20 



EFFECTS OF RESPIRED 

 OXYGEN— RADIO-PROTECTIVE ACTION OF 

 CERTAIN AMINES— (a) LETHALITY STUDIES 



H. A. S. VAN DEN Brenk and Ruth Moore 



Radiobiological Research Unit, Cancer Institute Board, 



Melbourne 



Considerable experimental evidence has been obtained associating chemical 

 protection against ionizing radiations with alteration in oxygen tension. 

 Particular attention has been given to sulphur-containing protective agents 

 which exist as reducing (-SH) and oxidizing (-SS-) entities. Loiseleur and 

 Latarjet^ reported that cysteine, ascorbic acid and aldehydes increased the 

 yield of H.^Oo in X-irradiated water, the reducing agents being considered to 

 act as hydrogen donors, hydrogen peroxide being formed from combination 

 with HO2 radicals as a detoxication product. Using the Hersch cell for 

 oxygen assay, Gray^ has demonstrated the consumption of oxygen by 

 cysteamine in vitro; Pihl and Eldjarn^ have correlated the degree of protective 

 action with the ability to form mixed disulphides. Fischer* showed that 

 cysteamine, like anoxia, causes accumulation of organic acids (particularly 

 pyruvic and lactic acids) in the plasma. 



Injections of cysteamine, cysteine or glutathione cause marked falls of 

 oxidation-reduction potentials in muscle and tumours^. Scott^ has reported 

 that pure oxygen at 1 or 2 atmospheres protects mice against lethal doses of 

 cysteamine, whilst mice given sub-lethal doses of cysteamine, show diminished 

 tolerance to anoxia. Bacq et al. "^ reported that cystamine decreases the oxygen 

 saturation of venous blood, in rats, although histamine fails to do so. 



The effects of reduced oxygen tensions on the radio-protective action of 

 certain substances in vitro and in vivo have been studied for some time. Whilst 

 10 per cent oxygen does not protect mice against X-rays an additive effect 

 obtains if combined with cysteine^. Similar results were obtained for moderate 

 hypoxia in mice with cysteamine and cystamine^. 



However, Devik^" has reported that cysteamine fails to give significant 

 protection for local tissue damage due to radiation, in perfused rabbit ears 

 rendered severely anoxic. 



One would expect the effectiveness of protective agents in the presence of 

 raised oxygen tensions to be substantially decreased if the protective pheno- 

 menon depends on some physical interference with access of oxygen to the 

 site of radiation damage within the cell as distinct from interaction with free 

 radicals. Similarly, if the protective agent causes increased oxygen con- 

 sumption by the tissue and local depletion of oxygen, provision of freely 



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