188 MUTATIONS 



Freese: I propose that one should test with tissue cultures the in- 

 duction of point mutations, because I think the mistake has been made 

 in the past that, merely because one could more easily detect larger 

 alterations of chromosomes, these mutations have been examined more 

 carefully. I think that there may be dangerous mutagens that are given 

 as drugs or used as food. These agents are chemically unreactive and 

 therefore expected to produce only small changes of the genetic 

 material. 



Neel: Can we go back to the question that Dr. Goldstein raised, 

 which really hasn't been answered? What mammalian or nonmamma- 

 lian system or combination of systems would be the best screening 

 device for the mutagenicity of this whole series of compounds? Isn't 

 this actually your question? 



Atwood: I think we have agreed that none would be entirely satis- 

 factory. However, they might be suggestive. 



Goldstein: There were really two aspects of the question. One was 

 whether any screening system in nonhuman systems would be of any 

 predictive use at all, and, secondly, whether a screening system based 

 on human cells would be useful. If one could determine the relative 

 mutagenicity of a series of drugs, then certain practical things could 

 be done about it. I think we can assume that for most drugs the relative 

 mutagenicity will be unrelated to the nature of the drug action. There 

 is almost always a variety of drugs with similar actions, and which one 

 is chosen now usually depends upon competitive promotional efforts, 

 patent situations, tradition, cost, and so on. 



To give you a specific example of this, there is a substance very 

 closely related to caffeine, namely, trimethyl uric acid. In screening 

 tests that showed up caffeine as a chromosome breaker on certain plant 

 systems, this compound was not (32) . We do not know whether tri- 

 methyl uric acid has a similar stimulant effect on the brain to that of 

 caffeine. Suppose it does. Then one obviously would choose that drug 

 which had the desired pharmacologic action, but did not have the 

 mutagenic capability. There may be similar examples. 



Novick: May I point out the danger of that kind of argument? I 

 did test tetramethyl uric acid, and I did find it was nearly as mutagenic 

 as caffeine; in fact, it was worse, because the effect of caffeine can be 

 counteracted by adenosine or by growth under anaerobic conditions, 

 while that of tetramethyl uric acid is not counteracted very much 

 under these conditions. I think the only conclusion, to answer your 

 earlier question, is to use a wider range of screening techniques. 



All we can do is form a basis for suspicion, so that people who finally 



