat is unable to do so. However, 

 the normal fennale rat can accumulate citric acid after fluoroacetate treatment. 

 The effect of radiation here is essentially to change the metabolism with respect 

 to the response to fluoroacetate so that the liver of the irradiated male rat re- 

 sembles that of the normal female rat in its ability to accumulate citric acid. 



