MUTAGENESIS 113 



The question is, how can one explain this? I will first give a theoret- 

 ical explanation, and then an experimental result. The theory is that 

 when you attach the alkyl group, either the ethyl or the methyl, at the 

 7-position, you get the positive charge in the ring, but the more elec- 

 trons this alkyl group can provide to the ring the smaller the positive 

 charge will be. 



It is known from chemistry that the methyl group is the better 

 electron donor than the ethyl group. This should make the ring less 

 positive, and therefore the likelihood that a group breaks loose is less. 



Actually, Zamenhof, in his first paper, could observe the methylation 

 of these bases, but he had difficulty in finding any ethylation. I think 

 that this is automatically explained because the methyl groups are 

 more stable than the ethyl groups. 



The experimental part is that we treated deoxyguanosine with 

 diethyl sulfate and with dimethyl sulfate, and then determined in the 

 fraction collector the relative amounts of guanine, methyl guanine, and 

 methyl deoxyguanosine and similarly for ethylation. 



I don't want to go into the details of the calculation, but we found 

 that the probabilitj' of decay of a methylated guanine is of the order of 

 five times less frequent that the probability for an cthylated guanine; 

 this is in agreement with both the theoretical expectations and the ob- 

 servations about mutagenicity. 



Auerbach: There is one group of chemical mutagens which I should 

 mention, although I don't think they have been tried on phages. Those 

 are mutagens which perhaps chemically have the best claim to being 

 called radiomimetic. This is a very loose term which is used often for 

 mutagenic chemicals. 



There is one group of mutagens to which, possibly, this term applies 

 at the chemical level — the peroxides. Hydrogen peroxide is a weak 

 mutagen, but it can be definitely mutagenic, at least under conditions 

 where it is not destroyed at once. It is not mutagenic for Drosophila. 

 Apparently it is destroyed at once by catalase. It is weakly mutagenic 

 for bacteria. But various organic peroxides have been found to be good 

 mutagens in Neurospora as well as in Drosophila. 



Now, how does this link up with radiation mutagenesis? There is a 

 lot of discussion as to how far radiation produces its effect indirectly 

 via water radicals, including their combination to hydrogen peroxide. 

 I think that the extent to which this happens is still very doubtful. The 

 pendulum seems to swing back again toward attributing more im- 

 portance to the direct effect on the target molecules. But there cer- 

 tainly is one case, well authenticated, where radiation mutagenesis acts 



