REMARKS CONCERNING SULPHYDRYL 



PROTECTION AGAINST MAMMALIAN 



RADIATION INJURY 



Harvey M. Patt 



Division of Biological and Medical Research, Argonne National Laboratory, Lemont, 



Illinois 



The modification of radiation effects by chemical agents has been and 

 continues to be an important focus in radiobiological investigation. We 

 have learned that a number of substances have the capacity for modifying 

 a variety of responses to ionizing radiations. Viewed in an historical 

 perspective, a number of landmarks appear along the way, but it is perhaps 

 sufficient for our purpose simply to recall the early interest and accomplish- 

 ment in this area. Armed with some understanding of the radiolysis of 

 water and cognisant of its potential contribution to the development of 

 radiation injury in plants and animals, present investigators have greatly 

 extended the possibilities for modification of radiation effects. The list of 

 chemicals that protect against one or another radiation effect ranges from 

 sugar to alcohol, from the familiar epinephrine to the esoteric para-amino- 

 propiophenone. It includes sodium nitrite, cyanide, and pitressin as well 

 as cysteine, glutathione, cysteinamine and other amines. These substances 

 are by no means equally effective and, no doubt, differ somewhat in their 

 mode of action. The more recent developments have been reviewed else- 

 where^. We may note in passing, however, the first definitive experiments 

 on the oxygen effect by Thoday and Read^-^ and the chemical protective 

 effects in animals described by our own group^- ^ and by Chapman^- ' 

 BAcq^' ^ and their collaborators. 



While certain of the facts of chemical modification are reasonably well 

 established, the mechanisms underlying the facts are frequently obscure or 

 at best only circumstantial. We may define chemical protection for our 

 purpose as the reduction of a given response by administration of a suitable 

 agent prior to irradiation. One is inclined generally to interpret protective 

 phenomena of this sort in radiochemical rather than in biological terms. 

 This implies, as in the case of anoxia, that the protection is due, for the most 

 part, to a decrease in the biological effectiveness of the radiation rather than 

 to a basic change in the sensitivity of the responding system. We will be 

 concerned here mainly with the effects of cysteine which, in certain respects 

 at least, may be thought of as a characteristic example of this type of pro- 

 tection. Other pharmacological agents that are related to oxygen avail- 

 ability in one form or another probably also fall into this classification. 

 This may obtain even for the paradoxical cyanide, which protects some 

 species but not others, potentiates effects on isolated tissues and is evidently 

 neutral to suspensions of isolated cells^. 



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