MUTAGENS OF POTENTIAL SIGNIFICANCE 231 



remedies that we have in the pharmacopoeia. As far as I know, no 

 thought has been given to what bearing this might have, and to its 

 genetic effects. 



Besides colchicine, there are many other agents that are C-mitotic 

 poisons in plants and cells. Colchicine is merely the most dramatic 

 and the one most widely used experimentally. Chloral hydrate is an- 

 other one which is a spectacular C-mitotic poison. I don't know 

 whether it has been studied in animals, but certainly it has been used 

 very extensively in plant material ; in fact, even before colchicine came 

 into vogue, it was used as a method of producing doubling of chromo- 

 somes. Ether has a C-mitotic effect, as does chloroform, and almost 

 the entire range of what we call the nonspecific narcotics will do 

 very much the same thing in animal cells. Many of these have been 

 studied in nondisjunctional accidents. You get poly astral forms and 

 so forth, by temporary suppression of the spindle. 



I think there may be a legitimate cause for concern that such agents 

 can indeed be responsible for nondisjunctional accidents in the egg, 

 where, of course, they could be most consequential. One has to be con- 

 cerned about using poisons of this kind generally since none of us 

 wants very many of our somatic cells to be unbalanced in their 

 chromosome makeup. At the time of the inception of the zygote, I 

 would assume we would be acutely concerned because we now know 

 what the consequences of chromosome nondisjunction would be. 



Atwood: The maternal age dependence of mongolism shows that 

 practically all the nondisjunctions are in the female, and I think that 

 Dr. Stern has evidence that this is also true for Klinefelter's non- 

 disjunctions. 



Stern: The evidence for meiotic nondisjunction is less binding than 

 we used to think. The age effect could possibly depend on mitotic non- 

 disjunction in an early cleavage division. If so, one would have to 

 assume that the eggs from relatively older ovaries have a tendency 

 to undergo mitotic nondisjunction, perhaps of either maternal or pa- 

 ternal chromosomes. 



Atwood: I mean, it was not an aneuploid sperm that did it? 



Stern: In case of dependence on the age of the mother, chromosomal 

 aberrations in the offspring are, of course, not caused by aneuploid 

 sperm. But we cannot be sure either that it was an aneuploid egg 

 nucleus which was responsible for the aneuploid offspring. There is 

 considerable evidence in man for chromosomally mosaic individuals 

 which must have arisen from mitotic nondisjunction. Even non- 

 mosaic individuals with unusual chromosome constitutions may have 



