MAMMALIAN RADIATION GENETICS 133 



were detected, a radiation origin could not be substantiated. Snell 1250 and Hertwig 551 

 did report positive evidence for the induction of gene mutations in mice by X irradiation 

 several years after Muller had reported this for Drosophila. All of the early literature 

 has been completely and excellently reviewed by Griineberg 507 and Russell, 1128 and 

 anyone considering entering the field of mammalian radiation genetics would be well 

 advised to review the pioneering efforts of G. D. Snell, P. Hertwig, H. Brennecke, and 

 their co-workers. 



INDUCED STERILITY 



Prior to any consideration of genetic analysis, the problem of radiation-induced 

 sterility must be faced. Interest in this field traces back to the early part of the cen- 

 tury 743 and considerable activity continues to the present. It is, of course, a problem 

 of practical concern to the radiation geneticist, since certain experimental conditions 

 may be precluded by the induction of either temporary or permanent sterility. A 

 certain amount of trial-and-error methodology is still required for many species, since 

 only the male mouse has been studied in fairly complete detail. 328, 952 - 953, 955, 957 The 

 work of Oakberg can be considered a model for those who wish to study the sterilizing 

 effects of ionizing radiation. He has pointed out the need for careful timing of post- 

 irradiation intervals for sampling, exact identification of cellular type and maturation 

 stage, and the need for correction for architectural distortion due to shrinkage of 

 tubules. Spermatogonial cells of the mouse are extremely sensitive to radiation and 

 have an ld 50 dose of 20 to 24 roentgens. An increase in cellular death is even detected 

 at single doses as low as 5 rad of gamma rays or 2 rad of fast neutrons. 1142 



Johnson and Cronkite 664 used Oakberg's techniques in a recent study to evaluate 

 the effect of tritiated thymidine on spermatogonial cells. Since exact dose rate and 

 total dose from the tritium are not known, a comparison with data from external 

 radiation permits use of the curve for cell-killing as a bioassay. A dose of 1 [xr/gram 

 of body weight, for example, after 60 hours of exposure produced an effect equivalent 

 to something less than 5 r of external, Co 60 , gamma radiation. 



The reproductive performance of irradiated males will vary from species to species 

 with respect to dose sensitivity, duration of reduced fertility or complete sterility, and 

 time of recovery to near normal fertility. As a general rule, there are three distinct 

 periods: the pre-sterile period that immediately follows exposure, the sterile period, 

 and the post-sterile period. During the pre-sterile period, fecundity gradually declines 

 as post-meiotic germ cells are cleared through. This period is used for the study of 

 dominant-lethal induction rates, translocation rates, and mutation rates in spermato- 

 cytes, spermatids, and spermatozoa. The post-sterile-period matings are used to 

 study mutations induced in spermatogonial cells. Thus, the stage of the cell at the 

 time of exposure can be quite accurately defined for genetic analysis. 



The sterilizing effects of radiation of the female have not been as thoroughly 

 investigated as in the male, but there is a tremendous species factor in radiosensitivity. 



V 



