A Physical Mechanism for the Inactivation of Proteins by Ionizing Radiation 263 



this great sensitivity with a disruption of complex organization, but it is not 

 known which of the two varieties is so highly susceptible. Indeed, both are 

 likely ultimately to be involved. 



In the case of the functional organization, many proposals have been made 

 concerning the initial point of attack. Thus, the destruction or transformation 

 of sulfur-containing groups, of critical enzymes, and of various other essential 

 constituents present in small or in trace amounts, or the production of powerful 

 poisons, have been implicated. The answer is unlikely to be unique, and from 

 its pursuit, which must involve biological questions of the highest complexity, 

 most of the contributions of radiobiology to the science of biology probably will 

 devolve. 



The degradation of crucial macromolecules by ionizing radiation is, on 

 the other hand, amenable to in vitro experimentation and to purely physico- 

 chemical theoretical analysis. It is the purpose of this paper to examine the 

 possible explanations for such disruption from a simple physical point of view, 

 and to present and investigate one mechanism which is based realistically upon 

 physical and chemical principles and is in full accord, at least qualitatively, 

 with the results of experiment. 



A paramount experimental fact is the exceedingly great sensitivity of these 

 macromolecules to ionizing radiation compared to their sensitivity to ultraviolet 

 light. This fact is without parallel in the radiation chemistry of simple organic 

 or inorganic systems, and no clue is provided by the conventional theory of 

 the interaction of swiftly moving charged atomic particles with simple molecules. 

 It is therefore imperative to reanalyze this interaction, with specific regard to 

 the character of the absorbing medium. 



The primary processes through which the radiation affects the medium cannot 

 differ qualitatively from those in a simple molecular system. In the case of 

 proteins, for example, the very weak bonds which bind the polypeptides together, 

 and even the peptide bonds, must be essentially without influence on the optical 

 dispersive properties of the medium,* and hence the varieties of energy transfer 

 from charged particles, their statistical distribution, and even their spatial dis- 

 tribution will differ only slightly from the corresponding quantities for a simple 

 mixture of amino acids having the same over-all composition. (This statement 

 is not correct with respect to the energy dissipated by moderation of the subex- 

 citation electrons, but that portion of the energy transfer cannot alone be 

 responsible for the great sensitivity.) 



Many of the events immediately subsequent to primary absorption of the 

 incident radiation, on the other hand, must differ strikingly from those in a 

 simple system. The reason (5) is that the course of such events is determined 

 by the dielectric properties of the medium, and these, in contrast to the behavior 

 at high (optical) frequencies, are profoundly different for a condensed system 

 composed of highly polar molecules. Ionization in nonpolar substances is 

 usually followed more or less quickly by recombination, so that the chemical 

 consequences of absorption of ionizing radiation are very similar to chemical 

 changes induced by ultraviolet light of appropriate frequency. In a system 



* This is even approximately true for the near-ultraviolet absorption spectrum, which is 

 more sensitive to such bonds than the excitations of greater energy that dominate the phenomena 

 of energy transfer from ionizing radiations. 



