138 Discussion 



they don't have any. Dr. Upton in our laboratory is now maintaining a 

 large colony of mice which have survived this irradiation. We are 

 watching for leukaemias and also for other malignancies. But it may 

 take another year to be certain. 



Laser: I have tried it with yeast and have obtained quite conclusive 

 results but with opposite effect. Yeast is grown in a synthetic medium 

 containing all the growth requirements, with glucose and ammonium 

 sulphate as the only sources of carbon and nitrogen. This yeast, when 

 grown in the same medium after irradiation, shows a strong irradiation 

 effect. However, if the irradiated yeast is transferred into a medium in 

 which the ammonium salt is replaced by another nitrogenous substrate 

 to which the cells may have to adapt, the radiation effect is diminished 

 and still more so if the glucose is also replaced by a different carbon 

 source, say galactose. 



Spiegelman: I don't understand. What do you plate on? 



Laser: I don't plate, but grow the yeast in a liquid medium and 

 measure growth rates either by optical or manometric methods. I find, 

 as already stated, that by changing after irradiation either the carbon 

 or the nitrogenous source or both — that is, by initiating adaptation — 

 the irradiation effect has become less apparent. 



Spiegelman: Your killing is less? 



Laser: Yes. 



Popjak: I would like to raise some questions about the mechanism 

 of action of these chemical protectors. It has been said, in the case of 

 cysteamine for example, that it might be that it protects the "business- 

 end" of coenzyme A. Then it has been suggested that it acts like cysteine 

 and other readily oxidizable substances by virtue of taking up preferen- 

 tially oxidizing radicals, or by reducing tissue oxygen tension, this being 

 merely some kind of nitrogen effect. It seems to me that there might be 

 some other explanations for the protective action of cysteamine. 

 It appears that the free amine group is very important in protection, 

 because substitution on the nitrogen with alkyl groups eliminates the 

 protective action. Eldjarn and Pihl have reported that cysteamine 

 does combine very rapidly with the SH groups of proteins. If that is so, 

 then one might expect that cysteamine and analogous substances might 

 cause a reversible inhibition of enzymes. I have done some experiments 

 on this point and these support my assumption. It may be that cyste- 

 amine protects enzymes during the period of irradiation by combining 

 with some vital groups on the enzyme, rather than by catching oxidizing 

 radicals. 



Hollaender : It just keeps the radicals from getting to a group by 

 protecting them? 

 Popjak: Yes. 



Gale: There seem to be a number of analogies between the material 

 that we have just been given and the action of penicillin. I noticed 

 particularly one of the slides that Dr. Hollaender showed, where there 

 appeared to be an effect of radiation resulting in decreased synthesis 

 of RNA, and increased accumulation of the "acid-soluble RNA". I 

 wonder if you can tell us anything about the nature of substances which 



