IONIZING RADIATIONS AND THIOL GROUPS 217 



Ionizing Radiations and the Thiol Groups of Cells 



When in 1943 I was asked to study the mechanism of action of 

 ionizing radiations, I was struck by the similarity of response produced 

 by such seemingly different agents as mustard gas, nitrogen mustard, 

 and x-rays. All three agents produced leukopenia, hemorrhagic mani- 

 festations, mutations, and inhibition of mitosis and of cell division. 

 Since the first two have one common chemical property, that of reacting 

 easily with thiol groups to form alkylated compounds, and in 1930 

 Rapkine (1) had demonstrated that — SH groups are necessary for 

 mitosis and cell division, it was reasonable to postulate that one of 

 the effects of ionizing radiations was the destruction of the thiol groups. 

 Such destruction would be caused by the oxidation of — SH groups to 

 the — S — S bond, a process brought about by the products of irradiation 

 of water: the radical OH, a product of the primary ionization reaction; 

 the radical O2H; and H2O2 formed in the presence of oxygen. Thus, 

 four — SH equivalents would be oxidized per ion pair: 



2— SH + 20H = — S— S— + 2H2O 



2— SH + 2O2H = — S— S— + 2H2O2 



2— SH + H2O2 = — S— S h 2H2O 



The first experiments to test the plausibility of the hypothesis were 

 performed on thiol enzymes, that is, those enzymes that require the 

 presence of — SH groups for activity. Thiol enzymes, such as phospho- 



TABLE 1 



Effect of X-Rays on the Activity of — SH Enzymes 



(From Barron et ah, J. Gen. Physiol, 32: 537, 1949) 



X-Ray Inhibi- Reactiva- 

 Dose, tion, tion, 



Enzyme r % % 



