INTERMEDIATE STEPS OF MUTAGENESIS 317 



in the mutagenic action of radiation may be said to have started in 

 earnest only three years ago, when Stone and his coworkers, Wyss, 

 Clark, Haas, Wagner, Haddox, and Fiierst, succeeded in inducing bac- 

 terial mutations by irradiating the medium with ultraviolet, and shortly 

 afterwards adduced evidence that the effect was to be attributed to 

 peroxides, including organic peroxides, formed under the influence of the 

 radiation. This momentous discovery has since been extended to Neuro- 

 spora, both by Dickey, Cleland, and Lotz (13), and by Wagner and 

 others working with Stone (76), and the evidence has made it probable 

 that many peroxides, or perhaps organic peroxides in general, are mu- 

 tagenic. Moreover, influences which would favor the formation of per- 

 oxides by radiation, such as supplying additional oxygen, or blocking 

 the utilization of oxygen in the ordinary metabolic routes, have been 

 found to increase the rate of production of mutations by radiation, 

 whereas, conversely, the opposite conditions depress the process. 



The independent discovery by Thoday and Read (69) that the pro- 

 duction of chromosome aberrations by radiation is positively corre- 

 lated with the amount of oxygen present is in striking agreement with 

 the above results. The further finding by Thoday et al. (70) that the 

 oxygen has less influence on such changes when radiation is used which 

 gives tracks more densely crowded with ions has been thought to mean 

 that the active radicals were in this case more c^uickly neutralized by 

 by their complements derived from other ionizations. An alternative or 

 additional reason would seem to be that the denser tracks have concen- 

 trations of ions further beyond the optimal concentration for ratio of 

 breakage effects to ionizations: that is, many of the ions in the denser 

 tracks are supernumerary in that they are unable to produce recordable 

 breaks in the given chromosome region because the effectiveness of other 

 ions near-by has pre-empted their field. Thus a reduction in the con- 

 centration of active radicals in the latter case (caused by less O2) has 

 less effect than when the ionizations are more scattered. It will be seen 

 that, in this interpretation, it is taken for granted that there is a certain 

 degree of localization of much of the mutagenic effect, despite the fact 

 that, in Stone's work at least, some part of the effect must have a long 

 range of diffusion. Reasons for inferring this localization were given on 

 p. 313. It is fortunate, however, for purposes of analysis, that not all 

 the effect is so localized, in all material. 



The studies of Barron (5, 6) on biochemical and cytoplasmic effects 

 of radiation, and more particularly his discovery of the high radiosensi- 

 tivity of sulfhydryl groups and of enzymes containing them, appear, both 

 in their essential features and in various details, to fit very well into the 

 same general scheme, for the change induced in the sulfhydryl groups is 



