Infant leukaemia after the Chernobyl accident.
Explore the source record for details and available documents.
Child, Preschool↗
Biomedical subjects
W Burkart
Publications and source records attributed to W Burkart.
Down syndrome clusters in Germany after the Chernobyl accident.
In two independent studies using different approaches and covering West Berlin and Bavaria, respectively, highly significant temporal clusters of Down syndrome were found. Both sharp increases occurred in areas receiving relatively low Chernobyl fallout and concomitant radiation exposures. Only for the Berlin cluster was fallout present at the time of the affected meioses, whereas the Nuremberg cluster preceded the radioactive contamination by 1 month. Hypotheses on possible causal relationships are compared. Radiation from the Chernobyl accident is an unlikely factor, because the associated cumulative dose was so low in comparison with natural background. Microdosimetric considerations would indicate that fewer than 1 in 200 oocyte nuclei would have experienced an ionizing event from Chernobyl radioactivity. Given the lack of understanding of what causes Down syndrome, other than factors associated with increased maternal age, additional research into environmental and infectious risk factors is warranted.
Down Syndrome↗
Enhanced neoplastic transformation in an inhomogeneous radiation field: an effect of the presence of heavily damaged cells.
In the inhomogeneous radiation field surrounding small beta-particle sources, nonlethally and heavily damaged cells are in proximity, permitting interaction via extracellular signals. This situation is typical of hot particles such as those released during the accident at Chernobyl. Beta-particle-emitting yttrium-90 wires (average energy 934 keV) were employed to investigate radiation-induced neoplastic transformation under these conditions. Integrated 24-h doses ranging from 0 to 750 Gy across the exposure field were applied. At equal levels of toxicity a 10-fold enhancement of neoplastic transformation frequency in C3H 10T1/2 cells was observed in the presence of heavily damaged cells. Homogeneous fields of low-dose-rate beta-particle radiation produced neoplastic transformation frequencies typical for comparable photon exposures reported in the literature.
Animals↗
Human cytogenetic consequences of the Chernobyl accident.
The frequency of chromosomal aberrations was evaluated in more than 500 liquidators of the Chernobyl accident. The 'sarcophagus' builders and the dosimetrists showed the highest frequency of aberrations per 100 cells: 3.24 +/- 0.25 and 3.11 +/- 0.43. For Chernobyl Atomic Power Station staff members the mean frequencies of aberrations per 100 cells was 2.37 +/- 0.20. The mean yields of aberrations in the other groups was between 1.31 and 1.47 per 100 cells. If the mean frequencies of aberrations are converted into equivalent whole body doses, values between 136 and 414 mGy are obtained. Especially in the group of 'sarcophagus' builders, the yields of aberrations varied interindividually and corresponded to equivalent whole body doses of up to about 2 Gy.
Chromosome Aberrations↗
Radioepidemiology in the aftermath of the nuclear program of the former Soviet Union: unique lessons to be learnt.
The military and civilian nuclear activities in the former Soviet Union led to unique exposures and resulted in high cumulative doses in several populations. In comparison to the atomic bomb survivors, at present the most important cohort in radiation epidemiology, collective and individual doses received by early workers in the plutonium production facilities at Mayak (Chelyabinsk). Techa River residents downstream of Mayak, populations downwind of the Semipalatinsk test site, and subpopulations of Chernobyl victims surpass the Hiroshima/Nagasaki experience in most cases. Even more importantly, the dose rates cover the full range of exposures relevant for radiation protection. i.e., acute to year-long chronic exposures from environmental contamination and bone seeking radionuclides. Parallel to the humanitarian need to mitigate health effects from these exposures, the unique opportunities for research on radiation risks related to low dose rate and chronic radiation have to be explored. Increased efforts by the global radiation research community are needed to address the many questions which cannot be answered by the acutely irradiated survivors of Hiroshima/Nagasaki. Specific attention needs to be drawn to the validation of available exposure and health records and to dose reconstruction which must include dietary sources of exposure. Preliminary intercomparison and validation exercises indicate potentially large sources of error, e.g., due to uncertainties in the reconstruction of early exposures and effects and due to continuing incorporation.
Dose-Response Relationship, Radiation↗
Effects of ionizing- and UV B-radiation on proteins controlling cell cycle progression in human cells: comparison of the MCF-7 adenocarcinoma and the SCL-2 squamous cell carcinoma cell line.
MCF-7 and SCL-2 cells were irradiated with UV B-radiation or with 137Cs gamma-radiation, in order to investigate cell cycle checkpoint control mechanisms. Effects of both qualities of radiation were investigated for the two cell lines in regard to p53 protein levels, and alterations in Cdk1 (cyclin dependent kinase 1) and Cdk2 phosphorylation were monitored. SCL-2 cells constitutively overexpressed a form of p53 protein whose abundance remained unchanged after irradiation, whereas MCF-7 cells expressed wild type p53 whose abundance increased after irradiation. Accordingly, MCF-7 cells showed a strong G1 phase arrest, whereas SCL-2 cells were only delayed in S phase (after UV B-irradiation) and arrested in G2 phase (after gamma-irradiation and UV B-irradiation), as monitored by flow cytometry. In MCF-7 cells increased p53 levels were observed for up to 30 h after gamma-irradiation and up to 20 h after UV B-irradiation. Only in SCL-2 cells was there a significant radiation induced inactivation of Cdk1 by hyperphosphorylation. This effect was prevented by culturing cells in the presence of caffeine after irradiation. After UV B-irradiation the inactivation of Cdk1 was less pronounced and only partially diminished in the presence of caffeine. No alteration in Cdk2 phosphorylation was observed after irradiation in either cell line.
Adenocarcinoma↗
UV-B-induced cell cycle perturbations, micronucleus induction, and modulation by caffeine in human keratinocytes.
UV-B-induced perturbations of cell cycle progression in asynchronous human keratinocytes were analysed during two cell cycles with respect to their cell cycle stage at the time of irradiation using BrdUrd/Hoechst flow cytometry. Exponentially growing SCL-2-keratinocytes exposed to UV-B radiation showed a short delay in G1-phase exit and were blocked in the S and G2/M phases of the first cell cycle. UV-A wavelengths did not show any detectable effect on cell cycle progression. In contrast, 137Cs-irradiation of these cells induced a temporary G2 block only. Micronucleus frequency increased in gamma-irradiated cells as soon as the cells started to divide and reached a plateau when most of the cells had divided. Continuous treatment with caffeine starting immediately after 137Cs gamma-irradiation prevented accumulation of cells in G2 phase, but did not influence the frequency of micronuclei. In UV-B-irradiated keratinocytes, however, the damage-induced cell cycle perturbations were merely reduced by caffeine, but not eliminated. Compared with gamma-irradiation a moderate induction of micronuclei was observed in UV-B-irradiated cells. Caffeine, however, potentiated the induction of micronuclei by UV-B. These different effects on cell cycle kinetics and micronucleus induction indicate different mechanisms of DNA damage caused by UV-B- and gamma-irradiation that may be repaired through different pathways.
Caffeine↗
A pure beta line source to assess hot particle effects in vitro.
A model system is presented for assessing the biological effects of inhomogeneous irradiation fields resulting from exposure to particulate radioactive matter (hot particles). The resulting harm per unit dose to tissue is qualitatively different from homogeneous irradiation sources because of specific hot particle effects such as wasting of dose to necrotic tissue (overkill) and formation of microlesions leading to growth stimulation in adjacent tissue. In the case of beta-emitters, many of the cells in adjacent tissue receive considerable sublethal doses. To assess the influence of local necrosis and growth stimulation on radiation transformation in vitro, a neutron activated short 90Y wire was attached to the bottom foil of a cell culture dish. The system achieves doses of up to 200 Gy h(-1) directly above the wire, rapidly falling off within a few mm to less than 0.5 Gy h(-1). Acute cell death of murine M3-1 cells was observed in the highest dose regions. Colony-forming ability as a function of distance from the wire was investigated. The surviving fraction decreased over several orders of magnitude between 3 and 10 mm from the wire. This report describes the physical characteristics of the model system and subsequent biological survival data for mammalian cell culture. It is a useful and versatile system for modeling inhomogeneous radiation field effects.
Animals↗
First attempts at validation of radiation exposure of the population along the Techa River, southern Urals.
A research programme sponsored by the German Federal Ministry for the Environment, Nature Protection and Nuclear Safety (BMU) was conducted during 1992 and 1993 in the Southern Urals, to provide an initial validation and comparison of results of population exposure arising from the release of radioactive waste from the MAYAK nuclear facility between the years 1948 and 1967. This programme included investigations of the contamination of the soil, of food (milk, drinking-water, potatoes) and whole-body-counter measurements of inhabitants of settlements at the Techa River. The nuclides of interest were plutonium isotopes and the long-lived fission products 137Cs and 90Sr. Results of these investigations, particularly in and around the village of Muslyumovo (78 km downstream from the point of release of the radioactive waste into the Techa River), are shown. These investigations are a first step towards an independent validation of the enormous data base collected by the Russian institutes and of derived values of the doses to the population of the Techa River.
Environmental Exposure↗
Resolution of DNA damage at the single-cell level shows largely different actions of X-rays and bleomycin.
Both X-rays and the radiomimetic agent bleomycin (BLM) induce DNA strand breaks, predominantly via reactive radicals. To compare the induction of breaks with the two agents in Chinese hamster (CHO-K1) cells, two different alkaline unwinding methods, a 3H tracer-based analysis of large cell populations and an optical adaption allowing measurement of single cells, were applied. Radiation and BLM show qualitatively similar dose responses when the average number of DNA strand breaks is measured in a large cell population. However, the breakage pattern at the single-cell level indicates large discrepancies between the actions of the two agents. Irradiated cells show a uniform distribution of DNA strand breaks over the cell population. Effects of treatment with 30 micrograms x ml-1 BLM for 2 hr vary from practically zero in some cells to high levels of DNA strand breakage in others. Unlike the repair of radiation-induced DNA breaks, the repair efficiency of BLM-induced DNA strand breaks, as measured at the single-cell level, varies strongly among cells of the same population. Such heterogeneity at the cellular level potentially reduces BLM's usefulness for tumor therapy because the appearance of BLM-resistant subpopulations may critically impair treatment outcome.
Animals↗
Caffeine release of radiation induced S and G2 phase arrest in V79 hamster cells: increase of histone messenger RNA levels and p34cdc2 activation.
The serine/threonine protein kinase p34cdc2 activity in V79 hamster cells 4 h after treatment with 7-Gy X-rays is similar to that of unirradiated cells. Nevertheless, the irradiated cells are arrested in the S and G2 phases of the cell cycle. The mRNA concentrations of histones H1 and H4 are reduced by a factor of about 2 in irradiated cells compared to unirradiated cells, as opposed to the mRNAs of high-mobility group I(Y) and 17 proteins which appear unchanged. Both the p34cdc2 activity and the mRNA concentrations of the histones rise within 30 min after the release of the radiation induced cell cycle block by caffeine. During this time span the p34cdc2 activity increases about 4-fold and the histone mRNA levels recover approximately to those of an exponentially growing cell population. Regulatory pathways influenced in irradiated and in subsequently caffeine treated cells apparently interact with basic cell cycle control mechanisms.
Animals↗
Staurosporine- and radiation-induced G2-phase cell cycle blocks are equally released by caffeine.
We show here that the arrests of cells in G2 phase of the cell cycle induced by either staurosporine or ionizing radiation are closely related phenomena governed by a common kinase signaling pathway. The protein kinase inhibitor staurosporine induces a complete G2-phase arrest in exponentially growing TK6 human lymphoblastoid and V79 Chinese hamster fibroblast cells. Both cell types are equally sensitive to the kinase inhibitor and the arrest is dependent on its continued presence. Caffeine completely abrogates this arrest at concentrations comparable to those which abrogate radiation-induced G2-phase arrest. The kinetics of caffeine-induced release of both kinds of arrest are essentially identical. The activity of p34cdc2 kinase was also found to increase in a parallel fashion after caffeine-induced release of both kinds of arrest. As opposed to those transformed cell types which arrest only in G2 phase in response to staurosporine, immortalized C3H 10T1/2 fibroblasts and Muntjak skin fibroblasts display both G1- and G2-phase arrests. The results suggest that staurosporine and radiation interact with regulatory pathways in the cell cycle, and specifically with a caffeine-sensitive signal transduction pathway which recognizes DNA damage, regulates the G2/M-phase transition, and attenuates the biological consequences of radiation exposure.
Alkaloids↗
Assessment of radiation-induced DNA strand breaks and their repair in unlabeled cells.
Radiation induced damage, i.e., the induction of DNA strand breaks, was studied on the level of single, unlabeled cells. DNA strand breaks were determined by direct partial alkaline unwinding in intact cell nuclei followed by staining with acridine orange, a development of a proposal first described by B. Rydberg (Int J Radiat Biol 46:521-527, 1984). The ratio of green fluorescence (double-stranded DNA) to red fluorescence (single-stranded DNA) in single cells was taken as a measure of DNA strand breaks. CHO-K1 and M3-1 cells irradiated with X-rays show a dose dependent induction of DNA strand breaks. Incubation at 37 degrees C after irradiation leads to repair of breaks. A repair halflife of about 10-11 min can be determined. Cell cycle specific differences in the induction of DNA strand breaks or repair behavior are not detectable at the resolution achieved so far. This new method offers two major advantages: the resolution of DNA damage and repair on the level of single cells and no need for labeling, thereby allowing for DNA damage and repair to be assessed in biopsy material from tumor patients.
Acridine Orange↗
Lack of adaptive response to low doses of ionizing radiation in human lymphocytes from five different donors.
Various investigators reported a reduced yield of chromosome and chromatid aberrations in short-term cultures of human lymphocytes if a 'challenge' exposure to ionizing radiation was preceded by an 'adaptive' exposure. In order to examine the cell cycle dependence of the 'adaptive response', chromosome and chromatid aberration yields were estimated after challenge doses in the G1, S or G2 phase of lymphocytes which had been adapted in the early G1 phase. On testing two donors no protective adaptive response was found. Blood samples of four donors were tested for their capability to evoke the adaptive response in a standard experiment with the adaptive dose in the S phase and the challenge dose in the G2 phase. A synergistic response occurred in one out of two similar experiments performed with the same blood sample. The three other blood samples tested did not respond. Apparently these data indicate a high frequency of human lymphocyte cultures that do not display an adaptive response.
Adaptation, Physiological↗
From energy deposition to cancer.
Recent progress in molecular biology, genetics and microdosimetry has considerably increased our knowledge of the mechanisms of radiation-induced carcinogenesis. However, as a result of the complexities involved in the many genetic and epigenetic changes in cells leading to the expression of malignancy only years or even decades after radiation exposure, risk coefficients for the quantification of health detriment still have to be derived largely from epidemiological data and animal studies. On the other hand, improved understanding of molecular and cellular mechanisms is increasingly important in testing and refuting hypotheses about the relative carcinogenic potential of different radiation qualities and dose rates, and of low-level exposures.
Adaptation, Biological↗
Lung cancer and alpha radiation.
The considerable radiosensitivity of the human lung together with the highly localized alpha-doses in the bronchial and pulmonary regions from naturally occurring and man-enhanced radon decay products make the respiratory tract the most critical organ for cancer from exposure to ionizing radiation in our environment. From indoor radon, the tracheobronchial region of the lung generally receives radiation doses which are at least an order of magnitude above the total dose to any other organ. Excess lung cancer deaths found in epidemiological studies on heavily exposed populations of miners can be fitted reasonably well to a relative risk model, when declines in relative risk with both age at risk evaluation, and time since exposure, are incorporated. Smoking seems to act synergistically. A comparison of the major radon risk projections shows considerable discrepancies in the best estimates of risk, indicating that the uncertainties remain large.
Adolescent↗
In-process controls and characterization of recombinate antihemophilic factor (recombinant).
Explore the source record for details and available documents.
Antibodies, Monoclonal↗
Dynamics of Rn transport from the cellar to the living area in an unheated house.
Environmental parameters such as temperature and wind, occupant activities, and house-specific parameters such as subsoil geology, leakiness of the substructure to soil gas, and air exchange rate are the main factors influencing Rn entry into a building and its subsequent indoor behavior. Experiments performed in an unheated, uninhabited house showed a reproducible diurnal fluctuation of the indoor concentration of Rn decay products. Strong, long-term correlations between temperature differences indoor-outdoor (indoor temperature minus outdoor temperature) and pressure differences outdoor-indoor (outdoor pressure minus indoor pressure) were found. At positive temperature differences inside-outside, an average airflow velocity of about 0.05 m s-1 between ground floor and first floor was detected. This air movement was able to vertically transport Rn at a rate of approximately 11 kBq h-1 in a volume of air of about 5.5 m3 through a cross-sectional area of only 0.03 m2. For this specific house, stack effects were identified as the main driving force for Rn migration from the cellular to higher floors. The diurnal fluctuation of Rn progeny concentrations in the living area can be explained by temporal variations in the amount of Rn-rich air transported vertically from the cellar into the building as a consequence of stack effects.
Air Pollutants, Radioactive↗