742 RADIATION GENETICS 



of the mouse do not challenge the basic Drosophila data. The dose-rate effect is 

 definitely limited to spermatogonia and oocytes. 1140, 1142 It should also be noted that 

 a significant dose-rate effect has now been demonstrated for Drosophila oogonia exposed 

 to Co 60 gamma radiation. 972 The flies were exposed to a total dose of 4,000 r over 

 either a period of two weeks or in 31 seconds. The percentage of sex-linked lethals 

 was 1.3 + 0.5 and 3.4 + 0.7 for the continuous and single-dose exposures, respectively. 

 The difference is significant. 



Studies on microorganisms indicate that some portion of the induced genetic 

 damage falls into a category now labelled as premutational damage. A recovery 

 process, requiring active protein synthesis, acts to prevent the fixation of part of the 

 premutational damage, thus reducing the mutational yield. 514, 708 The reduced 

 mutation rate in mouse gonia and oocytes following low intensity irradiation is inter- 

 preted to be the result of a process of metabolic recovery, which may itself be quite 

 radiosensitive and therefore fail under high-intensity irradiation. The study of 

 mutation at the molecular level has therefore become of increased importance, and 

 new insight into the mechanisms of radiation protection may also result. 



Important unanswered questions now concern the effects of fractionated ex- 

 posures in all their complexities of interminable variables. Is there a limiting low dose 

 rate, above which the mutation rate jumps to the higher level? Will there be all 

 gradations between the high and the low ? What will be the effect of intermittent 

 exposure at high intensities but to very small doses? If the answer to this previous 

 question is that the low mutation rate prevails, will it do so only under specific condi- 

 tions of dose rate, dose per fraction, and fractionation interval ? These questions are 

 important for both industrial and medical situations where there is often no regular 

 pattern of exposure. 



In addition, the dose-rate effect requires careful evaluation with exposure to the 

 densely ionizing radiations, such as alpha particles and fast neutrons. Because of their 

 greater efficiency in inducing genetic and general cellular damage, is it possible that 

 exposure to neutrons, for example, may produce more concurrent injury to the pre- 

 sumed recovery mechanism and thus a lesser reduction in mutation rate with declining 

 dose rate ? The neutron may be of particular value in these genetic studies because 

 of its known peculiar behavior with regard to somatic lethal effects. Let me refer to 

 two studies as an example. Sproul, 1262 using the traditional paired-dose technique to 

 estimate recovery from acute radiation injury, found that the rate of recovery is essen- 

 tially the same following initial exposure of the whole body to a single dose at high 

 intensity of either Co 60 gamma rays or 14 Mev neutrons. On the other hand, Upton 

 et a/. 1336 have indicated that the RBE for shortening of life induced by neutrons pro- 

 duced by a Po-Be source (~4 Mev) progressively increases as the dose rate declines. 

 The data suggest that the long-term, lethal effects of neutrons are considerably less 

 dependent on dose rates than are those following Co 60 gamma irradiation. It is 

 entirely conceivable that genie mutational damage induced by fast neutrons may also 

 be less dependent on dose rates. 



