214 MUTATIONS 



Freese: I'm just mentioning this because by understanding the 

 metabolism first, one may be able to realize the difference or 

 similarity between humans and bacteria. 



Goldstein: It would be a great mistake if the statement stands in 

 the record that caffeine is metabolized so fast that we don't have to 

 worry about it. The fact is there is a very large and significant amount 

 of caffeine present, on an average basis, continually, and this amounts 

 to approximately 1 per cent of the amount that was shown in Dr 

 Novick's experiments to be mutagenic. 



The final problem I should like to attack is this: Is it possible to 

 extrapolate from the known mutagenic effects of caffeine in bacteria 

 and in Drosophila, to obtain any kind of quantitative estimate of the 

 potential genetic hazard of this drug in man? I don't think these 

 calculations will be worth very much because in order to make them at 

 all one has first to make a number of assumptions, any one of which 

 might be quite false. Nevertheless, with tongue in cheek, I am going to 

 proceed. 



To begin with, I assume the following: (1) Caffeine mutagenesis, 

 directly or indirectly, is an effect upon DNA. (2) The average 

 susceptibility of DNA to caffeine mutagenesis is about the same in 

 all species. (3) All genes of a given organism are equally susceptible 

 to caffeine mutagenesis, or, if not, considering the large number of 

 genes in an organism, one can at least speak meaningfully of an aver- 

 age susceptibility. (4) Caffeine mutagenesis is a linear function of dose. 

 (5) Caffeine equilibrates freely between plasma and gonadal tissue 

 and passes freely into the fetus throughout the gestation period. (6a) 

 Caffeine acts continuously upon DNA, regardless of stage in the replica- 

 tion cycle, so the total effect is linear with astronomical time, or 

 alternatively, (6b) Caffeine acts only during DNA replication, so the 

 total effect is proportional to biological time (the number of replica- 

 tion cycles) . 



Novick: I would like to challenge one. Are you going to discuss 

 them? 



Goldstein: Let's discuss them now. I am making the assumption that 

 caffeine mutagenesis has something to do with DNA, whether it acts 

 on DNA itself, DNA replication, or some other cell process concerned 

 with replication. 



Benzer: It is a highly unwarranted assumption. 



Goldstein: It's not really a necessary assumption to what we're 

 talking about. 



Benzer: Then, let's just cross it out. 



