CYSTEAMINE 



DISCUSSION ON PAPERS BY PATT, VERLY AND 



HOLLAENDER 



Z. M. Bacq : I fully agree with Hollaender that the metabolic actions of cysteamine 

 and cystamine are very important. The differences between cysteamine and 

 cysteine on which we have often insisted are the following : 



Cysteamine, just like all amines, cannot be directly incorporated in proteins or 

 in coenzyme A. Cysteamine depletes the liver of its glycogen ^ and the suprarenals 

 of their ascorbic acid^ ; it liberates in the blood several reducing substances of which 

 only ascorbic acid has been identified^. Cysteine has none of those actions. 



I am not surprised that, as Hollaender showed, any change in the structure of 

 cysteamine decreases its protective power. We have established both in mice* 

 and in a synthetic polymer in vitro^ that the structure which favours chelation also 

 favours protection against ionizing radiation. If one substitutes anything to one or 

 several hydrogens in cysteamine, one decreases the chelating power of the molecule. 

 We have observed that S-methyl, S- or N-mono or diacetyl cysteamine are inactive 

 or less active^ ; the acetyl derivatives are still active because they are hydrolized m 



30 min. 



I I I I I I I I I I I I I I I I I I I I I I 

 8 10 12 U 76 18 20 22 21 26 28 



Jours apres irradiation 

 Figure 1 



the body and liberate cysteamine. Even the physiological N-pantothenyl cysteamine 

 (= pantetheine, a growth factor for micro-organisms and a fragment of CoA) is 



inactive^' ®. 



We think * that the general mechanism of action of the radioprotection in aqueous 

 systems is that of a competition for free radicals rather than an energy transfer, but 

 this is a theoretical discussion. We do agree with Patt, that the protection occurs 

 at a very early stage, and is quantitatively the same. The observed differences 

 can be accounted by the fact that cysteamine when injected to mammals does not 

 distribute itself equally in all tissues. The spleen, the bone marrow concentrate it 

 (Eldjarn*) ; the liver destroys it actively (Verly), the testes on the contrary are at 

 a much lower level than the blood (Eldjarn). We also believe that anoxia is not a 

 possible component of the protection by cysteamine, because cysteamine protects 

 dog's reticulocytes in vitro\ i.e. cells containing haemoglobin saturated with Og, and 



* L. Eldjarn presented a paper the details of which will be published elsewhere : 



(1) Eldjarn, L. and Nygaard, O. ' Cysteamine-cystamine : Intestinal absorption, distri- 

 budon among various organs and excretion.' Arch, inteniat. de Physiol., in press. 



(2) Nygaard, O. and Eldjarn, L. ' Cysteamine-cystamine : Effect on uptake and turn- 

 over of radioactive iodine by the thyroid gland in rat.' (To be published.) 



(3) Shapiro, B. and Eldjarn, L. ' The effects of ionizing radiation on aqueous solutions 

 of cysteamine and cystamine.' (To be published.) 



(4) Shapiro, B. and Eldjarn, L. ' The possible mechanism for the decomposition of 

 cysteamine and cystamine by ionizing radiation.' (To be published.) 



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