SULPHYDRYL PROTECTION AGAINST MAMMALIAN RADIATION INJURY 



the first 30 to 60 minutes after irradiationii. A brief period of chilling at 

 2°C immediately after X-ray exposure completely reverses the effect. 

 Temperature dependence of cysteine action before irradiation has also been 

 shown. The latter may be thought of perhaps in terms of a decreased rate 

 of reaction with oxygen in the cold. An explanation of the post-irradiation 

 temperature dependence for cysteine protection of thymus lymphocytes is 

 not readily apparent, but it is clear that we must also inquire about the role 

 of delayed and of chain reactions in the interpretation of these phenomena. 

 The pathways for reaction or degradation of organic radicals formed during 

 irradiation may depend upon oxygen availability in addition to other factors 

 such as pH, temperature and the redox potential". It is possible that 

 decreased oxidation of cysteine during a critical post-irradiation period 

 frees oxygen for reaction with chemical intermediates which might other- 

 wise be directed into other channels. The results with thymocytes may be 

 contrasted with chemical protective effects in bacteria. Several modes of 

 action apparently prevail in the protection of the various systems, owing 

 perhaps to differences in the nature of the chemical intermediates and their 

 reactions, the time required for development of irreversible injury, and the 

 relative contribution of the intra- and extra-cellular phases to the over- 

 all effect. 



Uniformity of the protection (dose reduction) by cysteine against a number 

 of radiation sequelae in the intact animal suggests that the decisive action 

 occurs at an early stage in the chain of events. It does not necessarily imply 

 protection against all radiation changes since different primary mechanisms 

 may be involved in their development. It should be emphasized that there 

 is scant information concerning protection against the more chronic sequelae 

 of irradiation, although one might suppose a priori that some effectiveness 

 would also be manifest here. For the present, these modifying effects may 

 be interpreted best in terms of the more immediate physicochemical ramifi- 

 cations of energy transfer. Protective chemicals of this sort may alter the 

 effective radical concentration {e.g. of OH or HOg) either directly or 

 indirectly by relative depletion of oxygen. Effects on chain reactions 

 initiated by the primary interactions may also be involved. The experi- 

 mental findings in general are consistent with such assumptions and there 

 is little basis at the moment for postulating a more selective in vivo protection 

 of one or another biochemical entity or physiological mechanism by this 

 class of chemicals. 



Reference has been made from time to time to the possibility of a primary 

 attack of ionizing radiation on sulphydryl groups generally 2^. More 

 recently, it has been suggested that inactivation of Coenzyme A may be of 

 importance in the initiation of cellular damage by irradiation 2^. There is 

 now ample evidence that sulphydryl enzyme inactivation is neither a selec- 

 tive nor a uniform process in vivo^- 1". The possibility that effects of this 

 sort may occur in areas where — SH groups are few and their inactivation is 

 critical cannot be ruled out, however. It should be noted that there is no 

 evidence for an over-all destruction of Coenzyme A by whole body X- 

 irradiation. As shown by Thomson and Mikuta^s, rats given^ lOOOr 

 retain their capacity to acetylate p-aminobenzoic acid and sulphanilamide 

 for at least 3 days after exposure. While it is true that CoA levels in the 



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