W. L. Russell

Radiation dose rate and mutation frequency.

New data have clearly confirmed the earlier finding that specific locus mutation rates obtained with chronic gamma irradiation of spermatogonia are lower than those obtained with acute x-rays. Since this result is in contrast to classical findings for Drosophila spermatozoa, and apparently contradicts one of the basic tenets of radiation genetics, it was important to determine what factors were responsible for it. Experiments undertaken for this purpose reveal the following: (i) the lower mutation frequency is due mainly to difference in dose rate of radiation, rather than quality; (ii) a dose-rate effect is not obtained in experiments with mouse spermatozoa, confirming classical findings for spermatozoa, and indicating that the explanation for intensity dependence in spermatogonia resides in some characteristic of gametogenic stage; and (iii) a dose-rate effect is found not only in spermatogonia but also in oocytes, where cell selection is improbable, indicating that the radiation intensity effect is on the mutation process itself. A threshold response for all mutations in spermatogonia and oocytes is not a necessary consequence of the findings. Plausible hypotheses consistent with the present results can lead to other predictions. From a practical point of view, the results indicate that the genetic hazards, at least under some radiation conditions, may not be as great as those estimated from the mutation rates obtained with acute irradiation. However, it should not be forgotten that even the lower mutation rates obtained with the present intensity levels are still appreciable (16).

Effects of ENU dosage on mouse strains.

Abstract. The germline supermutagen, N-ethyl-N-nitrosourea (ENU), has a variety of effects on mice. ENU is a toxin and carcinogen as well as a mutagen, and strains differ in their susceptibility to its effects. Therefore, it is necessary to determine an appropriate mutagenic, non-toxic dose of ENU for strains that are to be used in experiments. In order to provide some guidance, we have compiled data from a number of laboratories that have exposed male mice from inbred and non-inbred strains or their F1 hybrids to ENU. The results show that most F1 hybrid animals tolerate ENU well, but that inbred strains of mice vary in their longevity and in their ability to recover fertility after treatment with ENU.

RADIATION HAZARDS TO THE EMBRYO AND FETUS

The radiosensitivity of the embryo and fetus is a matter of great practical importance to radiologists, gynecologists, and obstetricians. It is unfortunate, therefore, that the literature on this subject is diffuse and contains numerous apparently contradictory reports and opinions. Cases of grave radiation injury to the embryo or fetus have been summarized and discussed by Goldstein and Murphy in 1929, Gauss (quoting a thesis by Kraemer) in 1930, Flaskamp in 1930, and Miller, Corscaden and Harrar in 1936. Since the time of these reviews, more cases have been described by Murphy, Shirlock and Doll (1942), Jones and Neill (1944), and others. On the other hand, there are scattered reports of normal births following heavy doses of radiation: Robinson (1927) has collected 23 such cases from the earlier literature, Lacomme (1931) reports 2 and Hobbs (1950) 1. Results from recent extensive animal experiments fall into an easily comprehensible over-all picture which dispels some of the apparent contradictions in...

Strain and sex variations in the sensitivity of mice to dominant-lethal induction with ethyl methanesulfonate.

Abstract Male and female mice from two hybrid strains and a random-bred one were subjected to dominant-lethal induction with ethyl methanesulfonate. In female mice, 1 strain revealed a strong mutagenic action of ethyl methanesulfonate while the other 2 strains did not. In male mice, all 3 strains exhibited high sensitivity to the mutagenic action of ethyl methanesulfonate with only minor strain differences. The results thus revealed the existence of large sex differences in 2 of the 3 strains and large strain differences in the response of females.

The Relative Effectiveness of Neutrons from a Nuclear Detonation and from a Cyclotron in Inducing Dominant Lethals in the Mouse

Dominant lethality in the offspring of male mice exposed in lead hemispheres to neutron radiation from a nuclear detonation was determined for ten different doses by mating the males to unexposed females, dissecting the females at a late stage in pregnancy and recording the number of living and dead embryos, resorption sites and corpora lutea. Data from early matings (2 to 6 days after irradiation) and late matings (19 to 31 days after irradiation) were tabulated separately. Comparison of the results with those from a similar experiment with fast neutrons from a cyclotron shows: 1. For comparable levels of total effect, the two sets of results do not differ significantly in the distribution of deaths according to age of embryos. 2. The increase in dominant lethality observed when the offspring of late matings are compared with those of early matings is similar in the two experiments. 3. The biological effectiveness of detonation neutrons relative to cyclotron neutrons lies between 0.80 and 1.18, the minimum and maximum estimates obtained when allowance is made for uncertainty in the physical measurements of the gamma radiation contamination in the detonation experiment. (Taking the biological effectiveness of cyclotron neutrons relative to X-rays as 8.0, the corresponding minimum and maximum estimates of the biological effectiveness of detonation neutrons relative to X-rays are 6.4 and 9.4, respectively.) It may be concluded that, although there is a marked difference in intensity, and presumably some difference in energy spectrum, between the detonation and cyclotron neutrons, the present data show no significant difference in the effectiveness of these neutrons in inducing dominant lethality in mice.

Influence of dose rate on radiation effect on fertility of female mice

Summary 1) In an attempt to contribute to an understanding of unusual radiation sensitivity exhibited by the mammalian oocyte, a non-dividing cell, fertility experiments were carried out to determine the effect of dose rate (fractionation, different intensities of continuous radiation). 2) Fractionation markedly reduced damage to fertility; and division of dose into 10-r fractions was more effective in this respect than division into 25-r fractions. Continuously exposed females were even less affected in breeding performance than females which had received fractionated irradiation, and the lower the dose rate the smaller was the deleterious effect on fertility. In all groups, production, in terms of number of females casting litters, remained at maximum level until beginning of a sudden steep decline that ended in sterility. It is for this reason that some experiments of other investigators, who have measured performance only in terms of the first postirradiation litter, have failed to show similar dose-rate effects. 3) The results indicate that some repair of radiation damage to oocytes can occur, and that repair is greater at lower dose rates.

Effect of X-ray and ethylnitrosourea exposures separated by 24 h on specific-locus mutation frequency in mouse stem-cell spermatogonia

Specific-locus mutation frequencies in mouse stem-cell spermatogonia were determined in 3 experiments in which mature male mice were exposed to 100,m 300, or 500 R of X-rays followed, 24 h later, by intraperitoneal injection of 100 mg/kg of ethylnitrosourea (ENU). The purpose was to find out if the mutation frequencies would be augmented over those expected on the basis of additivity of the effects of the separate treatments. Such augmentation had been observed in earlier work in which exposure to 100 or 500 R of X-rays was followed 24 h later by a second exposure of 500 R. No augmentation was observed for X-rays followed by ENU. The mutation frequencies in all 3 experiments actually fell below those expected on the basis of additivity, although the reductions were not statistically significant.

Relation of Mouse Specific-Locus Tests to Other Mutagenicity Tests and to Risk Estimation

Several years ago, when concern over the possible human genetic hazards from chemicals was first becoming widespread in the scientific community, markedly different views of possible risk were being expressed. At one extreme, there were predictions that, because detoxification systems in mammals are so effective, noxious chemicals would be prevented from reaching the gonads, or the genes in the germ cells, and would therefore present much less risk to the human population than penetrating ionizing radiation. At the other extreme, there were calculations, based on the mutagenic effects of caffeine in lower organisms, that coffee consumption alone could be causing a vastly greater genetic hazard than that from the total exposure to ionizing radiation.