MANNER OF PRODUCTION OF MUTATIONS 577 



Drosophila, in order to be valid, requires that the lots of parent flies used 

 in the comparisons be genetically quite alike, raised under the same condi- 

 tions except with respect to the agent studied; that they be of the same 

 age and have the germ cells used in the same state of maturity when 

 irradiated; and that the later generations, in which the mutations are 

 scored, be alike in regard to the environmental as well as genetic condi- 

 tions obtaining in order that similar conditions of selection may exist. 

 More recently, benzopyrene has been reported to affect the X-ray muta- 

 tion rate in Drosophila (Fabian and Matoltsy, 1946). It appeared to 

 lower the mutation rate, although in Vicia it has since been reported 

 (Cottet and Minder, 1947) to increase the frequency of chromosome 

 changes produced by X rays. 



In the absence of irradiation, many chemicals have been shown 

 cytologically to increase the frequency of chromosome breakage and 

 aberrations, and a considerable number (some of them the same chemi- 

 cals) have also been shown to influence the frecjuency of visible and/or 

 lethal mutations, as noted in reviews by Auerbach (1952) and by Jensen 

 et al. (1952). It would be surprising if some of these chemicals did not 

 act synergistically with radiation, but few such tests except those already 

 mentioned involving nitrogen mustard, oxygen, and cyanide, respectively, 

 have yet been reported. It is also to be expected that some chemicals 

 which are ineffective by themselves would be mutagenic with radiation. 

 Some instances of this kind have been noted in this section, but a really 

 systematic study along these lines has as yet hardly begun. In fact, 

 many of the very substances which have been found to be effective, 

 without radiation, in producing genetic changes in one of the two general 

 categories (point mutations and demonstrable results of chromosome 

 breakage) have not yet been tested on the same material in regard to their 

 mutagenicity for the other category. It is still too early to know whether 

 marked differences in these respects exist, except for those instances of a 

 differential effect with radiation which have already been cited. More- 

 over, even in these instances, it is not clear whether the observed differ- 

 ence is real in the sense that gene mutations and breaks are differently 

 affected or whether the apparent difference has been caused by an 

 influence on the joining of ends. 



Except where the cell stage treated can be exactly controlled (as when 

 mature spermatozoa are used), effects on the radiation-induced mutation 

 rate can be produced indirectly by chemicals, through an influence of 

 them on the cell stage. For example, since aberrations (and probably 

 also gene mutations) are more readily induced in mitotic and near- 

 mitotic stages, chemical and other agents which increase the frequency of 

 mitosis, or prolong it, will, as pointed out by KoUer (1946), cause an 

 increase in the frec^uency of genetic changes produced by radiation. 

 Notable instances of such substances are furnished by colchicine, acenaph- 



