K.\i)io-PRorKc:ri\K AcrnoN of 5-HV^RC)x^ i K^•l'^AMI\K 



the rndio-jiiotectivc cflrct of hislaniiiic in rats, it has no significant cfTcct on 

 5-OHl' protection. C^onversely n-OH T antinietahohtes did not significantly 

 reduce the rather weak protective action of histamine in rats. 



CH3 

 CH==C-CH2-CH2-NH2 HC CH2-N-(CH3)2 



Histamine Promezathine 



Conclusions 

 In summarizing the resuks of experiments presented here, it appears that 

 radio-protection by 5-OHT and histamine is intimately related to specific 

 receptor-metabolite reactions in competent cells. 



If the amine acted as a competitive free radical, one would suspect that 

 (?) a sterically similar antimetabolite such as BAS, with similar physico- 

 chemical properties and chemical activity, should result in radio-protection 

 in vivo and in vitro; (ii) the free presence in the cell, of an antimetabolite, should 

 neither decrease the radio-protective effect of the respective metabolite nor 

 an unrelated metabolite. 



It is difficult to reconcile the findings presented, with this hypothesis of 

 radio-protective mechanisms. Also it seems from our studies in animals 

 depleted of histamine, 5-OHT and catechol amines, that the 'bound' endo- 

 genous entity in cells does not confer cellular radio-resistance. Its change to 

 a 'free' form in vivo, is necessary, although decrease in sensitivity of specific 

 vasoconstrictor receptors, allows for substantial protection to persist. How- 

 ever, apart from the latter finding, most of the results obtained are largely 

 consistent with the theory, that radio-protection in vivo is due to anoxia of 

 tissues — possibly secondary to bronchoconstriction and vasoconstriction, but 

 more likely the result of a histotoxic anoxia. This decision will rest on the 

 results in vitro with simpler systems, and other experiments to be detailed later. 



It would seem that certain experiments are indicated. Particularly, the 

 effect of metabolites, respective afid unrelated antimetabolites, singly and in 

 combination, should be examined for protective action in vitro using polymer 

 solutions, for comparison \vith the results in the intact animal. 



/ am indebted to Miss M. Haas, for experimental results shown in Figure 2. Gifts 

 of 5-hydroxytryptamine, LSD and BOL were kindly supplied by Sandoz Ltd., Marsilid 

 {iproniazid phosphate) by Roche Products Pty. Ltd., and l-benzyl-2,5-dimethyl 

 serotonin (BAS) by Merck & Co. Ltd., New York. My colleague, Mrs. K. Elliott, 

 assisted in the experimental procedures, and her invaluable help is gratefully acknowledged. 



REFERENCES 



^Alexander, P., Bacq, Z. M., Cousens, S. F., Fox, M., Herve, A. and Lazar, J. 



Radiation Res. 2 (1955) 392 

 -Bacq, Z. M. and Ai.kxander, P. Fundamentals of Radinf)inlngy : Butterworths. 

 London, 1955 



176 



