MUTAGENESIS 125 



examined 300 Caucasians from New York City without finding any 

 cases. We have also examined hemolysates from 63 Japanese in Seattle 

 without luck. 



Glass: Will these familial enzymes act on organic varieties of 

 peroxide, do you know? 



Auerbach: If it is true that formaldehyde when used in solution 

 acts by forming the addition compound with hydrogen peroxide, and 

 that this addition compound is the actual mutagen, then the enzymatic 

 constitution of the organism becomes important. On the theory that 

 catalase poisoning would enhance the mutagenic effect of injected 

 formaldehyde in Drosophila, Sobels (66) pretreated flies with potas- 

 sium cyanide. He did increase mutation frequency, and even obtained 

 some mutations in females, which ordinarily are quite refractory to 

 the treatment with formaldehyde. 



Freese: I would like to pose a problem here. Peroxides may act either 

 as such or as radicals which are derived from the peroxide. Since 

 organic peroxides are active mutagens, while hydrogen peroxide itself 

 does not seem to be effective, the possibility of radical action seems 

 more likely. 



Lederberg: I certainly agree with Freese on that point, but we did 

 find that peroxide was quite effective in inducing the segregation of 

 diploid heterozygous bacteria, which would indicate that it is at least 

 inducing lethal lesions (44). We haven't ourselves studied it for its 

 mutagenic effect, but it may cause widespread damage. 



Auerbach: Hydrogen peroxide? 



Lederberg: Yes. Whether it is hydrogen peroxide by the time it 

 reaches the DNA is an entirely different question. It may be entirely a 

 matter of dose and concentration and what it can react with as a 

 carrier on the way in. Most of the bacteria that have been used in 

 genetic research do have catalase, and I think this is something of a 

 problem. 



In following up what Dr. Glass had to say, I think it should be 

 remembered that quite a number of compounds do have catalase 

 activity to varying degrees. Even inorganic iron does, to a very sub- 

 stantial extent, and heme and hemoglobin do have a measurable 

 catalase activity. It may run throughout difficult quantitative ques- 

 tions in trying to decide what the role of catalase is in protecting 

 mutagenic material. 



Auerbach: In the Texas experiments by Stone, Wyss, and Haas (69), 

 it was not hydrogen peroxide which was effective, but organic peroxides. 



I come now to another subject altogether. This is one which I have 



