LOCALIZATION OF RADIATION EFFECTS 263 



specific atom groupings, such as phosphate in nucleoprotein, vary con- 

 siderably in response to radiation. Thus, data on inactivation of phage — 

 whether derived from x-ray experiments or from experiments in which 

 P^^ is incorporated into phage — indicate that, although one "hit" or 

 event may be sufficient to inactivate a whole phage molecule, numerous 

 such events occur before inactivation takes place. In x-ray inactiva- 

 tion, for instance, the survival curve shows the "one-hit" type of process, 

 while dosage measurements indicate approximately 75-100 ionizations 

 occurring inside each phage. Experiments employing incorporation of 

 P^^ directly into the phosphate of phage yield data of a similar nature, 

 but they reveal besides that a few specific bond sites, that is, phosphate 

 groups, cannot be disturbed without inactivation of the molecule as a 

 whole. Only when the structure of nucleoprotein and the disposition 

 of phosphate within the viable molecule are understood will it be pos- 

 sible to propose definite mechanisms for inactivation by radiation inter- 

 action with the P atoms of the nucleoprotein. 



Some extensions of these procedures to other enzymes and systems 

 come to mind. A few systems which might be examined by these 

 methods include: 



1. Inactivation of enzymes containing more or less firmly bound co- 

 factors, that is, triosephosphate oxidase of rabbit muscle with its one 

 molecule of diphosphopyridine nucleotide (1). 



2. Changes in physicochemical properties of proteins into which large 

 amounts of phosphate can be incorporated, as in so-called phosphopro- 

 teins of yeast. 



3. Use of S^^ in studying radiosensitivity of H — S and S — S bonds in 

 proteins, such as insulin. 



4. Possible localization of short-lived C^^ in carboxy-peptide bonds 

 by biosynthesis of protein from labeled CO2 or carboxyl-labeled amino 

 acids. 



5. Comparison of products obtained by x-ray bombardment of and 

 by P^^ incorporation into simple molecules like glucose-1-phosphate and 

 adenosinetriphosphate. 



Ramifications of considerable potential importance may also be ex- 

 pected from exploitation of the suggestion by Hershey that the relation 

 between survival time and P^^ content of phage be utilized for distin- 

 guishing distributions of P^^ in heterogeneous phage populations, and 

 in particular for distinguishing parent from progeny phage in experi- 

 ments designed to establish mechanisms of phage reproduction. 



The future exploitation of these methods depends primarily on the 

 availability of radioactive elements with high specific activity. In ex- 

 tending researches of the type described, P^^ samples with specific 



