98 MUTATIONS 



hypoxyanthine deoxyniicleoside triphosphate is not made in a bac- 

 terium, so you don't find any inosine in DNA. 



Auerbach: Is there any theory to account for the mutagenic effect 

 of compounds that are not incorporated? 



Freese: I think most clearcut is the observation for azaserine, which 

 we know interferes with the purine synthesis; caffeine probably does 

 the same. Thus it may be that their mutagenic effect is due to the 

 distortion of the normal purine metabolism; for example, due to an 

 abnormal ratio of adenine and guanine DNA precursors. 



Auerbach: That would explain the antimutagenic effect of adenosine 

 riboside. 



Freese: Yes, that would explain the antimutagenic effect at the same 

 time. Now the difficulty is that some experiments have been done, I 

 think by Magazanik, where they have tried to influence the direct 

 DNA precursor pool by adding a purine analogue or by using mutants, 

 and, to their surprise, they found that whenever you have a condition 

 under which the DNA can duplicate, you find approximately the same 

 ratio for guanine and adenine as you find in normal cells. 



Auerbach: This is also true for caffeine. However, when 8-ethoxy- 

 caffeine breaks chromosomes, it docs so at a stage when DNA replica- 

 tion is already finished. 



Freese: Is that proven? 



Auerbach: Well, Kihlman (40) found it. 



Freese: There is the possibility that the bulk of the DNA duplicates 

 at a certain time and a few DNA linkages are made later, and that is 

 sufficient — 



Auerbach: No, at the end of interphase in plants, where I think the 

 DNA is— 



Freese: Then, in some cases, you have new DNA synthesis already, 

 so I think one has to examine this very carefully. 



Auerbach: The antimutagenic effect of purine ribosides was very 

 weak in Kihlman's (41) experiments. He had some, but very little, not 

 comparable at all with Novick's experiments. 



Zamenhoj: I would like to discuss in a few words another mutagen 

 — which is new because it is so old that it became unfashionable — 

 deuterium. 



Something like seventeen years ago, with Dr. Demerec, we studied 

 mutagenicity of heavy water in Drosophila (89) and did not find any. 

 But now the techniques of microbial genetics have progressed so far 

 that we thought this should be reinvestigated. Miss De Giovanni in 

 our laboratory has now found that deuterium oxide is mutagenic (12, 



