RADIO-PROTKCrilVK ACTION Ol CIERTAIX AMINKS 



prctreatnuMit, is airordcd by llic h\ ijollicsis, that llic mechanism of radio- 

 chemical protection in vivo is partly due to relative anoxaemia, causing steeper 

 gradients in fall-oflin oxygen tension in tissues — an effect annulled by pressuri- 

 zation, and partly due to removal of oxygen and oxidizing radicals in cells due 

 to pharmacological alterations in oxidative metabolism, which follows a 

 common pattern for different protective agents and which is quantitatively 

 related to the degree of cellular toxicity induced. The results obtained by 

 Bacq et al.^^ using sodium fluoracetate (a competitive inhibitor of the enzyme 

 aconitase in llie tricarboxylic acid cycle, which causes accumulation of 

 citrate, and protects mice against irradiation), also seems best explained by 

 its effect on oxidative metabolism, rather than by competition for free radicals 

 by citrate. 



ADDENDUM 



Since the above experiments were conducted, our attention was drawn to 

 an internal report of Salerno et al.'^'^ in which oxygen respired at 5 atmospheres 

 absolute pressure (60 lb per sq. in.) completely reversed the protective action 

 of cysteamine (100 mg/kg) in rats irradiated with 820 r X-rays. We have 

 extended our experiments to cover this degree of pressurization with oxygen, 

 but a residual protection results for the disulphide cystamine (-S-S) at 

 60 \h. per sq. in., which is practically the same as for 45 lb. per sq. in., in 

 agreement with the trend of the curve shown in Figure 4. 



The addition of cyanide pretreatment to pressurization with oxygen, 

 results in a much more substantial reduction in the protection of cystamine 

 (and 5-hydroxytryptamine) but a residual protection exists, even at 60 lb. 

 per sq. in. pressure. The full results of these experiments will be published 

 shortly. 



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