MECHANISMS OF MUTATION PRODUCTION IN MICRO-ORGANISMS 



However it is quite certain that the mutabiUty of individual nuclei must 

 have been reduced to about one half in the experiments using nitrogen 

 treated uninucleate (and binucleate) spores. And it must also be that the 

 sensitivity of the individual nuclei to induced mutation is at least doubled 

 in the binucleate cells arising under normal conditions of growth. 



Thus physiological differences are capable of resulting in very considerable 

 variations in sensitivity to induced mutation. And furthermore, in the 

 experiments demonstrating this, lethality and mutagenesis were similarly 

 affected, indicating that the modifiable processes are in part common to 

 both types of response. 



CONCLUSIONS 



Originally it was hoped that these experiments would yield information 

 regarding the time of the induced mutations, and whether such changes 

 were in any way dependent on the process of gene (and chromosome) 

 replication. Both X-ray and ultraviolet induced mutations had appeared 

 to be delayed until the time of gene replication in Escherichia coli, since 

 irradiated cells gave rise to colonies sectored for induced changes, even 

 where the so-called ' double selection ' technique had been used in an attempt 

 to insure that each colony came from a single irradiated gene complement 

 (Newcombe"' ^ ; WiTKiN^). Also, the mutagenic effects of ultraviolet in 

 Streptomyces had been found to lose their capacity for photoreversal only under 

 conditions favourable to nuclear division, and at a time shortly before the 

 nucleus becomes visibly double (reported elsewhere). 



However, we have not been able to add to these observations any evidence 

 of a critical period in the nuclear division cycle during which mutation 

 might be taking place. Exceptional sensitivity to induced mutation appears 

 to extend over the whole of the binucleate stage, and not just a part of it ; 

 and the fractionation experiments appear to indicate that nuclear division 

 brings no release from an earlier saturation (or impairment) of the capacity 

 for induced mutation. 



What has been shown is that the physiological state of a cell at the time 

 of irradiation can influence the likelihood that it will subsequently develop 

 into a mutant colony. Where the cells are multinucleate at the time of 

 irradiation it is not entirely certain whether such differences might not arise 

 through effects influencing subsequent competition between mutant and 

 non-mutant nuclei within the strands. However, where only one or two 

 nuclei are present it is clear that the sensitivity of individual nuclei to induced 

 mutation is subject to very considerable physiological control. 



This suggests the possibility that the non-linear dose-response relation- 

 ships may also be physiological in origin. In support of this view, examples 

 of non-linearity have been described which could not be the result of 

 differential killing of induced mutants, and which would be very difficult 

 to explain in terms of an initial population heterogeneity. 



In view of the evidence for a physiological control over the response of 

 the genetic material of Strepto?nyces to mutagenic agents, it seems altogether 

 possible that the physiological changes produced by high doses of the 

 mutagens themselves may be effective in altering the capacity to respond 

 to a further exposure. 



338 



