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DISCUSSION 



CURTIS: You showed that radiation can have an initiating action. Have you reversed this 

 process using croton oil as an initiator and then foUowmg with radiation? 

 BERENBLUM: The only data available are those of Shubik and co-workers, using beta 

 radiation for initiation and croton oil for promotion in skm carcinogenesis. 

 ROLLER: Prof. Berenblum has certauily tackled a very complicated problem in using 

 C57BL mice to elucidate the two factors mvolved in leukaemogenesis. The explanation 

 which Kaplan and co-workers gave is, that irradiation should not be considered as a 

 factor which 2)roduces the leukaemia, but as a means of creating conditions in the cortical 

 cells of the thymus such that a latent virus might proliferate and turn the cells leukaemic. 

 Kaplan also showed that if he put bone-marrow into the irradiated animals he could 

 prevent the leukaemia developing. Prof. Berenblum said that when he used a single 

 dose of radiation and urthane and followed these with bone-marrow treatment leukaemia 

 was not prevented in these animals. Now I would like to ask him two questions. Does 

 he know the effect of this dose of urthane on the bone-marrow? How soon after urethane 

 was the bone-marrow given to the animals because urethane can destroy the donated 

 bone-marrow and thus frustrate its effects? 



BERENBLUM: The bone-marrow suspension was given 24 hours after the urethane. A shorter 

 interval would have allowed residual free urethane in the body to act on the injected 

 bone-marrow. After 24 hours, most of the urethane is gone. According to the results of 

 Kaplan, 24 hours should be quite sufficient to interfere with radiation leukaemogenesis. 

 roller: What was the histological picture? 



BERENBLUM: According to Rosm and co-workers, urethane depresses the metabolic 

 activity of bone-marrow. 



UPTON: May I compliment Prof. Berenblum on what I consider to be a very exciting and 

 decisive set of experiments. Some of us have toiled for a number of years on this subject 

 and I am really quite thrilled to hear this presentation. I must say, however, that I 

 favour, perhaps on inadequate grounds, the notion that urethane was acting as a promot- 

 ing agent on the host rather than on the completion of an inactive virus. I wonder whether 

 administration of urethane to the filtrate (or cell-free extract) from the donor animal 

 before passage into either a non-urethane treated recipient or, in parallel, a urethane- 

 treated recipient, might help to elucidate this question? 



