THE NATURE OF THE PEROXIDE-LIKE SUBSTANCES FORMED IN MICE BY X-RAYS 

 Table I. — Extent of reaction of various peroxides, etc. with cadmium reduced brilliant cresyl blue 



Pure Substances 



Butyric Aldehyde 



Benzaldehyde 



Ethyl Hydroperoxide . . 



tert. Butyl Hydroperoxide 



Tetralin Hydroperoxide 



Cyclohexyl-l-Hydroxyl-1 -Hydroperoxide 



Benzoyl Peroxide 



Hydrogen Peroxide 



Diethyl Peroxide 



Percentage Theoretical 



R.T. 





 



111 

 108 



43 

 110 

 108 



67 

 



100° 





 



111 



108 



43 



110 



108 



67 



54 



Impure Substances 

 {Autoxidized) 



Ethyl Oleate 



Isoprene 



Diacetyl 



Indophenol 



R.T. 



100 

 25 

 25 



100° 



(100)* 

 (100)* 

 (100)* 



Brilliant cresyl blue 



R.T. 



95 

 2-1 



24 



100° 



95 

 9-3 



100 



* Arbitrary standard. 



hydroperoxide group and one cyclic peroxide group are introduced per 

 molecule. This would be approximately consistent with our findings in 

 mouse extract if the surprising assumption were made that practically the 

 whole of the X-ray induced autoxidation in the mouse involves squalene or 

 similar substances (1,5 dienes) rather than oleic or linoleic acids (monoenes 

 or 1,4 dienes). Squalene has been known for some time to occur in sebum 

 and to be mainly responsible for skin peroxides, and although only traces 

 have been found inside the mammalian body Langdon and Bloch* have 

 proved that it is an intermediate in the synthesis of cholesterol from acetyl 

 groups through co-enzyme A, with the rapid turnover time of about 30 

 minutes. This suggests that radiation may act through chain autoxidation 

 of squalene and its near neighbours in the metabolic pathway, leading 

 perhaps to the formation of abnormal sterols or to blocking of the formation 

 of normal sterols, or to interference with some function of squalene itself, 

 e.g. in cell membranes, or to direct toxicity of squalene peroxide. In any 

 case, if the primary hypothesis is true, it might be expected that temporary 

 blocking of squalene synthesis via acetyl CoA might diminish radiosensitivity 

 by temporarily diminishing the steady-state concentration of squalene and 

 its neighbours. Bacq has pointed out that cysteamine, probably the best 

 known antiradiation drug, is a component of co-enzyme A, and seemed at 

 one time to imply that it might act by helping to restore damaged co- 

 enzyme A. The new squalene hypothesis suggests that cysteamine and 

 other — SH compounds and amines may act in the opposite direction, 

 e.g. by preventing the oxidation of lipoic acid to the disulphide form needed 

 for transferring acetyl groups to co-enzyme A {cf. Gunsalus^). A good 



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