264 PETER ALEXANDER AND MISS D. I, CONNELL 



after the exposure followed by incomplete repair of the organ as a whole. Ethyl methane 

 svilphonate differs from the other agents in not producing this massive destruction but 

 is a po^^•erful mutagen in all systems. 



MAisiN: It would be interesting to know the effect of your fractionated irradiation on lung 

 tumour induction. 



ALEXANDER: Under our irradiation conditions few tumours were induced in the CBA mice. 

 MAISIN: But much more than Dr. Upton reported yesterday? 



ALEXANDER: No. We had 23% animals dying with malignant tumours in the controls and 

 38% in the irradiated. This difference is unlikely to be significant. Our data are in agree- 

 ment with Dr. Mole's observations reported yesterday. Using the same strain of mice he 

 found that, after large doses of X-rays, no leukaemia was produced wlule smaller doses 

 gave rise to a large incidence. 

 kotblat: I think you have more than one tumour in some of the mice. 



ALEXANDER: YeS. 



MAISIN: If you irradiate one lung only instead of the whole animal you may get much more 



lung cancer m your mice than with total-body irradiation. Because irradiating the lung 



only in rats gave us 70% of lung tumours, possibly because the animal's life is not 



shortened and it survives long enough to have these tumoiu-s. 



berenblum: In the series with ethyl methane sulphonate the life of the animals was not 



shortened and yet tliis compound was very highly carcinogenic. Does that mean that 



most of the tumoiu-s appeared very late m life? 



ALEXANDER: We Started kUlitig them off at about 700 days because we reahzed that there 



was this high tumour mcidence and we wanted to make sure of the histology of the 



tumours. We don't know whether these lung tumours grow very slowly or whether they 



only appear late in life. You see with no Ufe-span shortening we had virtually no dead 



mice until about 600 or so days. 



berenblum: But you must have started killing them off in large numbers at the end 



because your figures don't refer to the age at the end of the experiment but to the age of 



the 50% of the survivors, 



ALEXANDER: Ycs. As soon as we felt confident that it hadn't produced any life-span 



shortening we thought we would use the same animals to give us information about the 



carcinogenicity of ethyl methane sulphonate. We were so puzzled by the fact that 



myleran and clilorambucil which are carcinogenic under other situations were not 



carcinogenic when given in three large doses by mouth. It has been suggested that this 



absence of carcinogenicity arose because it was given by mouth. But this now seems 



unlikely because the monofunctional agent also given by mouth did produce tumours. 



muller: Were those medians or averages of life-span? 



ALEXANDER: Median, in time at which 50% of the animals were dead. 



lajierton: Dr. Alexander said it was very carcinogenic but it looked as though the whole 



of the excess was in the lung adenomas and kidney tumours. 



ALEXANDER: They weren't aU lung adenomas. About half were carcinomas. Kidney 



tumours might well have been metastases from the lung. 



lamerton: Does this correspond to the normal spontaneous distribution of tumours? 



ALEXANDER: Yes; in control animals about 25% show lung tumours at death (see my 



other paper, p. 281). 



LAMERTON: I wonder if the fact that you had jout excess in kidney and lung only meant 



that the agent didn't actually get around. 



ALEXANDER: I don't know whether I believe this a vaUd argument — carcinogenic 



compounds have odd predilections for site of action and these are usually unrelated to 



distribution. I see no reason why such a small compound shouldn't get around and 



