19 



RADIO-PROTECTIVE ACTION OF 

 5-HYDROXYTRYPTAMINE 



H. A. S. VAN DEN BrENK 



Radiobiological Research Unit, Cancer Institute Board, 



Melbourne 



Many chemicals are known, which protect animals against ionizing radi- 

 ations^. However, their exact mode of action remains in doubt. By analogy 

 with polymer experiments in vitro, the mechanism appears dependent on an 

 indirect competition for oxidizing radicals, particularly HOg radicals, 

 produced by irradiation in tissue fluids'-. Other evidence is advanced to 

 support this hypothesis. Protective action in vivo, is substantial only for 

 radiations giving low ion densities along the track of the ionizing particles; 

 for Escherichia coli, chemical protectors are active in the presence of anaero- 

 biosis^. Alexander et al^ also state that whilst many chemical protectors, 

 efficient in vivo, are vasoconstrictors, e.g. certain catechol amines and pitressin, 

 and possibly give protection as a result of induced tissue anoxia, this factor 

 does not apply to certain other protective substances. 



More recently, Bacq^ has been more impressed with the views of L. H. Gray 

 and others^, stressing the importance of cellular anoxia, induced by radio- 

 protective chemicals, and has added evidence in support. However, Bacq 

 remains convinced that an eclectic theory of cellular anoxia does not suffice, 

 as an explanation of all aspects of radio-protection, and feels that some 

 fundamental physico-chemical action must be accepted, based on the idea of 

 competition for free radicals^ or perhaps that of a radio-resistant protector- 

 enzyme complex, which is subsequently dissociated by irradiation, with 

 restoration of normal activity*'' "^ . The protective action in vivo of a non-SH 

 substance such as tryptamine, is particularly stressed by Bacq, as not suitably 

 explained by the last hypothesis, or by the anoxic theory. 



In reviewing these deliberations and others, concerning radio-protective 

 action in vivo, certain conclusions seem inevitable: 



(?) intracellular and intercellular organization is such that complex con- 

 centi'ation gradients of protective metabolites and pharmacological substances 

 exist, which seem to preclude a close analogy with protection of simple 

 chemical systems in vitro 



(ii) for a chemical or metabolite to manifest substantial protection in vivo, 

 toxic side effects invariably accompany this action. For ' less toxic ' substances 

 such as cysteine, compared on a molar basis with more toxic substances such 

 as cysteamine, to achieve comparable radio-protective action in vivo, the dose 

 must be increased, and results in comparable toxicity 



(Hi) the fundamental mechanisms which govern 'selective toxicity' of 

 chemical agents on living matter, would seem cogent in relation to the effects 

 of ionizing radiations. 



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