MUTATION AND PHENOTYPIC VARIATION IN PHAGES 311 



Irradiation during the later two thirds of the latent period gave 

 a marked increase in the frequency of mutations. The fre- 

 quency was dose-dependent with a threshold of 3,000 ergs per 

 square mm. and a maximum between 5,000 and 6,000 ergs. 

 The maximum frequencies observed were in the range from 100 

 to 200 X 10"'^ to give about a 10-fold increase over the controls. 

 The radiation dose was in the same range as that found to be 

 mutagenic for the host bacterium (Demerec and Latarjet, 1946). 

 Phage T2 and T2^ were equally susceptible to ultraviolet in- 

 activation when either extra- or intracellular, but apparently no 

 experiments were done with mixedly infected bacteria to rule out 

 the possibility of selection under these conditions. The actual 

 yield of mutants may well have been higher than observed in 

 these experiments because of the probability that some mutant 

 particles were lost because phenotypic mixing prevented their 

 plating on B/2. In later experiments (Latarjet, 1954) in which 

 phenotypic mixing was eliminated by passage of phage progeny 

 through strain B before plating on B/2, the frequency of mutant 

 particles was raised to 37 times that of unirradiated controls. 



The effect of the mutagenic agent, nitrogen mustard, on phage 

 T2 was studied by Silvestri (1949). The agent caused exponen- 

 tial inactivation of phage that was not stopped by dilution into 

 reagents that destroyed nitrogen mustard, but apparently was 

 arrested by adsorption of the phage to susceptible host cells. 

 The rate of inactivation was proportional to the concentration 

 of the mustard. The adsorption of the treated phage particles 

 to strain B, followed by plating of infected bacteria on B/2, 

 revealed a large increase in the frequency of host range mutants 

 among the survivors. The frequency increased from 5 X 10"^ 

 in the controls to 10"^ in Af/20 mustard and lO"'' in Af/10 

 mustard. The increase in frequency was parallel to the de- 

 crease in survival so that a selective effect could be invoked 

 only if the mustard had no effect at all on mutant particles. 

 The most reasonable explanation of the increased frequency of 

 mutants is a direct mutagenic effect of the nitrogen mustard. 

 Although the agent is applied to the phage before infection, 



