MANNER OF PRODUCTION OF MUTATIONS 599 



the one hand, and of Thoday and Read and those following them, on the 

 other hand, have shown clearly that the activated products of the irradia- 

 tion of water which contains dissolved oxygen, and even of water without 

 oxygen when the activations are crowded enough, are capable of causing 

 both point mutations and chromosome breaks. In fact, the evidence 

 shows that under ordinary circumstances a considerable majority of the 

 mutations and breaks produced by ionizing radiation are brought about 

 in this way rather than via a direct hit on the genetic material. Results 

 of chemical studies such as those made by Fricke, by Barron and by 

 Dale have made this finding more understandable. It is true that, with 

 ultraviolet of wave lengths too long to dissociate water directly, the 

 initiating activation may usually be on the nucleic acid or in some cases 

 on the protein of the chromosomes themselves, but even in this case it is 

 conceivable that the activation may sometimes be transferred to another 

 constituent, which then in its turn reacts back upon the genetic material. 



The dissociation of water is only the first step in the major pathway 

 leading to mutagenesis by radiation. The studies on irradiated medium, 

 on mutagenesis by substances having readily activable oxygen, and on 

 the promotion or interference with mutagenesis by other influences, 

 especially by those applied after irradiation, have shown that following 

 this dissociation there may be additional steps intervening before the 

 completed point mutation or break and that substances of varied types 

 may alternatively serve as intermediaries here. Undoubtedly, in some 

 cases, hydrogen peroxide is an important substance in this class. 



The existence of these intermediate steps provides means by which the 

 occurrence of mutagenesis as a consequence of irradiation may be to some 

 extent controlled and whereby it has also been opened to further analysis. 

 In some directions this field of investigation ramifies so as to join with 

 the whole intricate subject of oxidative and antioxidative enzymes and 

 metabolism, inasmuch as the processes therein involved affect the dis- 

 tribution and fate of the primary products of irradiation, and of the 

 secondary, tertiary, etc., products. Thus, although certain general 

 principles are already emerging with regard to the effects of accessory 

 physical and chemical treatments (such as the protective action of some 

 sulfhydryl-containing substances), many special situations also intervene, 

 varying from one type of organism to another and from one type of tissue 

 or cell stage to another according to the pecuHarities of their structure 

 and reactions in destroying or producing or affecting the passage of differ- 

 ent substances or in responding to given physical influences such as 

 temperature, pressure, or visible light. For this reason the study must 

 be carried out on varied biological material. 



It is an expression of this situation that in certain bacteria the pathway 

 from primary activation to mutation may be long spatially, whereas in a 

 number of higher organisms there is evidence that (with ionizing radiation 



