MUTAGENS OF POTENTIAL SIGNIFICANCE 223 



Auerbach: We are doing this now with mice. Dr. Cattanach is going 

 to give our mice coffee to drink. We are working on too small a 

 scale to do the kind of specific loci tests that the Russells are doing. 

 We can only test for dominant lethals and translocations. The difficulty 

 there is that if caffeine should act only on spermatogonia, Cattanach 

 may not be able to detect its efTect, because most dominant lethals 

 are screened out in meiosis, and translocations occur infrequently in 

 postmeiotic cells. On the other hand, the Drosophila experiments sug- 

 gest that caffeine produces mutations in postmeiotic stages. 



Novick: I would like to raise a genetic question among the human 

 geneticists. Do we not already have some suggestion of what the upper 

 limit is in the human, in some sort of terms? We can then set up an 

 irradiation equivalent that man is exposed to, that is, coffee-drinking 

 man. How big can the caffeine effect be to go unnoticed? 



Lederberg: It depends on the age dependence. 



Novick: How much is due to radiation? 



Lederberg: Who knows what the radiation efficiency is? 



Neel: The NAS committee suggested that the doubling dose in man 

 was almost certainly between 10 and 150 r, with the true value very 

 probably to be placed in the 30 to 80 r range. 



Novick: So this, then, is a likely caffeine dose. 



Glass: There is some more recent evidence from mouse work (50) 

 that tends to support 30. 



Lederberg: These are subject to exactly the same sort of criticisms 

 that have been brought up here; I mean, they are all the most 

 reasonable extrapolations you can make. We don't know the mutation 

 rate in man. We don't know the efficiency of radiation. 



Neel: What is your estimate for the doubling dose for specific 

 loci in mice? 



Russell: I'm surprised at talk of the doubling dose. It depends upon 

 the locus. It depends upon whether you are talking about sperma- 

 togonia, spermatozoa, or oocytes. It differs for chronic and acute ir- 

 radiation, and so on. There is no one doubling dose. Even an attempt 

 to make a quantitative average of some of these factors is not of much 

 value, because there are qualitative differences involved, too. There 

 are qualitative differences between the mutations induced in sperma- 

 tozoa, spermatogonia, and oocytes, and between at least some of these 

 and those occurring spontaneously. 



Neel: Very well, let us consider male mice receiving chronic radia- 

 tion to their spermatogonia, which would correspond to chronic 

 coffee-drinking. The next question is at what rate is the radiation 



