124 MICROSOMAL PARTICLES 



Hutchinson, Morowitz, and Kempner [2]. If sources of radiation are available, 

 the method is, relatively speaking, technically easy, and therefore attractive. It 

 is necessary, however, to be aware of the uncertainties of interpretation, to be 

 sure that misleading deductions have not been made. The use of ionizing 

 radiation to study cellular processes has been under intensive study in this 

 laboratory for several years [2, 3, 4, 5, 6], and therefore a summary of the find- 

 ings seems worth while, so that the validity of the conclusions can be estimated. 



The two major classes of biological macromolecules, proteins and nucleic 

 acids, appear to be very sensitive to ionizing radiation. An enzyme molecule 

 loses its activity if a cluster of ions forms anywhere inside the molecule; an 

 antigenic protein loses its ability to combine with antibody if such a cluster 

 forms in a volume somewhat smaller than that of the protein. DNA, as trans- 

 forming principle, loses its function if such a cluster forms within a unit of 

 about 300,000 molecular weight. If irradiations are carried out in solution, re- 

 action products can move around, and they may have marked inactivating 

 power. Studies by Hutchinson [7] on yeast cells in various conditions of mois- 

 ture indicate that in the cell such reaction products carry their effectiveness 

 over a distance of only 30 A. All these effects can be modified by factors of 

 about 2 by several environmental conditions, notably oxygen tension and degree 

 of aggregation between protein molecules. Thus, until the final sorting out of 

 cause and effect is accomplished, the statistical interpretation of radiation effects 

 must be considered to be approximate only. Even so, it is valuable as an aid 

 in studying an important, inaccessible process. To give some idea of the va- 

 lidity of the conclusions drawn we reproduce here a diagram, prepared by 

 W. R. Guild, showing the relation between the "target molecular weight" de- 

 rived from the statistical radiation analysis of radiation inactivation and the 

 accepted molecular weights. Since the diagram is a log-log plot, it should not 

 be viewed over-optimistically, but the reason can be seen for the claim that a 

 factor of 2 is normally all that is involved as error. 



In order to gain the maximum information from irradiation studies, at least 

 three, and preferably more, types of irradiation should be carried out: (1) Irra- 

 diation by radiation sources very rich in fast electrons, as, for example, electrons 

 themselves, of energy 0.5 Mev or more, or y-ray sources of energy in excess of 1 

 Mev, where the secondary electrons due to Compton recoil and photoelectric ab- 

 sorption have energies, in the main, in excess of 0.5 Mev. (2) Irradiation by 

 heavy particles of variable rates of energy loss. Such particles have dense ioniza- 

 tion, largely confined to tracks, and they give a different distribution of local en- 

 ergy releases from fast electrons. Heavy particles of at least two energies should 

 be used, to give a range of separation of energy releases. In our experiments we 

 have employed cobalt 60 y radiation, deuterons of varied energies, and a par- 

 ticles as bombarding agents. The results show that the uptake of methionine 

 into the protein fraction (fraction insoluble in cold trichloroacetic acid) is re- 

 tained unless very heavy irradiations are employed, and the sensitive region fits 

 very well with a sphere of radius 130 A. For the uptake of proline into the 



