HOWARD B. NEWCOMBE 



cells) since this could not have occurred without a noticeable change from 

 the 50 per cent survival. 



It is conceivable, of course, that in a suspension of multinucleate strands 

 the shape of the dose-mutation curve might be influenced by factors other 

 than those operating in the uninucleate spores. However, the direction 

 and extent of the deviation from a linear response are very similar in uni- 

 nucleate spores, binucleate spores, and 8-nucleate strands ; and the evidence 

 against a selective killing of cells which would otherwise give rise to induced 

 mutant colonies, is likewise consistent throughout. 



Table II. — Effect of pre-incubation on the consequences of doubling the dose of X-rays 



A non-linear mutagenic response to the second irradiation, in the absence of altered survival 



(Dose : x = 8,000r. Incubation in medium) 



Growth : no nuclear division at 4 hours ; spores mostly binucleate at 6 hours ; approxi- 

 mately 8-nucleate strands at 8 hours. 



Controls : as in previous table. 



Note : All incubations carried out in closed metal boxes with little or no air-space above 

 suspensions. 



The non-linearity might perhaps be accounted for in terms of a grossly 

 heterogeneous population, but we would have to make some very improbable 

 assumptions : not only that the part of the population which resists killing 

 consists of two fractions (one mutation-resistant and one mutation-sensitive), 

 but also that the difference between resistance and sensitivity is extreme 

 with respect both to killing and to induced mutation, and that intermediate 

 degrees of resistance are virtually absent. 



Since a differential killing of induced mutants can be ruled out, and an 

 interpretation in terms of a population heterogeneity is only remotely 

 possible, it seems probable that high doses of radiation saturate (or otherwise 

 interfere with) some essentially intracellular response on which most of the 

 induced mutation, and apparently a part of the killing, depend. 



329 



