MUTAGENS OF POTENTIAL SIGNIFICANCE 183 



Russell: I think some kind of answer is available, but I don't have it 

 "with me. 



Goldstein: Can we make any kind of guess? The guess that Dr. At- 

 wood made the other day was 100 days. 



Atwoocl: That's for bone marrow. It's probably not too different, 

 though. 



Russell: In the female mouse, all mitotic divisions are completed 

 before birth, and this is almost certainly true in the human. At 72 

 hours after birth, in the mouse, the oocytes go into what is called the 

 dictyate stage, and they stay in this one cytological state until a few 

 hours before ovulation. In short, there is no cell division of any kind 

 in the oocytes, or chromosomal divisions, throughout the large part of 

 the life of a mouse. Yet we can induce mutations in this period. 



Goldstein: But not necessarily by such substances as would act dur- 

 ing replication cycles. You can induce mutations with radiation. 



Russell: That is a very important point. 



Goldstein: Yes, it is because, once we accept this point, it means 

 that the risk of exposure to mutagens of that type can be ignored for 

 the female, except during the fetal period of growth. 



Lederberg: What you are saying. Dr. Russell, is that for the female 

 mouse, the second and third terms don't apply because there is no 

 stem line after birth, and the fourth term doesn't apply, either, so 

 there would just be a constant term for this type of mutation. As Dr. 

 Atwood also mentioned, there would be no age dependence. What about 

 the male? 



Atwood: The fourth term has a value of two generations in the 

 female. 



Lederberg: That's right. But this is in conflict. 



Russell: I think you're trying to restrict things to the molecular 

 level in a way which may be an oversimplification when the kind of 

 things Dr. Auerbach was talking about yesterday can be paramount. 



Lederberg: I think we're asking histometric questions. Is it possible 

 to say how many divisions are involved in the production of the germ 

 tissue up to puberty as a constant term, and then, what is the turnover 

 rate of the germ line subsequent to puberty? 



Russell: As I said, I think rough answers can be obtained. 



Goldstein: Let's suppose the value 30 is correct for mi, the cell gen- 

 erations leading to the establishment of the germ line. We can certainly 

 agree that m4 will be a very small number. Then supposing that the 

 mean generation time in the germ line were 100 days, as Dr. Atwood 

 suggested for bone marrow, it is clear that the age effect becomes im- 

 portant only at a certain point, namely, when mo + ms reaches the 



