MECHANISMS OF LIFE-SPAN SHORTENING 245 



could stand having it missing they could surely stand having an extra one. We know that 



polyploids can exist too, and as soon as you have a polyploid you have much more 



lability because then the loss or addition of one or two chromosomes isn't proportionately 



nearly as much of a change as it is to a diploid. Therefore I think there's a lability in this 



respect but that what the cells can't stand is the loss of any portion of both members of a 



pair of cliromosomes, or of one chromosome that's only present in haploid. 



bacq: In that case one would suspect that poljrploids would increase regularly with 



resistance. 



MTJLLER: Oh, yes. 



bacq: And apparently I had stated that in the book written with Peter Alexander, it 



seems not to be true in yeast. 



MTJLLER: I think that can be understood in the light of the two different mechanisms 



which I spoke of by which chromosome breakage can kill the daughter or descendant 



ceUs. That is, where you have polyploidy giving you greater radiation sensitivity the 



deaths are presumably caused by the cliromosome bridges. Now m Drosophila we have 



some evidence that occasionally even in the later stages when certain special cliromosomes 



are present their bridges kill the cells, since the presence of one of these chromosomes will 



cause radiation sensitivity even in heterozygotes. 



We have therefore the foUowmg seriation: the haploid, which is ordinarily expected 

 to be the most sensitive; the diploid, which is much less sensitive, if the species is one in 

 which the chromosomes usually don't form lethal bridges but are lost completely. But if 

 you have a certain proportion — let us say 10% of the breakages — followed by lethal 

 bridges, that wouldn't be enough to play a big role in the case of the haploid, nor even in 

 the case of the diploid. But when you go from the diploid to the triploid or the tetraploid 

 then you have loss of both or aU members of the same type of cliromosome — hjrpoploidy 

 — playing very little role, and now it's the bridges that become more and more damaging 

 as the ploidy increases. And I think your cases correspond with this situation. 

 ROTBLAT: You Say that there is a fundamental difference in the process of radiation- 

 induced life-shortening and natural senescence and natural mutation. Is the loss of cells a 

 sufficient explanation? 



muller: I should think it would be. I thuik the matter should certainly be explored with 

 this question in view. In our work with Drosophila, anyway (and that's the only thing 

 I have a first-hand experience with in this connection), the radiation-mduced Life-span 

 shortening so closely follows what must be the loss of ceUs that very httle of it can in that 

 case be due to impairment of cells short of their loss. Now in the case of natural life-span 

 shortening I wouldn't know if this held but I would think it very unlikely that in natural 

 senescence the loss of cells resulted from genetic changes occurring in them. There might 

 be some other reason for it — some physiological agemg of a totally different kind. And 

 yet the S3Tnptoms might be very similar. The cells are lost here and there in a scattered 

 fasliion — more and more of them. 



