Frequency of spontaneous chromosome aberrations in mice: effects of age

In this paper, we present data on chromosome aberration frequencies in mice which served as unexposed controls in a variety of radiation and chemical toxicology experiments conducted in our laboratory in recent years. All chromosome aberration data were obtained by chromosome painting. In peripheral blood lymphocytes from 102 animals, the frequencies of translocations and insertions increased significantly with age. No increase with age was seen for dicentrics or acentric fragments. When the data were analyzed by strain, the age-related increase in translocation frequencies was observed only in the 71 homozygous C57BL/6 mice and not in any of the three heterozygous strains. Very few aberrations of any type were observed in 62 bone marrow samples, and no effect of age was seen for any aberration type in this tissue. These results are similar to those observed in unexposed humans, and suggest that the increase in translocations is not the result of accumulated damage from chronic 'background' environmental exposures but instead may be due to biological processes associated with aging.     

Elimination of spontaneous and chemically induced chromosome aberrations in mice during early embryogenesis

Summary NMRI mice () were treated with 0.25 mg/kg body weight Trenimon (2,3,5-triethyleneiminobenzoquinone-1,4) in the preovulatory phase just before ovulation. Then they were mated with untreated males.The female mice were dissected 45 h after application of this mutagen. The preimplantation embryos, being in a 2-cell stage, were flushed out of the oviduct and cultured in vitro for 60 h. Of the cultured embryos 87.7% reached the blastocysts stage in the control series, whereas only 49.7% did so in the experiments.Some of the females were dissected on the 14th day post conception (p.c.) and the number of dead and living implants was determined.Furthermore, the 9.5- and 13.5-day-old embryos were cytologically investigated, to determine the frequency of chromosomal aberrations.Of the unfertilized oocytes 76.2% deriving from mice treated with 0.25 mg/kg Trenimon, were aberrant in the stage of metaphase II (Röhrborn and Hansmann, 1971).Comparing Röhrborn's and Hansmann's results (1971) to our own findings a continous elimination of chromosome aberration is clearly to be seen during early embryogenesis. The biological selection takes place in the pre- as well as in the early and late postimplantative phase.     

Two types of double-strand breaks in electron and photon tracks and their relation to exchange-type chromosome aberrations

Yields of DNA double-strand breaks (dsb), i. e. the average number of dsb, N–, per relative molar mass, M _r , and dose, D, produced by electrons and photons in the energy range 50 eV – 1 MeV were calculated. The experimental data of dsb induction by ultrasoft x-rays and by photons agree well with the calculated yields of dsb as a function of photon energy. The dsb are classified into simple and complex ones. Energy transfers of less than about 200 eV producing at least two ionizations generate mainly simple dsb, while low-energy electrons with an initial energy between 200 and 500 eV induce preferentially complex dsb. Assuming that dsb is the main DNA lesion leading to exchange-type chromosome aberrations (etca), three different mechanisms have to be considered: 1) complex dsb on its own; 2) interaction between two dsb induced by the same primary particle; and 3) interaction between two dsb induced by different primary particles. Mechanisms 1) and 2) produce a linear term, whereas mechanism 3) leads to a quadratic term for the yield of etca. The sum of contributions 1) and 2) to the yield of dicentrics describes fairly well the non-trivial structure of the experimental data. The results suggest that interaction between complex dsb does not contribute significantly to the formation of dicentrics via mechanism 3). Received: 30 July 1995 / Accepted in revised form: 28 March 1996     

Tritiated uridine induced chromosome aberrations in relation to heterochromatin and nucleolar organisation in Microtus agrestis L.

Microtus agrestis is characterised by long sex chromosomes, most of which are constitutively heterochromatic, and thus supposedly, genetically inactive. A method to assess the template activity of the chromosomes is to study the distribution of chromatid aberrations produced by H³UdR, among and within the chromosomes. In such a study, in female Microtus agrestis cells in culture, it was found that, a large number of localised chromatid aberrations was induced in the constitutively heterochromatic regions of both X chromosomes. The frequency distribution and types of aberrations were found to be cell cycle dependent. With differential staining it has been possible to demonstrate that the constitutive heterochromatin of the sex chromosomes are involved in the nucleolar organisation in this species, thus containing the ribosomal RNA cistrons.     

The localisation of radiation induced chromosome aberrations in relation to the distribution of heterochromatin in Secale cereale

The distribution of two break chromosome exchanges (dicentrics and centric rings) following gamma or neutron irradiation of resting seeds of rye, Secale cereale, has been investigated. The localisation of heterochromatin in the terminal ends of the chromosomes of rye facilitates distinguishing aberrations involving heterochromatin from others. Dicentrics found in or near heterochromatic regions were about 5 times more frequent after gamma irradiation and about 2.5 times more after neutron irradiation, than expected on a random distribution. The implications of these findings in relation to aberration formation are discussed.     

Cell survival and radiation induced chromosome aberrations

Human peripheral lymphocytes were irradiated in whole blood with 0.5-4.0 Gy of 220 kVp X-rays and the frequency of chromosome aberrations was determined in 1st or 2nd division metaphases discriminated by fluorescence plus giemsa staining. Using the empirical distributions of aberrations among cells, cell survival and transmission of aberrations were investigated. Considering both daughter cells, we found that 20% of fragments and 55% of dicentrics or ring chromosomes are lost during the 1st cell division; i.e. cell survival rate from 1st to 2nd generation is mainly influenced by anaphase bridging of these two-hit aberrations. Cell survival to 2nd mitosis was calculated considering this situation and compared with the survival derived from the fraction of M 1 cells without unstable aberrations. The resulting shouldered survival curves showed significantly different slopes, indicating that cell reproductive death is overestimated in the latter approach.     

Cell survival and radiation induced chromosome aberrations

Summary Existing mathematical formulations to predict the frequency of radiation induced chromosome aberrations in 2nd post-irradiation division are based on the Poisson distribution [3, 4]. Meanwhile several studies have shown that intercellular distributions exist, deviating from Poisson. In the present study a modified model was developed which permits the application of empirical distributions. Transmission and survival parameters of aberrations can be iteratively computed. A general formula was derived for the calculation of cell survival from 1st to 2nd division.     

Radiation induced chromosome aberrations and the poisson distribution

Summary Data on the distribution of dicentrics and acentrics observed when human lymphocytes are cultured for 48 h after irradiation by X-rays,-rays, and neutrons are presented. Analysis shows that for dicentrics, the observed distribution for X-rays,-rays, and fission neutrons may be described by Poisson statistics but for higher energy neutrons overdispersion is observed. The phenomenon of overdispersion is also observed for acentrics irrespective of the radiation used. The possibility that overdispersion results from the variations of dose in sensitive sites leads to the conclusion that for dicentrics the site size is considerably larger than the 1–2 µm diameter derived by applying the dual action theory to the dose effect relationships. This larger site may well be the cell nucleus.     

Significance of structural chromosome aberrations in human sperm: analysis of induced aberrations

Summary A significant increase in the incidence of structural chromosome anomalies has been observed in the sperm of patients treated with radio and/or chemotherapy for different types of cancer when analyzed by the interspecific fertilization of hamster eggs. The analysis of these aberrations shows that while in controls only 9.4% of structural abnormalities are of the stable type, in treated patients this figure increases to 39.3%, thus indicating that the anomalies have not been produced during the fertilization of the hamster egg. However, it is possible that part, or even most, of the breaks appear as a result of a reduced repair capacity of sperm chromosomes in the cytoplasm of the hamster egg.     

Variation in the frequencies of spontaneous and in vitro induced chromosome aberrations in human lymphocytes during natural and radiation-induced aging

The frequency of translocations detected by FISH in lymphocytes of control donors increases with age as a quadratic function. This process is faster in persons previously exposed to low doses of radiation. It means that translocation frequency can be used as a measure of biological age. Moreover, translocation frequency should be taken into account in biological reconstruction of absorbed doses. The frequencies of dicentrics detected by FIGH and FPG linearly increase with age in both groups, and this process occurs at equal rates during natural and radiation-induced aging. The age-dependent increase in the frequency of translocations exceeds the increase in dicentrics. The radiation sensitivity of lymphocytes estimated from the frequency of in vitro induced chromosomal aberrations tends to increase with age in the control group and decreases significantly in the group exposed to radiation; i.e., low-dose preexposure alters the pattern of the age dependence of radiation sensitivity in lymphocytes in vitro.     

Radiation-induced chromosome aberrations in guinea-pig growing oocytes, and their relation to follicular atresia

The female guinea-pig has been shown to represent a good model to investigate the genetic hazard of ionizing radiation in humans. The sensitivity of the guinea-pig oocytes to radiation-induced chromosome aberrations was, therefore, studied at different stages of oocyte and follicular growth. The sensitivity of oocytes enclosed in small follicles (15 weeks before ovulation) was found to be low and comparable to that of immature oocytes present at birth. The sensitivity of growing oocytes remained low and almost constant until 3 weeks before ovulation, from which time it began to increase. The most dramatic increase of sensitivity occurred during the last week preceding ovulation: about 90% of oocytes X-irradiated with 4Gy, 2 days before ovulation showed one or more chromatid interchanges, as compared to 20% for those irradiated with the same dose 1 week earlier. A comparison of our results with those found by others in the mouse shows that considerable differences of sensitivity exist between oocytes of these two species irradiated at similar stages of development. The possible reasons for these differences are discussed.     

Recovery kinetics of radiation-induced chromosome aberrations in human G0 lymphocytes

Summary Declining yields of radiation-induced dicentric chromosomes in human G⁰ lymphocytes were observed in split-dose experiments with time intervals varied up to 8 h. In agreement with microdosimetric intratrack-intertrack interaction models, only the dose-squared yield component was reduced and approached an asymptotic value equal to one half of the corresponding single exposure yield. For 150 kV X-rays and 13 MeV electrons, at total doses up to 6 Gy, the time constant of the approximately exponential decline was practically dose- and quality-independent within a range of 100–180 min. For 10 kV X-rays, in the presence of a dominant linear yield component, only a small split-dose effect, but with a consistent-value, was observed for a total dose of 5 Gy. Since can be interpreted as the mean life time of primary lesions in chromatin fibres, its independence from absorbed dose and radiation quality means that radiation damage of the split-dose recovery mechanism can be excluded for doses up to 6 Gy. By correlating the observed split-dose reduction of the acentric fragment yield to the reduction of the dicentric yield, (1.64 ± 0.03) acentrics/dicentric for 150 kV X-rays and (1.51 ± 0.11) acentrics/dicentric for 13 MeV electrons were obtained. Acentrics formed in the course of dicentric formation as well as in other binary interactions of primary lesions are represented in these ratios. Post-irradiation recovery during time intervals between irradiation and cell stimulation up to 24 h did not occur. The relations to comparable results in cell lethality experiments are discussed, and a hypothesis of fast and slow binary interactions of primary lesions is put forward.Dedicated to Prof. Dr. H. Muth on the occasion of his 65th birthdayThis work was supported by the Bundesministerium des Innern, Bonn, FRG