272 Robert Platzman and James Franck 



interpreted as stemming from the portion of the spectrum that is subcritical. 

 (Butler has shown (3, 16) that DNA is also more sensitive to thermal destruc- 

 tion after irradiation.) Fricke has even specifically resolved the thermally 

 labile component into a number of fractions with differing thennal response (23). 

 In the case of ovalbumin irradiated with gamma-rays he found the denatured 

 product to be less degraded than the thermally denatured product; this is as 

 expected, since large-scale unfolding can only occur thermally. Another mani- 

 festation of the spectrum of radiation injury is the differing reaction to post- 

 irradiative environment that is occasionally observed. This phenomenon, of 

 which the after-effect is a special case, is related to the effect of radiative environ- 

 ment, discussed above, but it clearly involves a later phase of the injury — in 

 particular, partial damage will have been stabiUzed by closure of many hydrogen 

 bonds, although often in an incorrect way. (This can be inferred from the very 

 low values of lieats of denaturation, which show that in thermal denaturation 

 most of the bonds do fonn again after unfolding.) Such disordered molecules 

 may be further altered by certain external influences and may be restored, at 

 least in part, by others. It has been remarked (15) that a dependence of the 

 inactivation of irradiated hemoglobin (and other proteins) on the pH of the 

 solvent in which they are dissolved after irradiation is anomalous, but according 

 to the views set forth here such a dependence is not unexpected. 



In the above discussion the term 'localized electric charge' was used in place 

 of 'ionization act' to denote the center of the polarization wave. The motion 

 of an electron vacancy produced by ionization in a protein has been the subject 

 of much conjecture, but a cogent analysis has yet to be made. Although it is 

 certainly true that in (for example) a simple, isolated organic molecule, the 

 precise designation of an original site of ejection of a valence electron has little 

 meaning, this cannot be taken as proof that an electron vacancy has unlimited 

 ability to migrate along the skeleton of a protein or similar macromolecule. 

 One reason is the low degree of symmetry of the molecule, and its greatly 

 differing regions of potential. Another, which often is overlooked, is the 

 influence of the external polarization on this migration. The electronic part of 

 the polarization sets in almost immediately at ionization, and the various low- 

 frequency varieties follow as discussed above. All of them severely limit the 

 mobility of both positive and negative charges. It therefore appears unlikely 

 that an electron vacancy can cross a secondary linkage, or possibly, indeed, 

 even a peptide bond. In the case that several electron vacancies are produced 

 within the same molecule, whatever motion may be possible must enhance the 

 potency of the effect for disordering, for the coulomb repulsion will tend to 

 separate the final sites of localization, thus preventing diminution in effectiveness 

 by too great confinement. 



It should be emphasized that the mechanism developed in this paper applies 

 strictly only to the effect of radiation on an isolated macromolecule, a somewhat 

 hypothetical situation approximated in experimental work on 'dry' proteins 

 (1, 4). Immediate effects of the environment have also been touched upon. 

 For proteins in solution, or in living cells, indirect effects, of a simple or complex 

 chemical nature, must also contribute to the observed behavior, and no general- 

 izations regarding the relative potency of the two, except that neither is likely to 

 be negligible, seem warranted. 



