186 ASPECTS OF BIOCHEMICAL EFFECTS 



of H2O2 is the mechanism of biochemical effects, lest progress made in 

 other directions be obscured or even entirely lost. There is no doubt 

 that H2O2 in certain cases can account for some of the effects (17), and 

 there the action of H2O2 is a factor which tends to complicate the un- 

 raveling of the mechanisms. There are, however, sufficient examples of 

 substances not sensitive to H2O2 which show marked radiosensitivity, 

 and again examples where it can be shown that H2O2 formed by the dose 

 applied can only to a minor part account for the end effect. Moreover, 

 catalase, one of the most powerful enzymes ubiquitously present in tissue, 

 should take care of H2O2 formed unless the H2O2 reacts before it can be 

 destroyed, or else the catalase would be destroyed by radiation in prefer- 

 ence to H2O2. If one wishes to consider further examples of possible 

 "poisons" formed by radiation, one could think of ammonia, which can 

 be formed with a high ionic yield from proteins and amino acids, or the 

 formation of H2S from cysteine and glutathione, recently discovered by 

 us (19), which could have toxic effects on biological components. One has, 

 of course, to be careful not to regard any new single reaction as of over- 

 riding importance; rather the contrary is probably nearer the truth, that 

 is that the sum total of the derangement of the balance and interplay 

 of cellular processes is what matters. On the other hand, the possibility 

 that one "poison" or another may play a vital part is supported by the 

 more recent discovery of mitotic and radiomimetic substances. But 

 these can be introduced into the cell interior only with difficulty and 

 in a limited way, whereas radiation knows of no permeability barrier 

 and can perform with ease chemical reactions within the cell. 



I think what I have said has shown that the solution of the problem 

 of the biochemical effects of ionizing radiations is still in its initial stage. 

 Are we justified in looking for a few key reactions, or are the effects 

 rather the sum of a multitude of processes? Only more intensive work 

 can decide this question. A review by Monne of the progress made in 

 the elucidation of the structure of protoplasm pictures a highly organized 

 system of fibrils consisting of minute granules, chromedia, which alter- 

 nate with interchromedia, the whole sustained in a dynamic equilibrium. 

 These chromedia consist partly of enzymes and can be separated, ac- 

 cording to Monne (18), from minced cells and analyzed by exact chemi- 

 cal methods. There would thus be a chance of testing radiation effects 

 by isolating the chromedia before and after irradiation. We may hope 

 that the cooperation of cytologists and cytochemists will help to put 

 some of our speculative conclusions on a firm basis. 



