STRAUSS." DISCUSSION OF SESSION II 175 



Consider the behavior of bacteriophage treated with ethyl 

 methanesulfonate. Although phage treated in vitro produce mutants 

 when used to infect bacteria, such treated phage are not yet mutant. 

 Single bursts yield groups with a few mutants and others with many, 

 indicating that the "mutation" may occur at any time during the 

 replication of the treated DNA (9). 



Our present ideas require that a mutation represent a change 

 in base order within the genetic DNA. All mutagens must lead to 

 such a changed base order. If this hypothesis is accepted, the prob- 

 lem becomes a determination of how each particular mutagen may 

 bring about a change. It is not required, for example, that a chem- 

 ical mutagen react directly with DNA. As Szybalski (15) has shown, 

 the alkylating agent triethylene melamine may react with pyri- 

 midines and pyrimidine derivatives to give products which are 

 in turn incorporated into the DNA where they behave as analogues 

 leading to an increased mutation frequency. It must not be sup- 

 posed that mutations need represent changes in only single nucle- 

 otide pairs. Freese (1) points out that the class of mutations he 

 calls transversions may represent merely the change of a purine 

 for a pyrimidine base. A transversion may also result in a more 

 extensive change in the genetic material since incorporation of a 

 purine at a pyrimidine site could result in sufficient deformation of 

 the double helix of DNA to allow for the substitution of other 

 bases. Fresco and Alberts (2) have shown how noncomplementary 

 bases can be accomodated in a helix by the formation of loops com- 

 ing out of the helix. Such loops might, on DNA duplication, result 

 in the addition or deletion of portions of the nucleotide chain. It 

 is important to realize that current ideas of mutation as a result of 

 base substitution are not so restrictive that they require all muta- 

 tions to be simple changes in single base pairs. 



It is also essential to emphasize that the mutagenic agents, 

 particularly the reactive mutagenic alkylating agents, may have 

 several different reactive sites within the organism and that their 

 reaction, even at a single site, may have both mutagenic and non- 

 mutagenic consequences. The alkylating agent diethyl sulfate (ethyl 

 sulfate) not only is mutagenic but also produces a permeability 

 change in the bacterial cell which makes magnesium ion more 

 available to chelation and removal by citrate (13). Many alkylating 



