Discussion 137 



We have also investigated a number of amines, which are known to 

 protect mice excellently, like histamine, epinephrin and phenylethyl- 

 amine, and it was found that these compounds do not show any protective 

 activity with isolated cells. We think that the protection of mice by 

 these amines may be the result of their activity on some organ system 

 e.g. the cardiovascular or the respiratory system, and it seems possible 

 that part of the protective activity of cysteamine in vivo is due to a 

 similar mechanism. Have you any information on the pharmacological 

 effects of cysteamine ? 



Hollaender : Yes, we have. This is work which has been done at the 

 University of Rochester, it is not completed and that is why I didn't 

 mention it. AET as well as cysteamine have a depressive effect on the 

 respiratory centres in the cat. AET is more toxic to the dog than to the 

 mouse. Preliminary tests in monkeys have shown that AET is less toxic 

 to the monkey than to the dog. The effect is different in different species 

 of animals. This, of course, requires very careful investigation before 

 we w ould say it is of practical significance. 



Spiegelman: I should like to cite here an interesting experiment per- 

 formed by Norman (1953, J. Bad., 65, 151) which is relevant to some of 

 the points raised by Dr. HoUaender's paper. Norman grew cells in a 

 glucose minimal medium, irradiated them with u.v., and then plated 

 them on minimal media containing glucose in some cases and other 

 carbon sources in others. On plotting the log of the survivors measured 

 on these different plates, he found a much greater apparent kill if the 

 cells were plated on a carbon source different from the one on which they 

 had grown up. Thus, glucose-grown cells show a much greater kill when 

 plated on lactose as compared with glucose. That this apparent increase 

 in sensitivity is associated with a demand for the formation of new 

 enzyme is shown by experiments in which he grew the cells up in lactose 

 and plated them on lactose minimal medium. In such cases the apparent 

 kill was the same as when plated on glucose. 



Latarjet: This is u.v. work — it destroys the adaptation. 



Spiegelman: Yes, but the interesting thing to emerge from this 

 experiment is the following. First, it must be noted that all you are 

 asking the glucose cell to do, on being plated on lactose, is to make one 

 more enzyme, and this apparently makes an enormous difference. In 

 addition, when the killing curves obtained from the glucose and the 

 lactose plates are extrapolated back, they both give the same average 

 hit number required for kill and the value is about 1-2. This would 

 suggest that a nuclear phenomenon is involved. It would seem to me 

 that a more extensive investigation of this phenomenon is extremely 

 desirable. It is an experimental situation in which the comparative 

 conditions on the glucose and lactose minimal media are under experi- 

 mental control and where the enzymatic consequences are also pretty 

 well defined. 



Haddow: Dr. Hollaender, have you done any tests on protection 

 against carcinogenesis with AET ? 



Hollaender: These are in progress now. Many of these malignancies 

 appear fairly late, it takes a period of about two years to be sure that 



