SULPHYDRYL PROTECTION AGAINST MAMMALIAN RADIATION INJURY 



For the sake of completeness it should be noted that there is another 

 category of modifying factor, one that is concerned apparently with the 

 events responsible for injury to specific physiological systems or to recovery 

 from such injury. Tissue shielding and transplants, pretreatments with 

 phenylhydrazine, foreign protein, oestrogens and other hormones are 

 examples of these rather specific procedures. 



There is reason to believe that protection by suitable sulphydryl sub- 

 stances, e.g. cysteine, is a fairly general phenomenon and that both de- 

 structive and regenerative processes may be modified. This is apparent 

 particularly when protective effects can be quantitated in terms of radiation 

 dose-biological response parameters. Although the desirability of such 

 evaluation is perhaps obvious, it is worthy of emphasis in view of inferences 

 that are sometimes drawn from single dose determinations or semi-quanti- 

 tative measurements. Under appropriate experimental conditions, cysteine 

 and other sulphydryl substances have been shown to diminish many of the 

 effects of gamma and X-irradiation, e.g. lethality of bacteria, isolated cells 

 and animals, chromosome breakage in plant cells, mitotic block in corneal 

 epithelium, decreased nucleic acid turnover, enzymic changes in spleen and 

 thymus, lenticular opacities, epilation, splenic atrophy, leucopenia and 

 anaemia^' ^^. Cysteine affords a rather uniform protective action against 

 lethality, splenic involution, lymphopenia and granulocytopenia in the 

 intact animaP and the killing of thymocytes and ascites tumour cells in 

 vitro^^. 



It is worth noting that d and 1 cysteine are equally effective in mice but 

 that all sulphydryl substances are not protective to animals, perhaps because 

 of differences in their biological fate. The latter is a complicating factor, 

 not infrequently overlooked, which must enter into interpretation of in vivo 

 findings. The action of cysteine and p-mercaptoethylamine in mice appears 

 to be similar^-. The latter is more efficient but is also more toxic than the 

 former. It is of interest that maximally tolerated doses of each give equiva- 

 lent protection against acute radiation lethality ; suboptimal amounts 

 seem to be completely additive. Further indication of their similarity of 

 action is apparent also from enzyme protection studies. As shown by 

 Petersen and DuBois^^ prior administration of cysteine or [i-mercapto- 

 ethylamine in roughly equimolar amounts has a comparable effect on the 

 radiation-induced increase in adenosine triphosphatase and 5-nucleotidase 

 activities of spleen and thymus. 



The degree of protection is a function of cysteine dose and is independent 

 of radiation dose, at least within certain limits. The effect is manifest, 

 therefore, by a change in slope of the radiation dose-response curve. 

 Results obtained in mice with a split-exposure procedure, in which a standard 

 dosage of cysteine was given between two radiation fractions or a propor- 

 tional amount preceded each fraction, suggest that (7) irradiation just prior 

 to cysteine administration does not influence the protection against subse- 

 quent exposure ; (2) the lethal potential of small dosages of radiation cannot 

 be reversed by cysteine ; and (5) the protective action of two suitably 

 spaced cysteine injections is additive^. Essentially similar relationships 

 have been found for the oxygen effect in plants i*. Unlike the picture with 

 animals, there is a definite, although lesser, protective effect when cysteine 



106 



