MANNER OF PRODUCTION OF MUTATIONS 551 



of the action of such enzymes would tend to lower the ultraviolet- 

 induced-mutation rate, whereas the inactivation of these enzymes would 

 increase the rate. This is one possible basis for the enhancing and 

 reparative effects noted in the work on the influence of posttreatments of 

 light, dinitrophenol, anoxia, and temperature on the ultraviolet-induced- 

 mutation rates. In this connection it may be recalled that light applied 

 to the bacteria was found to prevent to some extent the mutagenic effect 

 of irradiated and of hydrogen peroxide treated media upon them. 



Since some transitory peroxides and active radicals such as OH are 

 produced even in normal intracellular metabolism, especially in hydrogen 

 peroxide-producing oxidations carried on by flavoproteins, a part of the 

 spontaneous-mutation frequency also may well be of this origin, as Wyss 

 and Stone and their co-workers have pointed out. In that case not only 

 peroxides but also agents which foster the production or the persistence 

 of peroxides in the cell, as for instance by shunting more of the oxidations 

 into the control of the flavoproteins, might have a perceptible effect in 

 increasing the frequency of mutations arising in the absence of radiation 

 or of artificially applied peroxides. Evidence of this was obtained in the 

 finding of Wyss et al. (1948) that azide, which inhibits catalase, cyto- 

 chrome oxidase, and some other enzymes, markedly increased the spon- 

 taneous-mutation frequency in Staphylococcus. Similarly, in Neurospora, 

 Wagner et al. (1950) found that cyanide, which likewise is an inhibitor of 

 catalase and related enzymes, caused a marked increase in mutation fre- 

 quency in the absence of ultraviolet treatment, although, strangely, this 

 substance did not appear to act synergistically with ultraviolet. 



In further work on Staphylococcus, Clark, Wyss, and Stone (1950) 

 found that menadione, a vitamin K analogue which blocks sulfhydryl 

 groups on enzymes and thus inactivates the enzymes containing them, 

 markedly increases the mutation frequency occurring in the absence of 

 irradiation. It was found possible to block the effect of the menadione in 

 turn by the protective action of cysteine and other compounds which 

 supply sulfhydryl groups. It would be of interest to know whether this 

 mutagen, like mustard, works synergistically with ultraviolet. As 

 Barron and co-workers (Barron, Dickman, and Singer, 1947; Barron and 

 Dickman, 1949; Barron et al., 1949; Barron and Flood, 1950) have shown, 

 enzymes and other proteins containing sulfhydryl are inordinately sensi- 

 tive to radiation. It has therefore been suggested that they may con- 

 stitute the main point of attack of radiation on the cellular metabolic 

 system and perhaps even, directly or indirectly, on the genes. Seem- 

 ingly opposed to this, however, are the findings of Auerbach and Robson 

 (1947) and of Auerbach (1950b) that neither lewisite nor chloropicrin, 

 which are very potent in attacking SH groups, are mutagenic in 

 Drosophila. 



The work cited in the preceding paragraphs shows that studies of 



