Discussion 71 



Alper: Yes, the phage DNA, but I am talking about the actual 

 biological continuity of the phage particle as such. Now you are talking 

 about these threads presumably as carriers of the genetic material. 

 What is supposed to happen when phage gets into a bacterium is that 

 the genetic components come apart and they are somehow reconstituted. 



Spiegelman: I don't think that is true. 



Alper: I think it is. 



Mitchell: I would like to make a suggestion about the therapeutic 

 action of radiation (see Mitchell, J. S. (1956), J. Colloid Sci., in press). 

 It is well known that a dose of say 2,250 r of gamma-rays produces 

 permanent healing of a typical small carcinoma of the skin in man. The 

 DNA content per nucleus in such a tumour was found by u.v. photo- 

 micrographic absorption methods to be 7-8 X 10'^^ g. The mean dia- 

 meter of the tumour cell nuclei was 6-86 microns. The number of ion 

 pairs within the material of the nuclei thus corresponds to a number of 

 DNA molecules of arithmetic mean molecular weight almost exactly 

 7 millions. This may suggest inhibition of reduplication, but that 

 hypothesis is not essential to the argument. While classical target 

 theory is obviously not the mechanism involved, one must think of a 

 macromolecular lesion of DNA or DNA-protein as the basis for the 

 therapeutic effect. 



A possible experimental test is that one factor in radiosensitivity 

 would be the molecular weight of the DNA within the cell. I have 

 already started by methyl-green staining of sections cut in the same 

 block from radio-curable and radio-incurable tumours of the uterine 

 cervix. In the first pair of specimens there was very much less intense 

 methyl-green staining in the radio-incurable case. Aluch further work is 

 required. 



Lajtha: I should like to ask Prof. Butler three questions, the first one 

 being whether he thinks that DNA in the cell may be more radioresis- 

 tant than DNA in solution. We labelled bone marrow cells in vitro with 

 ^*C-adenine and then irradiated with 500 r and followed whether up to 

 48 hours there was any loss of labelled DNA; we found no loss after 

 500 r. We have repeated the experiment using 5,000 r, not with labelling 

 but just following the staining reaction of these cells with methyl 

 green-pyronin and Feulgen, and were unable to detect any significant 

 decrease in stainability. I don't tnink our technique is very sensitive, so 

 there may have been soine small losses not detectable, but certainly no 

 significant loss. 



Secondly, how can one explain the differential radiosensitivity of the 

 incorporation of i*C-formate into DNA on the hydrogen bond breakage 

 theory ? Thirdly, what does Prof. Butler think is the mechanism of the 

 indirect radiation effects on bone marrow when the spleen is irradiated ? 

 Butler: As to the first question, that is really a type of chemical 

 experiment and you would picture it as similar to a test-tube experiment 

 in which one observed the liberation of adenine. 

 Lajtha: Yes. 



Butler: I think it would require more than 5,000 r to produce any 

 observable effect. 



