202 MUTATIONS 



of the Oklahoma Academy of Sciences (14), had also reported that 

 ascorbic acid was mutagenic in micrococcus (twelve times in the strep- 

 tomycin marker and up to 300 times in the penicillin marker). 



Ascorbic acid by itself is not a very important or very interesting 

 mutagenic agent. It is auto-oxidizing and, while doing so, may produce 

 some free radicals. Its action may be similar to that of ferrous iron. 

 But what is interesting is the ubiquity of ascorbic acid. The presence 

 of ascorbic acid in some cells has been reported, and although it has 

 not been proved that ascorbic acid ever comes in contact with the 

 DNA of these cells, it is possible that their life is impossible without 

 ascorbic acid. 



Using the phrase of Dr. Dobzhansky, that mutations are the only 

 known raw materials of evolution, we may say that here we have a 

 built-in evolution, that is, evolution inseparable from the cell. 



This is merely to start a possible discussion on the very important 

 subject of normal intracellular chemical mutagens, which act in addi- 

 tion to mutagens provided from the outside. 



There are practically no publications on this subject except for 

 Novick and Szilard's findings that adenine, which may be a normal 

 component of the cell, is mutagenic (44). 



After Dr. Goldstein's presentation, it came to my mind that glyceral- 

 dehyde, which is a normal component of the normal glycolytic cycle, 

 may also be mutagenic if acetaldehyde is. Of course, the efficiency of 

 aldehyde as a mutagenic agent will probably decrease as the chain 

 length increases, but the glyceraldehyde is always with us and we have 

 to take it into consideration. Perhaps, someone in the audience may 

 suggest some other such substances of potential significance, which 

 may contribute to the total so-called spontaneous mutation rate. 



Goldstein: One class of drugs that is widely used is the barbiturates, 

 which are pyrimidine analogues. We did some experiments recently, 

 using T4-resistance in E. coli B to see if it was mutagenic, and Dr. 

 Novick tells me that he also had done a similar experiment. Our experi- 

 ment was with pentobarbital, one of the most frequently used hypnotic 

 agents, at concentrations of 150 mg/1, which is the same as caffeine in 

 Dr. Novick's experiments. This was not mutagenic at all under the 

 same conditions in which caffeine was mutagenic. Incidentally, in our 

 system caffeine was not nearly so mutagenic as in Novick's T5-resist- 

 ance system. It increased the frequency of spontaneous mutants only 

 some two to threefold. 



Novick: One very important thing here, if I may interject, is the 

 technique used to measure mutation rate. Before I would take such 



