496 MUTATION AND PLANT BREEDING 



interpretations of the actions of mutagens. She lamented the cur- 

 rent tendency to assume as a working hypothesis that most muta- 

 genic action involves a direct chemical relation between the mutagen 

 and DNA. Yet in the phages, where the DNA structure is pre- 

 sumably simple and not closely bound with protein, and in the 

 bacteria also where mutant effects can be defined in specific chem- 

 ical terms, the hypothesis has proved extraordinarily fruitful — as 

 Smith has shown in his excellent review. 



The "Freeseian" transitions, involving substitutions of the 

 normal purine and pyrimidine bases by specific analogs, provide 

 satisfying interpretations — even if still theoretical — of the experi- 

 mental data. The natural extension of the concept is that any agent 

 which can interact with normal cell constituents to produce base 

 analogs is a potential mutagen. It does not follow necessarily that 

 the in vivo induction and incorporation of base analogs is a simple 

 process, though it is tempting to assume so in the case of nitrous 

 acid (on the basis of in vitro evidence). Among alkylating agents, 

 the evidence that dimethyl sulfate and tri-ethylene melamine react 

 preferentially, with purines and pyrimidines respectively, suggests 

 that some of their mutagenic activity may involve the production 

 of base analogs in vivo, but there is no reason to suppose that this 

 is their sole mode of action. 



There are other and cruder ways of disturbing nucleotide 

 sequences in DNA than by stepwise substitution of individual bases 

 followed by miscopying, and these may involve a variety of meta- 

 bolic pathways. Even when individual base analog substitution is 

 a plausible mechanism, the pathway may be rather indirect. In 

 bacteria, as Haas has reported in this symposium, a number of steps 

 lead from the primary effects of UV irradiation to the phenotypic 

 expression of the mutant. Preincubation with the bases normally 

 present in RNA (adenine, guanine, cytosine, and uracil) increased 

 the subsequent mutation rate with UV. Substituting the RNA base 

 uracil by the DNA base thymine in the media reduced the muta- 

 tion rate considerably. Each step in the pathway leading from 

 mutant induction to phenotypic expression could be blocked by 

 specific changes in the internal or external "environment" of the 

 organism. If his interpretation- — or my understanding of it — • is cor- 

 rect, the potential mutant or precursor has first to be stabilized by 



