Irradiated Series Research Articles

The ineffectiveness of chronic irradiation with neutrons and gamma rays in inducing mutations in female mice.

Hybrid female mice were exposed to 412 rads 60Co γ rays or 80 rads fast neutrons (+ γ contamination) in 12 weeks and the amount of genetic damage in offspring was compared with controls. Frequencies of specific locus recessive and of dominant visible mutations were very low in the irradiated series, differing little from the control frequencies of nil. There were no significant differences between the sex-ratios of offspring in the three series, thus no evidence for the induction of sex-linked lethal mutations. No estimates can be given of the relative genetic effectiveness of chronic neutron and γ exposures in female mice, but the specific locus mutation frequency after the neutron dose was less than 5 per cent of that obtained in male mice after spermatogonial irradiation with a similar dose over the same 12-week period. It is now clear that both acute and chronic exposures of the immature mouse oocyte to both high and low LET radiations result in minimal genetic damage. It is still not clear whether this applies to the human oocyte also.

Dominant lethal mutations after irradiation of mouse spermato- gonia with 600 R of x-rays.

SummaryMale (101 ♀ × C3H ♂) F1 hybrid mice were irradiated with 600 R of x-rays when 10 to 12 weeks old. One group was exposed to whole-body irradiation, whereas a second group had their gonads irradiated while the trunk was shielded with lead. A third control group remained untreated. At different weeks after regaining their fertility, the irradiated males were mated to either virgin C3H inbred females or to (101 ♀ × C3H ♂) F1 hybrid females. The females were dissected 13·5 to 16·5 days after the appearance of a copulative plug. The numbers of corpora lutea, implants, dead and living embryos were determined. Significant differences concerning both the post- and pre-implantational losses as well as the live embryos were found only between the irradiated series and the controls. More pre-implantational losses occurred after the irradiation of males which were mated immediately after regaining their fertility than after the mating of older ones with a greater interval after irradiation. The fraction of pre-implantation losses was also higher after isolated gonad irradiation than after whole-body exposure and after mating irradiated males to C3H inbred females than to (101 ♀ × C3H ♂) F1 hybrid females. Some further differences of post- and pre-implantational losses did not reach significant levels.

Action des UV sur la recombinaison génétique par irradiation des cellules germinales primordiales chez les drosophiles femelles

An investigation has been made on the UV induced recombination in germinal cells of Drosophila melanogaster females. In these experiments, the Polar-Cap technique developed by Altenburg has been used. About 2 h subsequent to fertilisation at 25°, pole cells appear close to the posterior surface of eggs, where they remain for approx. 70 min. In this position their nuclei can be reached by ultraviolet radiations, provided that eggs are dechorionated before the treatment. The following markers on the second chromosomes were used: black ( b) purple ( pr), engrailed ( en). The dose of UV is 1000 erg/mm 2. The results indicate that (1) the recombination frequencies are greater in the irradiated series than those observed in control series; (2) no anomalies in the segregation pattern of each pair of genes could be detected in the irradiated series; (3) in 7 out of 24 F 1 cultures a positive correlation with reference to increased recombination has been observed between the markers b and pr and between pr and en. These findings suggest a meiotic effect of UV irradiations.

The sensitivity of various germ-cell stages of the male mouse to radiation induced translocations.

Adult male BALB/c mice were given whole body X-irradiation with 300 R. Directly after X-irradiation each male was mated to one virgin female of the same strain and received one fresh female per week during 9 weeks. The male F1 offspring was killed when mature and the testes removed and analysed for the presence of chromosome rearrangements at diakinesis — first metaphase stage of meiosis. Whereas no aberration was recorded among the 171 F1 ♀♀ from the control series, chromosomal abnormalities were observed in 41 F1 ♀♀ from the irradiated series. The incidence of males with aberrations was respectively 5.1% the first week, 10.4% the second week, 21.7% the third week, 2.2% the fourth week and 6.3% the fifth. No aberration was observed in the 129 F1 males sired between the sixth and ninth weeks. It may be concluded that irradiated spermatids yield approximately four times as many cases of aberration in viable F1 ♀♀ as do irradiated mature spermatozoa and about ten times as many as the most mature spermatocytes whereas no aberrations were recovered from irradiation of the spermatogonia. The most common aberrations found in the F1 males of the irradiated series were the reciprocal translocations.

Effects of Chronic Low-Dose Irradiation for Three Successive Generations on the Breeding Behaviour of Mice

SummaryThe effects of radiation on the reproductivity of mice were studied under the influence of chronic low-dose irradiation throughout reproductive period for three successive generations. The dose-rate used was 0·43 r/day, and the accumulated dose was 34·4 r for one generation.Mean litter-size increased with each generation in the irradiated series. Sterility and partial sterility were found in the later generations (P2 and P1 generations), but not in the earlier generations, and the increased incidence in the irradiated series was statistically significant. These may suggest that the radiation effects on reproductivity are, in part at least, cumulative at a very low dose-rate.From the incidence of sterility and partial sterility, the minor chromosome-aberration rate including translocation was calculated at 19·8−6·6 × 10−4/r.

The overall rates of dominant and recessive lethal and visible mutation induced by spermatogonial X-irradiation of mice

1. Hybrid (C3H♀ × 101♂) male mice were given two doses of 600 r. acute x-irradiation eight weeks apart and outcrossed at the end of their sterile period. Their fully fertile sons were outcrossed and daughters of these sons were backcrossed to them, in order to study the rates of induction in spermatogonia of dominant and recessive lethal and visible mutations, as well as dominant semi-sterility.2. F1litter-size decreased by 15·2% at birth and 15·8% at weaning age, as compared with controls. This decrease was very largely due to dominant lethality acting at about the time of embryonic implantation. There was also a highly significant increase in the incidence of heritable semi-sterility, the estimated rate of induction of reciprocal translocations being 3·3% per gamete.3. The dominant lethality was shown to be partly a secondary consequence of induced translocation heterozygosis. The estimated overall rate of dominant lethal induction was 10·6% per gamete, with ‘primary’ dominant lethals induced at a rate of 4·0% per gamete.4. The estimated mutation rate to dominant visible mutations was 4·6 × 10-7/gamete/r., but this was based on only two mutations in the irradiated series.5. In the backcross generation there was again significantly more embryonic death in the irradiated series, mainly at the small mole stage and this was attributed to induced lethal mutation. The survival in the irradiated series was 96·80% of that in the controls and from this the rate of induction of recessive lethals was calculated to be 2·5 × 10-4/gamete/r. There was no evidence of the induction of lethals acting later than 14 days' gestation.6. The estimated rate of induction of recessive visible mutations was 1·8 × 10-5/gamete/r., but the results showed heterogeneity, probably due to personal factors.7. No significant sex-ratio differences were found.8. The results were compared with those of specific locus and other relevant experiments. The rates of induction of recessive lethal mutations and of recessive visibles were both lower than might have been expected. On these results the mouse was only 4–5 times more sensitive thanDrosophilato the mutagenic effects of radiation.

The effect of dose-rate on the yield of translocations and dominant lethals following spermatogonial irradiation of mice

1. F1 (CSH♀ × 101♂) male mice were given 1200 r. 60Co Υ-irradiation over welve weeks and mated twelve weeks after the end of irradiation. The incidences of foetal and neonatal lethality and of semi-sterility in their offspring were compared with those in controls.2. Embryonic survival to 15 days in the irradiated series was 98·2% that of controls, while the incidence of semi-sterility was 0·9% compared with nil in the controls. Neither of these differences is significant.3. Comparison of these results with the significant rates of induction of dominant lethals and translocations in a previous experiment, in which a dose of 1200 r. acute x-irradiation was given to males of the same hybrid stock, show the existence of a dose-rate effect. Its magnitude cannot at present be accurately estimated.4. The reasons for this effect are discussed. It is concluded that the main cause of the lowered translocation yield is that restitution of breaks will be favoured at low dose-rates, with less opportunity for the formation of interchanges. This could partly account for the lowered rate of induction of dominant lethals as well, but a full explanation is not yet possible.

Genetic Variability in Aedes aegypti (Diptera: Culicidae). III. Plasticity in Laboratory Populations1

To assay the amount of hidden genetic variability in laboratory populations of Aedes aegypti (L.), single mosquitoes were selected from cage colonies and inbred by single-pair matings to the F2 generation. The F2 progenies were examined for individuals showing structural variations. These variants were tested for heritability by further inbreeding unless they were phenotypically similar to mutants previously isolated. Consistent use of this criterion permitted an objective comparison of the frequency of mutations in different populations. The samples analyzed contained 52 pairs selected from 4 laboratory strains. Over 22,000 mosquitoes from 424 F2 families were examined for morphological mutations. A total of 137 mutations were estimated to be present in these samples. This gave a frequency of 1.32 mutations per individual. Small differences were observed in the total mutation loads carried by the different populations analyzed; a recently established colony had somewhat fewer mutations than colonies maintained in the laboratory for many years. However, the various populations could be characterized easily by distinct differences in the kinds of mutations each carried. Results of some preliminary tests for mutation frequency in an irradiated series are also given.

Genetic effects of spermatogonial X-irradiation on productivity of F 1 female mice

1. (1) Hybrid male mice were given two doses of 600 R high intensity X-rays eight weeks apart and outcrossed 12 weeks after the second dose. Daughters were also outcrossed and effects on their productivity studied by obtaining data from their first 4 litters at birth and from their fifth at about the 14-day foetal stage. Controls had exactly the same treatment apart from the irradiation. 2. (2) The average number of liveborn per tested female fell by 4.8% from 26.0 in the controls to 24.7 in the irradiated series. The mean litter-size fell significantly by 5.5%. 3. (3) The main factor reducing productivity was inherited semi-sterility in 6.7% of daughters of irradiated males, with none in controls. When combined with data on sons of the same irradiated males this gives an estimated rate of induction of translocations in spermatogonia of 6.4.10 −5/genome/R after two doses of 600 R. This is about one-sixth that reported for spermatozoal irradiation at similar single doses. It is suggested that this differences is mainly due to differential radio-sensitivity of spermatogonial mitotic stages, with only the most condensed stages having a similar sensitivity to that of spermatozoa. 4. (4) The sex-ratio at birth fell significantly from 52.0% in progeny of control daughters to 49.4% in the irradiated series. Other data, however, gave little evidence for the action of recessive sex-linked lethals, or teh presence of XO mice. It was concluded that the sex-ratio decrease was probably due mainly to other unknown causes and that a large-scale experiment with sex-linked markers is necessary if the rate of induction of sex-linked lethals is to be accurately determined. 5. (5) Dominant sub-lethality, sterlity or reduced fertility other than semi-sterility did not seem to play part in the reduction of productivity in daughters of irradiated males.

EFFECTS OF CHRONIC LOW-DOSE IRRADIATION FOR THREE SUCCESSIVE GENERATIONS ON THE BREEDING BEHAVIOUR OF MICE.

SummaryThe effects of radiation on the reproductivity of mice were studied under the influence of chronic low-dose irradiation throughout reproductive period for three successive generations. The dose-rate used was 0·43 r/day, and the accumulated dose was 34·4 r for one generation.Mean litter-size increased with each generation in the irradiated series. Sterility and partial sterility were found in the later generations (P2 and P1 generations), but not in the earlier generations, and the increased incidence in the irradiated series was statistically significant. These may suggest that the radiation effects on reproductivity are, in part at least, cumulative at a very low dose-rate.From the incidence of sterility and partial sterility, the minor chromosome-aberration rate including translocation was calculated at 19·8−6·6 × 10−4/r.

Mutations: Incidence in Drosophila melanogaster Reared on Irradiated Medium

An increase in the rate of mutation has been found in Drosophila melanogaster reared on a basic medium that was irradiated with a sterilizing dose (150,000 rads) of cobalt-60 gamma rays. In Muller-5 tests, sex-linked recessive lethals occurred only in the F 2 progenies of the male test flies obtained from breeding the parent flies on irradiated medium, while visible changes occurred in experimental cultures from both the control and irradiated media. The frequency of sex-linked recessive lethals was 0.35, 0.55, and 0.8 percent in three independent experiments. Visible changes were two to six times more frequent in the irradiated series than in the controls.

Mutations: Incidence in Drosophila melanogaster Reared on Irradiated Medium

An increase in the rate of mutation has been found in Drosophila melanogaster reared on a basic medium that was irradiated with a sterilizing dose (150,000 rads) of cobalt-60 gamma rays. In Muller-5 tests, sex-linked recessive lethals occurred only in the F(2) progenies of the male test flies obtained from breeding the parent flies on irradiated medium, while visible changes occurred in experimental cultures from both the control and irradiated media. The frequency of sex-linked recessive lethals was 0.35, 0.55, and 0.8 percent in three independent experiments. Visible changes were two to six times more frequent in the irradiated series than in the controls.

Cytological and morphological changes induced in tomato as a result of thermal neutron irradiation

Seeds of two species of tomato, Lycopersicon esculentum, Mill. and L. pimpinellifolium Dunal were irradiated with thermal neutrons. One lot of seeds of each species was irradiated for 20 hr at a flux of 7·63×10 8 thermal neutrons/cm 2/sec and a second lot was irradiated for 30 hr at a flux of 7·63×10 8 thermal neutrons/cm 2/sec. Microscopic examination of normal apices shows that the apex consists of a two-layered tunica which encloses a corpus. Examination of the apices from the irradiated series shows one or more modifications to occur: (1) change of the plane of cell division occurring in the tunica region—i.e., periclinal divisions occur in the most centrally-located cells of the first tunica layer; (2) periclinal division of the cells of the second tunica, layer in conjunction with such divisions occurring in the T-1 layer; (3) complete disorganization of the second tunica layer so that the corpus continues unbroken from the first tunica layer; (4) lysis of the most centrally-located cells of the T-2 layer. Modifications of the corpus region seen to occur are: (1) an increasingly irregular organization of the planes of cell division; (2) earlier maturation of cells of the corpus as the result of either an acropetal advance of the inception of the vascular tissues or the inception of the pith rib meristem in closer proximity to the T-1 layer; this modification, in turn, appears to exert an influence on the general outline of the generative region. The possible significance of the above-described modifications is discussed. Radiation damage common to both growth zones is exemplified by collapse of the cells followed by a general tissue breakdown of that area of the apex.

Dose, Time and Volume Parameters in Irradiation Therapy of Kaposi's Sarcoma

In a recent review on the treatment of Kaposi's sarcoma (Cohen, Palmer and Nickson, 1962), it appeared that there was relatively little information published on its radiosensitivity, and that reported methods of management varied widely and were often contradictory. It has, however, become possible, since the disease is of extraordinary frequency in Africa, to present the following analysis of a comparatively large irradiated series from which appropriate data can be extracted. The pathological and clinical features of this African series are described in detail by a number of investigators (U.I.C.C. Symposium on Kaposi's Sarcoma, 1962, in press); the present report deals with the radiosensitivity of the individual lesions and the tolerance limits of the associated normal tissues. Between 1949 and 1960, 58 cases of typical Kaposi's sarcoma were referred to the Radiation Therapy Department of the Johannesburg Hospital for therapy. Of these, 16 were lost to follow-up yielding no information on the length of...

Effects of Total-Body X-Irradiation in Utero on Early Postnatal Changes in Neuron Volumetric Relationships and Packing Density in Cerebral Cortex

After exposure to a cumulative dose of 300 r of totalbody x irradiation on gestation days 10 to 14 inclusive, only small differences in neuron nuclear volume, cytoplasmic volume, soma volume, and packing density between irradiated and control series were observed between the first and twentieth posthatal days. However, marked differences were observed in cortical thickness in five different areas at all developmental stages between the control and irradiated groups. The growth curves for cortical thickness for irradiated and control groups tended to be parallel in each specific area. Brain weight was found to be significantly less in the irradiated than in the control animals, as was cortical thickness. From the available data it appears that, although the total number of cells in the cortex is greatly reduced by in utero irradiation at the dose and rate levels employed, the surviving cells tend strongly to follow normal growth patterns and establish their normal spatial integrity. (auth)