MUTAGENESIS 109 



ultimately give rise at least to a mottled plaque, because sometimes 

 that copy of that original DNA will have made a mistake. But he 

 would suggest that that original ethylated guanine cannot persist as 

 such in that original maternal molecule. He never suggested that ethyl 

 guanine ever replicates after two cycles, so you again get an ethylated 

 guanine. That is what you are denying. 



Zamenhof: No, I am not denying anything he said. On the contrary, 

 I am trying to amplify it. We realize now how complex the mutation 

 process may be. It is a multistep process. In the first step, alkylation 

 occurs. In the second step, DNA may lose purines. In the third and 

 final step, which is finally accepted, the wrong purine gets there to fill 

 the gap. I'm just trying to amplify that the process of mutation may 

 be a very complex, multistep process. 



Auerbach: Does Dr. Zamenhof think that all the alkylating agents 

 act at the 7-position? 



Zamenhof: No, I didn't say that. But I am sure that none of the 

 alkylating agents, especially mustard, can be accepted as such during 

 the replication of alkylated DNA. 



Auerbach: Oh, no, no! But it is always the guanine group which is 

 attacked in DNA? 



Zamenhof: We have evidence that it is predominantly guanine 

 (60). 



Lederberg: Let's clarify the remark, for the record, that the alkylat- 

 ing group must come off. I think what you mean is that it cannot be re- 

 produced as such in further copies of that DNA. 



Zamenhof: Yes, that's right. 



Lederberg : That does not mean, as a chemical entity, the alkylated 

 nucleotide may not persist as such as long as that original DNA 

 molecule persists. 



Zamenhof : Correct. 



Neel: Could you show us the difference between one-armed, two- 

 armed, and three-armed mustard? 



Auerbach: Well, the nitrogen mustard that is most frequently used 

 has two chloroethyl groups. There is also one with only one chloro- 

 ethyl group, but this is a rather weak mutagen. Ethylene oxide is 

 one-armed, and so is ethylene imine. Two ethylene oxides linked 

 together give the two-armed diepoxybutane. TEM has three groups 

 of ethylene imine and is three-armed. The cancer research workers 

 find that only two-armed or three-armed compounds are carcinostatic, 

 but for mutagenic action this simply is not true. There is not the 



