136 RADIATION GENETICS 



The frequency of dominant lethals varies with the stage of the cell at the time of 

 irradiation. Mature sperm cells are less sensitive than spermatids but are more 

 sensitive than spermatocytes. 57 ' 58 The cell-stage factor is relatively easy to control, 

 since it now appears that mice do not store mature sperm and the stage at irradiation 

 can be ascertained by control of the time interval between mating and irradiation. 57 

 Bateman's report includes a timetable relating post-exposure week with cellular stage. 



For matings carried out in the first week after exposure, the dose for inducing 

 50 per cent dominant lethals is approximately 700 r for 250 kvp X rays, about 100 r for 

 fast neutrons from a nuclear detonation (average energy ~ 2 Mev), about 100 r for 

 1 Mev cyclotron fast neutrons, and around 300 r for 14 Mev neutrons produced by a 

 Cockcroft-Walton accelerator. 1140 - 1142 In all cases the data for survival of embryos 

 fit a simple exponential equation. Bateman 57 - 59 has made the most recent and 

 thorough theoretical study of the induction of dominant lethals and the relationship 

 between postulated number of chromosomal breaks and time of death of the conceptus. 

 On the basis of his analysis, the dose dependence of dominant lethals proved to be 

 linear for neutron-induced lethals but nonlinear for X-ray damage. This is consistent 

 with the expectation that neutrons will produce more than one hit per ionization track. 



In a series of papers, the Russells have reported on the induction of dominant 

 lethals in female mice. 1123, 1124, 1125 The use of litter size alone is not valid in this sex, 

 since there is a period between 1 and 14 days postexposure when irradiated mice show 

 an excess in ovulation rate. As for studies with males, the pregnant female is sacrificed 

 late in gestation and the number of corpora lutea and living embryos are counted. 

 The ratio of living embryos to corpora lutea is considered an accurate measure of the 

 incidence of dominant lethality. Cellular stage at irradiation is very critical for 

 oocytes and can be ascertained by the interval between exposure and fertilization. A 

 dose of 400 r will induce more than 98 per cent dominant lethality in oocytes in first 

 meiotic metaphase, which occurs 8 to 10 hours prior to fertilization. If the interval 

 between irradiation and fertilization is doubled (16 hours), frequency of dominant 

 lethals drops to less than 20 per cent. For X rays, the dose inducing 50 per cent 

 dominant lethals is about 700 r for primary oocytes, but only about 70 r for the cells in 

 meiotic metaphase. 1120 



Gene mutations. — The greatest interest and concern has been expressed on the 

 following question: what is the radiation-induced mutation rate in a representative 

 laboratory mammal; how does it compare with Drosophila and how can it be applied to 

 man ? For reasons previously noted, the mouse has been the mammal of choice for 

 this critical area of research in radiation genetics. 



The problem can be approached in several ways. The search can be for a total, 

 gametic mutation rate or it can be restricted to specific selected loci. The search can 

 be for dominant visibles, recessive lethals, or recessive visibles. To date, the most 

 successful procedure has been the specific-locus test for the induction of recessive 

 visibles and any associated viability effects, although efforts to make separate estimates 

 of the rates of dominant visible and recessive lethal mutations have also been made. 



