MANNER OF PRODUCTION OF MUTATIONS 537 



apply to mutagenesis, that this process, acting against mutagenesis and 

 perhaps initiated, in part at least, even by the radiation of mutagenic 

 wave length, might play an important part in the decline in mutagenic 

 efficiency of ultraviolet with increasing dose. Evidence apparently sup- 

 porting this idea was obtained soon afterward, in work of Haas et al. 

 (1950) on Micrococcus ( = Staphylococcus) aureus,,\vhich proved that ultra- 

 violet, when acting indirectly through the medium, does at higher doses 

 tend to destroy or inactivate the very mutagenic substances which it 

 itself, at lower doses, has produced. Unfortunately, however, the range 

 of wave lengths of the ultraviolet used in these particular experiments is 

 not stated so that it is conceivable that only ultraviolet of nonmutagenic 

 activity was reparative. 



Because of the decline in slope of the frequency-dosage curve for point 

 mutations produced by ultraviolet, regardless of its cause, it has not been 

 possible, in the experiments discussed, to be sure that the primar}^ muta- 

 tional events bear a really linear relation to dose. The appearance of a 

 straight-line relation at the lower doses might merely be a result of the 

 curve changing from concave to convex in this rather limited dosage 

 range. That is, at still lower doses, for which it is difficult to obtain 

 sufficiently accurate determinations of the mutation freciuency, the curve 

 may actually be rising at an accelerating rate as a result of the mutations 

 being two- or multihit effects. Certain results obtained by treatment of 

 Drosophila pole cells, by Altenburg, Altenburg, and Baker (1952) strongly 

 point in this direction, yet the data do not seem sufficiently extensive, 

 considering the experimental and statistical deviations to which this type 

 of work is subject, to prove the point definitely. Data published by 

 Swanson (1952) on the frequency of mutations induced by ultraviolet in 

 Aspergillus spores also show a concavely rising curve at low doses. 



The results of Novick and Szilard (1949) on mutations induced by 

 ultraviolet in Escherichia coli, which give no evidence of change in the 

 characteristics of the curve at higher doses, show a frequency which, 

 throughout the rather wide range of doses used, varies with a power of 

 the dose a little higher than 2, as though two to three hits were usually 

 necessary for a mutation. However, it might be postulated that, in this 

 material in which genetic analysis by crossing is excluded, there is a 

 diploid condition of the organisms, necessitating a coincidence of two 

 mutations, one in each allelic locus, or that a combination of two or more 

 mutations at different loci is usually necessary for the given observable 

 effects. Similarly, in a " histidineless " stock of E. coli, which has 

 unusually long cells, Kaplan (1950b) found that back mutations to 

 histidine independence arise with a frequency dependent on a power of 

 the dose higher than 1. This corresponded with the fact that the rate 

 of killing also depended on a high power of the dose in this stock, whereas 

 in his stock B, having smaller cells, the killing depended on the first 



