GENERAL DISCUSSION 349 



largely a result of bone-marrow damage — should not one then expect a very pronounced 

 sex difference? 



muller: Not so pronounced a sex difference. When we did some figuring with this we 

 found that the male and female — and the tests showed it too — were somewhat more alike- 

 than we had offhand judged that they should be. In the caseof a mammal, the X-chromo- 

 some material is a much smaller part of the chromosome mass than it is in Drosophila. 

 Moreover, you must remember this — that just where your curve will lie in any given case 

 depends on other factors too, because with a given genotype and given environmental 

 conditions an individual might be killed by a smaller number of cell-deaths than under 

 other conditions, and even the sex difference might in itself influence thmgs. 

 ALEXANDER: But if one could culture female and male cells in vitro then one would expect 

 a real difference. May I take this one step further. If one did have two bottles fuU of cells 

 which have been cultured from male and female animals of the same strain, and one then 

 measured their direct dose: resj)onse curve to cell killing, clone formation or sometliing 

 like that — would you then agree that if there was no great difference between the two, 

 that this would indicate that claromosome breakage was not a major factor contributing 

 to cell death? 



MULLER: As you may remember, I did conclude that chromosome loss by breakage, 

 giving hypoploidy, was probably not the main cause of death when Drosophila embryos 

 were irradiated. However, I don't yet feel certain that chromosome breakage was not the 

 cause of death since in some cells, death may be caused by chromosome bridges resulting 

 from the breaks, and this influence works the other way than ordinary cliromosome loss, 

 being positively correlated with degree of ploidy. If that is the case then at a certain 

 stage the two mechanisms of mortality by chromosome breakage might balance one 

 another. There is in fact evidence by Clark and others that in the very early embryo of 

 Hahrohracon the mortahty is positively correlated with degree of ploidy. One has to look 

 out for all sorts of comphcations like that. 



UPTON: I know very little about the PG chromosome, and I wondered whether experi- 

 ments might be done with mice havmg such translocations in an effort to investigate 

 the influence of ploidy — the total cln-omosomal length so to speak? 

 MULLER: Investigations along these Lines certainly need to be carried out on vertebrates. 

 As long ago as 1941, 1 apphed for a grant to study the influence of ploidy in salamanders 

 on the amount of radiation damage, as measured by effects on growth and regeneration, 

 carcinogenesis, etc. But the organization to which I appUed, led by Peyton Rous, had a 

 quite different viewpoint on such matters. Such studies can stiU be done with salamanders 

 and was there not some report from Sweden of triploid rabbits or has this been dis- 

 credited? At any rate, the material for work of tliis type is now becoming richer. 



Systems for Carcinogenesis Studies 



BACQ: Thanlc you, Dr. Muller. I thmk we might now proceed to a further question. I 

 would take for a start a remark by Prof. Lamerton who said that bone was not a satis- 

 factory system to work with in carcinogenesis. We have seen that skin also has many 

 obvious diflficulties. Now I put the question, what kuid of system might be better? 

 Leukaemia in mice is a peculiar system because viruses are likely to be a major problem 

 in this type of carcinogenesis. Can it be compared with others? Prof. Lamerton, would 

 you make some comments on this? 



LAMERTON: One of the difficulties of using bone in carcinogenesis studies is, of course, that 

 its radiation response is so very complex because of the many different types of cell 

 present quite apart from the change with age, and other factors, of proliferation patterns. 



