88 results on '"Müller WU"'
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2. Sind einige Millisievert schon gefährlich? Wirkung von Röntgenstrahlen auf Zelle und Organismus im Niedrigdosisbereich
- Author
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Müller, WU, primary
- Published
- 2008
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3. Deterministische und stochastische Strahlenschäden
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Müller, WU, primary
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- 2008
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4. Prenatal radiation exposure in diagnostic and interventional radiology.
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Fiebich M, Block A, Borowski M, Geworski L, Happel C, Kamp A, Lenzen H, Mahnken AH, Müller WU, Östreicher G, Rudolf F, Stamm G, Starck P, Steiniger B, Wicke JH, Wolf U, Wucherer M, Zankl M, Zink K, and Zweig C
- Subjects
- Dose-Response Relationship, Radiation, Female, Humans, Pregnancy, Radiation Exposure analysis, Fetus radiation effects, Radiation Dosage, Radiation Exposure adverse effects, Radiology, Interventional
- Abstract
Background: The exposure of a pregnant woman to X-rays is an event that can cause uncertainty for all concerned. This review provides guidance on how to assess such a situation and how to determine the dose to the unborn child. In general, the use of X-rays in pregnant women in radiology should be avoided. If possible, alternatives should be used, or examinations postponed to a time after the pregnancy. This review gives a summary of the procedure for determining the radiation exposure of a pregnant woman., Method: Based on the previous report of 2002 and the literature on prenatal radiation exposure published thereafter, the DGMP/DRG report on the procedure for the assessment of prenatal radiation exposure was adapted to the current state of science and technology., Results: Typically, only relatively low radiation exposures of less than 20 mSv occur for the unborn child in X-ray diagnostics in the vast majority of cases. At these dose level the additional risk of damage to the embryo or fetus caused by the radiation is low and therefore only a rough conservative estimate using tabulated values are made. Only in a few types of examination (CT and interventional radiology) higher doses values might occur in the uterus. Instead of dose estimates (step 1 in the two-step model) in these cases the calculation of dose (step 2) are required and further action by the physician may be necessary., Conclusions: During the assessment, it is useful to initially use simple conservative estimation procedures to quickly determine whether a case falls into this large group less than 20 mSv, where there is a very low risk to the unborn child. If this is the case, the pregnant woman should be informed immediately by the doctor who performed the examination/treatment. This avoids a psychological burden on the patient. The DGMP/DRG report suggests a relatively simple, clearly structured procedure with advantages for all parties involved (physician, medical physics experts, MTRA and patient)., Key Points: · The DGMP/DRG report on prenatal radiation exposure describes the procedure for calculating radiation exposures and the associated risks for the unborn child.. · Using the two-step model, only a simple assessment based on the first step is necessary for most prenatal radiation exposures.. · With the given tables it is possible to estimate individual risks for the unborn child taking into account the radiation exposure.. · Only in the rare case that the first estimate results in a uterine dose larger 20 mSv a more accurate calculation is necessary.., Citation Format: · Fiebich M, Block A, Borowski M et al. Prenatal radiation exposure in diagnostic and interventional radiology. Fortschr Röntgenstr 2021; 193: 778 - 786., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)
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- 2021
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5. Dose limits for occupational exposure to ionising radiation and genotoxic carcinogens: a German perspective.
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Rühm W, Breckow J, Dietze G, Friedl A, Greinert R, Jacob P, Kistinger S, Michel R, Müller WU, Otten H, Streffer C, and Weiss W
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- Animals, Germany, Humans, Radiation Protection methods, Radiation Protection standards, Carcinogens, Occupational Exposure standards, Radiation Dosage, Radiation Exposure standards, Radiation, Ionizing
- Abstract
This paper summarises the view of the German Commission on Radiological Protection ("Strahlenschutzkommission", SSK) on the rationale behind the currently valid dose limits and dose constraints for workers recommended by the International Commission on Radiological Protection (ICRP). The paper includes a discussion of the reasoning behind current dose limits followed by a discussion of the detriment used by ICRP as a measure for stochastic health effects. Studies on radiation-induced cancer are reviewed because this endpoint represents the most important contribution to detriment. Recent findings on radiation-induced circulatory disease that are currently not included in detriment calculation are also reviewed. It appeared that for detriment calculations the contribution of circulatory diseases plays only a secondary role, although the uncertainties involved in their risk estimates are considerable. These discussions are complemented by a review of the procedures currently in use in Germany, or in discussion elsewhere, to define limits for genotoxic carcinogens. To put these concepts in perspective, actual occupational radiation exposures are exemplified with data from Germany, for the year 2012, and regulations in Germany are compared to the recommendations issued by ICRP. Conclusions include, among others, considerations on radiation protection concepts currently in use and recommendations of the SSK on the limitation of annual effective dose and effective dose cumulated over a whole working life.
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- 2020
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6. Current knowledge on radon risk: implications for practical radiation protection? radon workshop, 1/2 December 2015, Bonn, BMUB (Bundesministerium für Umwelt, Naturschutz, Bau und Reaktorsicherheit; Federal Ministry for the Environment, Nature Conservation, Building and Nuclear Safety).
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Müller WU, Giussani A, Rühm W, Lecomte JF, Harrison J, Kreuzer M, Sobotzki C, and Breckow J
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- Humans, Radiation Dosage, Radiation Exposure, Radiation Protection, Risk, Air Pollutants, Radioactive, Radon
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ICRP suggested a strategy based on the distinction between a protection approach for dwellings and one for workplaces in the previous recommendations on radon. Now, the Commission recommends an integrated approach for the protection against radon exposure in all buildings irrespective of their purpose and the status of their occupants. The strategy of protection in buildings, implemented through a national action plan, is based on the application of the optimisation principle below a derived reference level in concentration (maximum 300 Bq m(-3)). A problem, however, arises that due to new epidemiological findings and application of dosimetric models, ICRP 115 (Ann ICRP 40, 2010) presents nominal probability coefficients for radon exposure that are approximately by a factor of 2 larger than in the former recommendations of ICRP 65 (Ann ICRP 23, 1993). On the basis of the so-called epidemiological approach and the dosimetric approach, the doubling of risk per unit exposure is represented by a doubling of the dose coefficients, while the risk coefficient of ICRP 103 (2007) remains unchanged. Thus, an identical given radon exposure situation with the new dose coefficients would result in a doubling of dose compared with the former values. This is of serious conceptual implications. A possible solution of this problem was presented during the workshop.
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- 2016
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7. Current discussions of DDREF, cataracts, circulatory diseases and dose limits.
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Müller WU
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- Animals, Cataract etiology, Dose-Response Relationship, Radiation, Europe, Evidence-Based Medicine, Humans, Maximum Allowable Concentration, Radiation Dosage, Radiation Exposure adverse effects, Radiation Injuries etiology, Radiation Monitoring, Vascular Diseases etiology, Cataract prevention & control, Models, Biological, Radiation Exposure analysis, Radiation Injuries prevention & control, Radiation Protection methods, Vascular Diseases prevention & control
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Although more than a century of radiation research has provided a lot of insight into radiation risk, there are still fields that need clarification. This is particularly true for the low dose range, meaning doses up to ∼100 mSv. One can detect biological effects in that dose range, but it is unclear whether these biological effects like mutations or chromosomal aberrations translate into health effects like cancer, cataracts or circulatory diseases. Thus, for radiation protection purposes, assumptions have to made that must be reappraised on the basis of new findings from time to time. Affected by new insights are currently the DDREF (dose and dose-rate effectiveness factor), cataracts and circulatory diseases. If the new findings are very convincing, dose limits have to be changed at short notice. If there are only weak indications, stability of the radiation protection system is more important than changing limits all the time., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
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- 2015
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8. Individual variations in the micronucleus assay for biological dosimetry after high dose exposure.
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Kacprzak J, Kuszewski T, Lankoff A, Müller WU, Wojcik A, and Lisowska H
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- Adult, Cells, Cultured, Cobalt Radioisotopes, Dose-Response Relationship, Radiation, Female, Humans, Lymphocytes cytology, Male, Micronucleus Tests, Young Adult, Cell Proliferation radiation effects, Gamma Rays adverse effects, Leukocytes, Mononuclear radiation effects, Lymphocytes radiation effects, Manganese analysis, Micronuclei, Chromosome-Defective radiation effects, Radiometry
- Abstract
The micronucleus assay is widely used as a biological dosimeter. Due to an inhibitory effect of radiation on cell proliferation the assay yields satisfactory results only when the absorbed dose is below about 5Gy. In 2002 Müller and Rode suggested that a modified version of the test, based on the analysis of the ratio of trinucleated to tetranucleated cells and the frequency of micronuclei (Mn) in binucleated cells containing at least one Mn, can be applied to detect a dose reaching 15Gy (Mutat. Res. 502 (2002) 47-51). Their conclusion was based on the results of experiments with lymphocytes from one donor and nothing is known about the possible influence of individual variability on the applicability of the Mn test to detect high doses of radiation. The aim of the present study was to validate the modified micronucleus assay with lymphocytes of 5 donors. Their blood was exposed to 0, 5, 10, 15 and 20Gy of (60)Co gamma rays. The levels of Mn and of cell proliferation were assessed using various approaches. A strong inter-individual variability was observed for all endpoints. The results clearly show that the assessment of cell proliferation is essential for the interpretation of results. Unfortunately, it was not possible to identify one single proliferation marker that gives all necessary information., (Copyright © 2013 Elsevier B.V. All rights reserved.)
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- 2013
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9. [Agencies for radiation protection in Germany, Europe and worldwide. Responsibilities and relations between].
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Müller WU
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- Europe, Internationality, Interinstitutional Relations, Nuclear Medicine organization & administration, Practice Guidelines as Topic, Radiation Protection standards, Radiopharmaceuticals standards, Safety Management organization & administration
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The complex radiation protection system is affected by various organisations. The most important bodies worldwide, in Europe and in Germany will be introduced including a description of their relationships. Three levels of responsibility have to be discriminated: the scientific, the philosophical/methodical, and the level of jurisdiction and regulations.
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- 2013
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10. Clinical, molecular- and cytogenetic analysis of a case of severe radio-sensitivity.
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Greulich-Bode KM, Zimmermann F, Müller WU, Pakisch B, Molls M, and Würschmidt F
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In radiotherapy the normal tissue reaction is often a limiting factor for radiation treatment. Still there is no screening method, which predicts normal tissue reaction on radiotherapy, especially in comparison to tumor tissue, and therefore allows tailoring of the radiation dose to each patient. Here, we present a case of severe radiation-related side effects. We applied classical cytogenetic techniques (Giemsa-banding and staining of centromeric regions), the comet assay as well as multicolor fluorescence in situ hybridization on peripheral blood lymphocytes of this patient in order to determine the radio-sensitivity on the DNA level and to correlate these findings with the clinical outcome. Our investigations revealed abnormalities on chromosome 9, deficiencies in the DNA-repair capacity after radiation exposure and a high number of radiation induced chromosomal aberrations. A detected high amount of residual damage two or three hours after radiation exposure and repair as well as the high number of chromosomal aberrations (ChAs) suggests a correlation between repair capacity and radiation induced ChAs. We concluded that the detected abnormalities might serve as a genetic basis for the radio-sensitive phenotype of this patient. Taken together this report strengthens the idea that intensive DNA genomic analysis of individual patients can serve as the basis for more favourable treatment of cancer patients.
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- 2012
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11. In vivo versus in vitro individual radiosensitivity analysed in healthy donors and in prostate cancer patients with and without severe side effects after radiotherapy.
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Brzozowska K, Pinkawa M, Eble MJ, Müller WU, Wojcik A, Kriehuber R, and Schmitz S
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- Aged, Aged, 80 and over, Apoptosis radiation effects, Chromatids genetics, Chromatids radiation effects, Chromosome Aberrations radiation effects, G2 Phase radiation effects, Histones metabolism, Humans, Male, Middle Aged, Prostatic Neoplasms genetics, Prostatic Neoplasms metabolism, Health, Prostatic Neoplasms pathology, Prostatic Neoplasms radiotherapy, Radiation Tolerance genetics, Radiation Tolerance radiation effects, Radiotherapy, Conformal adverse effects
- Abstract
Background: A high cellular radiosensitivity may be connected with a risk for development of severe side effects after radiotherapy and indicate cancer susceptibility. Hence, a fast and robust in vitro test is desirable to identify radiosensitive individuals., Materials and Methods: The study included 25 prostate cancer patients with severe side effects (S) and 25 patients without severe side effects (0) after radiotherapy as well as 23 male healthy age-matched donors. Blood samples were exposed to 0.5 Gy or 1 Gy of γ-rays. The initial level of double-strand breaks (dsb) and repair kinetics measured by phosphorylation of histone H2A (γ-H2AX-assay), apoptosis (Annexin V-assay) and the induction of chromatid aberrations after irradiation in the G2-phase of the cell cycle (G2-assay) were analysed., Results: A significant higher chromatid aberration yield was found in lymphocytes from prostate cancer patients when compared to healthy donors. We found no significant differences between patients S and patients 0., Conclusions: There is no obvious correlation between clinical and cellular radiosensitivity in lymphocytes of prostate cancer patients when all chosen in vitro assays are considered. Although 25% of the patients showed both severe side effects and increased radiation-induced chromosomal sensitivity, predictive value of G2-assay is doubtful.
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- 2012
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12. Radiation exposure during pregnancy.
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Raabe A and Müller WU
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- Adult, Counseling, Dose-Response Relationship, Radiation, Female, Gestational Age, Humans, Neoplasms, Radiation-Induced epidemiology, Pregnancy, Pregnancy Complications, Cardiovascular surgery, Risk Assessment, Subarachnoid Hemorrhage diagnostic imaging, Subarachnoid Hemorrhage surgery, Tomography, X-Ray Computed, Fetus radiation effects, Pregnancy Complications, Cardiovascular diagnostic imaging
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- 2008
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13. Comment on the invited editorial 'Effectiveness of tritium beta particles'.
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Müller WU
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- Animals, Humans, Neoplasms, Radiation-Induced prevention & control, Relative Biological Effectiveness, Risk Assessment, Risk Factors, Beta Particles, Environmental Exposure, Radiation Protection, Tritium
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- 2008
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14. Single and repeated moderate consumption of native or dealcoholized red wine show different effects on antioxidant parameters in blood and DNA strand breaks in peripheral leukocytes in healthy volunteers: a randomized controlled trial (ISRCTN68505294).
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Arendt BM, Ellinger S, Kekic K, Geus L, Fimmers R, Spengler U, Müller WU, and Goerlich R
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- Adolescent, Adult, Antioxidants analysis, Comet Assay, Female, Flavonoids analysis, Humans, Hydrogen Peroxide pharmacology, Male, Middle Aged, Phenols analysis, Polyphenols, Prospective Studies, Antioxidants administration & dosage, DNA Damage drug effects, Ethanol analysis, Flavonoids administration & dosage, Leukocytes chemistry, Phenols administration & dosage, Wine analysis
- Abstract
Background: Red wine (RW) is rich in antioxidant polyphenols that might protect from oxidative stress related diseases, such as cardiovascular disease and cancer. Antioxidant effects after single ingestion of RW or dealcoholized RW (DRW) have been observed in several studies, but results after regular consumption are contradictory. Thus, we examined if single or repeated consumption of moderate amounts of RW or DRW exert antioxidant activity in vivo., Methods: Total phenolic content and concentration of other antioxidants in plasma/serum, total antioxidant capacity (TEAC) in plasma as well as DNA strand breaks in peripheral leukocytes were measured in healthy non-smokers A) before, 90 and 360 min after ingestion of one glass of RW, DRW or water; B) before and after consumption of one glass of RW or DRW daily for 6 weeks. DNA strand breaks (SB) were determined by single cell gel electrophoresis (Comet Assay) in untreated cells and after induction of oxidative stress ex vivo with H2O2 (300 microM, 20 min)., Results: Both RW and DRW transiently increased total phenolic content in plasma after single consumption, but only RW lead to a sustained increase if consumed regularly. Plasma antioxidant capacity was not affected by single or regular consumption of RW or DRW. Effects of RW and DRW on DNA SB were conflicting. DNA strand breaks in untreated cells increased after a single dose of RW and DRW, whereas H2O2 induced SB were reduced after DRW. In contrast, regular RW consumption reduced SB in untreated cells but did not affect H2O2 induced SB., Conclusion: The results suggest that consumption of both RW and DRW leads to an accumulation of phenolic compounds in plasma without increasing plasma antioxidant capacity. Red wine and DRW seem to affect the occurrence of DNA strand breaks, but this cannot be referred to antioxidant effects.
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- 2005
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15. Analysis of the action of the restriction endonuclease AluI using three different comet assay protocols.
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Müller WU, Ciborovius J, Bauch T, Johannes C, Schunck C, Mallek U, Böcker W, Obe G, and Streffer C
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- Animals, CHO Cells, Cells, Cultured, Cricetinae, Cricetulus, DNA Restriction Enzymes pharmacology, Dose-Response Relationship, Drug, Dose-Response Relationship, Radiation, Female, Humans, Male, Middle Aged, Radiation Dosage, Reproducibility of Results, Sensitivity and Specificity, X-Rays, Comet Assay methods, DNA drug effects, DNA radiation effects, DNA Damage, Deoxyribonucleases, Type II Site-Specific administration & dosage, Lymphocytes drug effects, Lymphocytes radiation effects
- Abstract
Background and Purpose: The comet assay offers the opportunity to measure the amount of DNA damage and the effectiveness of DNA repair in single cells. In a first part, experiments are presented comparing three different protocols of the comet assay technique with respect to the analysis of the induction of DNA damage after X-irradiation in isolated human lymphocytes and CHO cells. In a second part, the restriction enzyme AluI, an agent producing DNA double-strand breaks exclusively, was introduced into CHO cells by electroporation and the effects were analyzed using the different comet assay protocols. The experiments were carried out in order to test the assertion that comet assay techniques can measure different types of DNA damages at different pH conditions of lysis and electrophoresis., Material and Methods: Three different comet assay protocols were used for the analysis of DNA damage in lymphocytes and CHO cells., Results: The results clearly indicate that among the three protocols the modified comet assay technique used by the authors showed the highest sensitivity in the radiotherapy-relevant dose range between 0 and 2 Gy. All three protocols were capable of detecting an effect by AluI. This effect, however, was clearly different from radiation effects. Whereas after radiation exposure all cell nuclei show a dose-dependent increase in DNA content in the comet tail, most of the cell nuclei were unaffected by an AluI uptake. Nevertheless, there was an effect by AluI that could be detected in all three assay versions: between 5% and 15% of the nuclei showed clearly abnormal comet morphologies., Conclusion: Neither the strictly alkaline nor the strictly neutral comet assay is applicable in the radiation dose range of about 2 Gy. The restriction enzyme results show that other factors than just DNA strand breaks contribute to DNA migration into the tail of the comets.
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- 2004
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16. Micronucleus formation in lymphocytes of children from the vicinity of Chernobyl after (131)I therapy.
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Müller WU, Dietl S, Wuttke K, Reiners C, Biko J, Demidchik E, and Streffer C
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- Adolescent, Case-Control Studies, Chernobyl Nuclear Accident, Child, Combined Modality Therapy, Female, Humans, Lymphocytes pathology, Lymphocytes ultrastructure, Male, Micronuclei, Chromosome-Defective statistics & numerical data, Power Plants, Radioactive Hazard Release, Thyroid Neoplasms blood, Ukraine, Iodine Radioisotopes therapeutic use, Lymphocytes radiation effects, Neoplasms, Radiation-Induced etiology, Neoplasms, Radiation-Induced radiotherapy, Thyroid Neoplasms etiology, Thyroid Neoplasms radiotherapy
- Abstract
After the Chernobyl accident a statistically significant increase in the number of children with thyroid tumours was observed. In this study 166 children with and 75 without thyroid tumours were analysed for micronucleus formation in peripheral blood lymphocytes using the cytochalasin B approach. The following factors did not significantly affect micronucleus formation: gender, age at the time of the first (131)I treatment, tumour stage, tumour type, or metastases; a statistically significant increase in the number of micronuclei, however, was observed for the residents of Gomel compared to other locations, such as Brest, Grodno, and Minsk. The children with tumours received (131)I treatment after surgical resection of the tumours. This gave us the opportunity to systematically follow the effect of (131)I on micronucleus formation. A marked increase was observed 5 days after the (131)I treatment followed by a decrease within a 4-7 months interval up to the next application, but the pre-treatment levels were not achieved. Up to 10 therapy cycles were followed each including an analysis of micronucleus formation before and 5 days after (131)I application. The response of the children was characterised by clear individual differences and the increase/decrease pattern of micronucleus frequencies induced by iodine-131 was correlated with a decrease/increase pattern in the number of lymphocytes.
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- 2004
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17. Effects of asbestos on initiation of DNA damage, induction of DNA-strand breaks, P53-expression and apoptosis in primary, SV40-transformed and malignant human mesothelial cells.
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Burmeister B, Schwerdtle T, Poser I, Hoffmann E, Hartwig A, Müller WU, Rettenmeier AW, Seemayer NH, and Dopp E
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- Cell Line, Transformed, Comet Assay, Epithelium pathology, Fluorescent Antibody Technique, Humans, Simian virus 40 physiology, Asbestos toxicity, DNA drug effects, DNA Damage, Epithelium metabolism, Tumor Suppressor Protein p53 genetics
- Abstract
Human mesothelial cells (HMC), the progenitor cells of asbestos-induced mesothelioma, are particularly sensitive to the genotoxic effects of asbestos, although the molecular mechanisms by which asbestos induces injury in HMC are not well known. The high susceptibility of HMC to simian virus 40 (SV40)-mediated transformation is assumed to play a causative role in the pathogenesis of mesothelioma. The aim of this study was to investigate the asbestos-induced DNA damage in cultured HMC and SV40-transformed HMC (MeT-5A) compared with their malignant counterparts, i.e. human mesothelioma cells (MSTO). The time-dependent initiation of DNA-strand breaks as well as the induction of oxidative DNA base modifications were key factors for investigation. HMC, MeT-5A and MSTO cells were exposed to chrysotile and crocidolite asbestos (3 microg/cm2) during different time periods (1-72 h). DNA damage was investigated by use of the Comet assay and alkaline unwinding, the latter in combination with the Fpg protein. The P53 level was analyzed by immunofluorescence, and measurement of apoptosis was conducted by flow cytometry. We found a significant induction of DNA damage in asbestos-treated HMC already after an exposure time of 1.5 h. This effect could not be observed in treated MeT-5A and MSTO cells. Also, a time-dependent significant increase in DNA-strand breaks was observed by alkaline unwinding in asbestos-treated HMC, but not in treated MeT-5A and MSTO cells. In none of the three cell lines we could detect oxidative DNA damage recognized by the Fpg protein (e.g. 8-oxo-guanine), up to 24 h after exposure to asbestos. In contrast to what was found in HMC, P53 was over-expressed in untreated MeT-5A and MSTO. The induction of apoptosis by asbestos fibers was suppressed in MeT-5A and MSTO cells. Crocidolite fibers induced the higher genotoxic effects and chrysotile the more pronounced apoptotic effects. We conclude that asbestos induces DNA damage in HMC already after a very short exposure time in the absence of 8-oxo-guanine formation. The presence of SV40-Tag in MeT-5A and MSTO cells results in an increased expression of P53, but not in additive genotoxic effects after exposure to asbestos. The deregulation of the apoptotic pathway may lead to proliferation of genomically damaged cells and finally to the development of mesothelioma.
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- 2004
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18. Micronuclei in lymphocytes of uranium miners of the former Wismut SDAG.
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Müller WU, Kryscio A, and Streffer C
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- Alcohol Drinking blood, Alcohol Drinking genetics, Alpha Particles adverse effects, Cell Nucleus drug effects, Cell Nucleus radiation effects, Cell Nucleus ultrastructure, Centromere ultrastructure, Chromosomal Instability genetics, Cytochalasin B pharmacology, Dose-Response Relationship, Radiation, Gamma Rays adverse effects, Germany, Life Style, Lung Neoplasms blood, Lung Neoplasms genetics, Occupational Diseases blood, Occupational Diseases etiology, Occupational Diseases genetics, Pulmonary Fibrosis blood, Pulmonary Fibrosis genetics, Radionuclide Imaging adverse effects, Radionuclide Imaging statistics & numerical data, Radon, Risk Factors, Smoking blood, Smoking genetics, Time Factors, Lymphocytes ultrastructure, Micronucleus Tests methods, Mining, Occupational Exposure, Uranium
- Abstract
We studied micronucleus frequencies in former German uranium miners of the Wismut SDAG (Sowjetisch-Deutsche Aktiengesellschaft). Various other groups were analyzed for comparison (individuals with lung tumors or lung fibrosis, controls). We had shown previously that micronucleus frequencies were not different among the various groups. Differences were observed, however, when centromere-positive and -negative micronuclei were distinguished. In the analyses presented here, we looked for the effects of smoking habits, alcohol consumption, vitamin uptake, chronic diseases, allergies, doing sports, gamma-GT (gamma-glutamyltranspeptidase), lymphocyte numbers, CEA (carcinoembryonic antigen), X-ray diagnostics, computer tomographies, and scintigraphies. With the exception of more than one scintigraphy carried out during the last four months before micronucleus analysis, none of the factors mentioned above significantly affected micronucleus numbers. One result deserves specific attention: individuals with low percentages of binucleated lymphocytes after in vitro cytochalasin B exposure showed higher micronucleus frequencies than those individuals with high percentages of binucleated cells. The same result was obtained for various other populations that we monitored in the past., (Copyright 2003 S. Karger AG, Basel)
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- 2004
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19. Intra- and inter-laboratory variation in the scoring of micronuclei and nucleoplasmic bridges in binucleated human lymphocytes. Results of an international slide-scoring exercise by the HUMN project.
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Fenech M, Bonassi S, Turner J, Lando C, Ceppi M, Chang WP, Holland N, Kirsch-Volders M, Zeiger E, Bigatti MP, Bolognesi C, Cao J, De Luca G, Di Giorgio M, Ferguson LR, Fucic A, Lima OG, Hadjidekova VV, Hrelia P, Jaworska A, Joksic G, Krishnaja AP, Lee TK, Martelli A, McKay MJ, Migliore L, Mirkova E, Müller WU, Odagiri Y, Orsiere T, Scarfì MR, Silva MJ, Sofuni T, Surralles J, Trenta G, Vorobtsova I, Vral A, and Zijno A
- Subjects
- Analysis of Variance, Humans, International Cooperation, Laboratories, Lymphocytes radiation effects, Male, Poisson Distribution, Reference Standards, Cell Nucleus Structures genetics, Lymphocytes physiology, Micronucleus Tests standards, Observer Variation
- Abstract
One of the objectives of the HUman MicroNucleus (HUMN) project is to identify the methodological variables that have an important impact on micronucleus (MN) or micronucleated (MNed) cell frequencies measured in human lymphocytes using the cytokinesis-block micronucleus assay. In a previous study we had shown that the scoring criteria used were likely to be an important variable. To determine the extent of residual variation when laboratories scored cells from the same cultures using the same set of standard scoring criteria, an inter-laboratory slide-scoring exercise was performed among 34 laboratories from 21 countries with a total of 51 slide scorers involved. The results of this study show that even under these optimized conditions there is a great variation in the MN frequency or MNed cell frequency obtained by individual laboratories and scorers. All laboratories ranked correctly the MNed cell frequency in cells from cultures that were unirradiated, or exposed to 1 or 2Gy of gamma rays. The study also estimated that the intra-scorer median coefficient of variation for duplicate MNed cell frequency scores is 29% for unexposed cultures and 14 and 11% for cells exposed to 1 and 2Gy, respectively. These values can be used as a standard for quality or acceptability of data in future studies. Using a Poisson regression model it was estimated that radiation dose explained 67% of the variance, while staining method, cell sample, laboratory, and covariance explained 0.6, 0.3, 6.5, and 25.6% of the variance, respectively, leaving only 3.1% of the variance unexplained. As part of this exercise, nucleoplasmic bridges were also estimated by the laboratories; however, inexperience in the use of this biomarker of chromosome rearrangement was reflected in the much greater heterogeneity in the data and the unexplained variation estimated by the Poisson model. The results of these studies indicate clearly that even after standardizing culture and scoring conditions it will be necessary to calibrate scorers and laboratories if MN, MNed cell and nucleoplasmic bridge frequencies are to be reliably compared among laboratories and among populations.
- Published
- 2003
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20. Radiation and malformations in a murine model.
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Müller WU
- Subjects
- Animals, Female, Fetal Death etiology, Gamma Rays, Male, Mice, Pregnancy, Pregnancy, Animal, Time Factors, Abnormalities, Radiation-Induced, Spermatogenesis radiation effects, Spermatozoa radiation effects
- Abstract
Thus, the results of radiation exposure of the different stages of spermatogenesis with regard to the induction of malformations in the offspring of these exposed male mice can be summarized as follows: It is possible to induce malformations in the offspring by radiation exposure of male mice of the HLG strain. This means that direct DNA damage is responsible for the induction of the observed malformations. The highest sensitivity is observed during meiosis. The fact that direct DNA damage is involved in the induction of radiation induced malformations underlines the hypothesis mentioned above, that two processes may have a major impact on malformation induction in germ cells and preimplantation stages: 'genetic predisposition' and 'genomic instability'.
- Published
- 2003
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21. Does radiotherapy affect the outcome of the comet assay?
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Müller WU, Bauch T, Streffer C, and von Mallek D
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- Alcohol Drinking adverse effects, Humans, Neoplasms pathology, Neoplasms radiotherapy, Radiation Tolerance, Radiotherapy methods, Smoking adverse effects, Comet Assay, DNA Repair radiation effects, DNA, Neoplasm radiation effects, Lymphocytes radiation effects, Radiotherapy adverse effects
- Abstract
This study was designed to assess possible effects of fractionated radiotherapy (5 or 10 fractions at 2 Gy per fraction) on the DNA repair capacity of lymphocytes, as measured by the comet assay. 50 patients with various tumour types were chosen. They had received no chemotherapy during the 6 months prior to radiotherapy and did not receive cortisone. 10 ml of heparinized blood was collected before radiotherapy, after 5 fractions and after 10 fractions. Lymphocytes were isolated and analysed using the comet assay. On average, no effect on DNA repair capacity was observed that could be attributed to radiotherapy. On an individual basis, there were a few patients who showed a comparatively pronounced variability in their response to radiotherapy (three patients with a relative coefficient of variability of more than 30%). There was some indication of a weak correlation between poor repair capacity and severe side effects in normal tissue. We also found that alcohol in particular, and smoking to some extent, may impair repair capacity during radiotherapy. Age, gender, field size, medication and tumour entity showed no effect on repair capacity.
- Published
- 2002
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22. The micronucleus assay in human lymphocytes after high radiation doses (5-15 Gy).
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Müller WU and Rode A
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- Cytochalasin D administration & dosage, Dose-Response Relationship, Drug, Humans, Lymphocytes ultrastructure, Lymphocytes radiation effects, Micronucleus Tests
- Abstract
Individuals can be exposed to high doses (more than 5Gy) during radiation accidents. It is, of course, helpful to the physician to have biological indicators also for such high doses. The problem with most cytogenetic indicators is, that the response levels off at doses starting around 5-7Gy of low LET radiation and that the dose-response curve even declines after doses exceeding about 10Gy. Thus, it may be difficult to decide, whether the dose was, for example, 8 or 14Gy. We studied how the micronucleus assay can be used to give information also in the high dose range. It turned out that micronucleus frequency itself cannot be used for the estimation of doses exceeding about 5-7Gy. There are, however, at least three other endpoints that can be determined in the cytochalasin B assay that can assist the decision in the high dose range: (1) the number of mononucleated cells; (2) the ratio of tri- to tetranucleated cells; (3) the average micronucleus frequency in micronucleus positive binucleated cells.
- Published
- 2002
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23. A cytogenetic analysis of the long-term effect of uranium mining on peripheral lymphocytes using the micronucleus-centromere assay.
- Author
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Kryscio A, Ulrich Müller WU, Wojcik A, Kotschy N, Grobelny S, and Streffer C
- Subjects
- Adult, Aged, Case-Control Studies, Centromere genetics, Centromere radiation effects, Cytogenetic Analysis, Female, Humans, Lung Neoplasms genetics, Lymphocytes drug effects, Male, Middle Aged, Mining, Lymphocytes radiation effects, Micronucleus Tests, Occupational Exposure, Uranium toxicity
- Abstract
Purpose: To assess the long-term effect of radiation exposure of uranium miners on a cytogenetic endpoint: micronuclei (Mn) with and without a centromere., Materials and Methods: Mn were scored using the cytochalasin-B technique. It is known that Mn can comprise acentric fragments or/and whole chromosomes. Mn containing whole chromosomes were identified by means of fluorescence in situ hybridization (FISH) with a centromere-specific probe. The frequency and percentage of Mn were analysed with centromeres (MnC+) in lymphocytes of healthy donors and uranium miners with large radiation exposures several decades ago employed by the Wismut AG in the former German Democratic Republic. The miners were subdivided into those with and those without bronchial carcinoma., Results: It was shown previously that the relative frequency of MnC+ decreased with dose; this means that the number of Mn originating from acentric fragments increases. In the study presented here, no statistically significant difference in the overall Mn frequency was seen between the analysed groups. The fraction of MnC+, however, was highest in lymphocytes of healthy male donors (mean: 74.6%) followed by healthy miners (mean: 62.1%) and those suffering from cancer (mean: 55.8%)., Conclusion: The results indicate the occurrence of a genomic instability in lymphocytes of miners, especially those with cancer. It appears that the low percentage of MnC+ may be a marker of genomic instability and cancer predisposition.
- Published
- 2001
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24. Radiation sensitivity of lymphocytes from healthy individuals and cancer patients as measured by the comet assay.
- Author
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Müller WU, Bauch T, Stüben G, Sack H, and Streffer C
- Subjects
- Comet Assay, Dose-Response Relationship, Radiation, Female, Humans, In Vitro Techniques, Kinetics, Male, Middle Aged, Neoplasms immunology, Reference Values, X-Rays, DNA Damage, DNA Repair, Lymphocytes radiation effects, Neoplasms blood, Neoplasms radiotherapy
- Abstract
Lymphocytes of healthy volunteers (n = 24) and of tumour patients (n = 30, 18 of whom had experienced severe side-effects) were irradiated with x-rays in vitro. DNA damage was analysed after 0.25-2 Gy and DNA repair after 2 Gy, and quantification of both endpoints was done by the comet assay. The individual differences in radiation-induced DNA damage as well as in the repair kinetics were observed to be striking for both healthy donors and tumour patients. After a repair time of 3 h, following 2 Gy x-irradiation, some of the healthy volunteers showed no residual DNA damage at all in their lymphocytes, whereas others revealed about 30%. There was no indication that our results were affected by either age, gender or smoking habits. Slow repair kinetics and high amounts of residual damage were characteristic for many but not all tumour patients who had experienced severe side-effects in their normal tissues during or after radiotherapy (n = 18). Our conclusion is that those individuals showing poor DNA repair characteristics in the lymphocytes following in vitro irradiation, have a high probability of being radiosensitive. The opposite conclusion is not necessarily true: if repair is effective, this does not mean that the individual is radioresistant, because factors other than impaired repair may cause radiosensitivity.
- Published
- 2001
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25. HUman MicroNucleus project: international database comparison for results with the cytokinesis-block micronucleus assay in human lymphocytes: I. Effect of laboratory protocol, scoring criteria, and host factors on the frequency of micronuclei.
- Author
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Bonassi S, Fenech M, Lando C, Lin YP, Ceppi M, Chang WP, Holland N, Kirsch-Volders M, Zeiger E, Ban S, Barale R, Bigatti MP, Bolognesi C, Jia C, Di Giorgio M, Ferguson LR, Fucic A, Lima OG, Hrelia P, Krishnaja AP, Lee TK, Migliore L, Mikhalevich L, Mirkova E, Mosesso P, Müller WU, Odagiri Y, Scarffi MR, Szabova E, Vorobtsova I, Vral A, and Zijno A
- Subjects
- Adolescent, Adult, Age Distribution, Age Factors, Artifacts, Cell Division genetics, Child, Data Interpretation, Statistical, Female, Genetic Predisposition to Disease, Humans, Male, Mass Screening statistics & numerical data, Micronucleus Tests methods, Micronucleus Tests statistics & numerical data, Middle Aged, Reproducibility of Results, Research Design standards, Sex Distribution, Sex Factors, Surveys and Questionnaires, Databases, Factual statistics & numerical data, Lymphocytes pathology, Mass Screening standards, Micronucleus Tests standards
- Abstract
Micronucleus (MN) expression in peripheral blood lymphocytes is well established as a standard method for monitoring chromosome damage in human populations. The first results of an analysis of pooled data from laboratories using the cytokinesis-block micronucleus (CBMN) assay and participating in the HUMN (HUman MicroNucleus project) international collaborative study are presented. The effects of laboratory protocol, scoring criteria, and host factors on baseline micronucleated binucleate cell (MNC) frequency are evaluated, and a reference range of "normal" values against which future studies may be compared is provided. Primary data from historical records were submitted by 25 laboratories distributed in 16 countries. This resulted in a database of nearly 7000 subjects. Potentially significant differences were present in the methods used by participating laboratories, such as in the type of culture medium, the concentration of cytochalasin-B, the percentage of fetal calf serum, and in the culture method. Differences in criteria for scoring micronuclei were also evident. The overall median MNC frequency in nonexposed (i.e., normal) subjects was 6.5 per thousand and the interquartile range was between 3 and 12 per thousand. An increase in MNC frequency with age was evident in all but two laboratories. The effect of gender, although not so evident in all databases, was also present, with females having a 19% higher level of MNC frequency (95% confidence interval: 14-24%). Statistical analyses were performed using random-effects models for correlated data. Our best model, which included exposure to genotoxic factors, host factors, methods, and scoring criteria, explained 75% of the total variance, with the largest contribution attributable to laboratory methods., (Copyright 2001 Wiley-Liss, Inc.)
- Published
- 2001
26. Biomarkers of genetic damage and inflammation in blood and bronchoalveolar lavage fluid among former German uranium miners: a pilot study.
- Author
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Popp W, Plappert U, Müller WU, Rehn B, Schneider J, Braun A, Bauer PC, Vahrenholz C, Presek P, Brauksiepe A, Enderle G, Wüst T, Bruch J, Fliedner TM, Konietzko N, Streffer C, Woitowitz HJ, and Norpoth K
- Subjects
- Aged, Blood radiation effects, Bronchoalveolar Lavage Fluid chemistry, Chromosome Aberrations, Cohort Studies, Comet Assay, Fibronectins biosynthesis, Germany, Humans, Lung Neoplasms blood, Lung Neoplasms etiology, Lung Neoplasms metabolism, Lymphocytes radiation effects, Male, Micronuclei, Chromosome-Defective radiation effects, Middle Aged, Neoplasms, Radiation-Induced blood, Neoplasms, Radiation-Induced metabolism, Phospholipids biosynthesis, Pilot Projects, Risk Factors, Smoking, Tumor Necrosis Factor-alpha biosynthesis, Tumor Suppressor Protein p53 biosynthesis, Uranium, Biomarkers, Mining, Occupational Exposure
- Abstract
Former East German uranium miners who are known to have been exposed to radon are estimated to be at high risk for lung carcinogenesis. Among these miners over 200 occupationally caused lung cancer cases are expected to occur each year, resulting in a total of 7,000-24,000 excess lung cancer cases in the coming years. It is still unknown whether there is a correlation between biomarkers and the exposure of the uranium miners to ionizing radiation that might enable us to trace those miners with high lung cancer risk. The primary aim of this pilot study was to test the possibility of performing a biomarker study in this unique cohort of former uranium miners in spite of several limitations that had to be taken into consideration when comparing them with healthy controls, such as old age, age-dependent diseases and potential confounding artefacts from dissimilar smoking patterns. The second aim was to test a range of biomarkers for DNA damage and inflammation in leukocytes and bronchoalveolar fluid for their ability to detect biological effects. In this cohort of miners we found an increased frequency of chromosomal aberrations in blood lymphocytes and an increased prevalence of both fibronectin and tumour necrosis factor alpha in the bronchoalveolar fluid.
- Published
- 2000
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27. DNA excision repair and DNA damage-induced apoptosis are linked to Poly(ADP-ribosyl)ation but have different requirements for p53.
- Author
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Beneke R, Geisen C, Zevnik B, Bauch T, Müller WU, Küpper JH, and Möröy T
- Subjects
- Animals, Cell Line, DNA Damage, Female, Humans, Male, Mice, Mice, Inbred C3H, Mice, Inbred C57BL, Mice, Transgenic, Poly Adenosine Diphosphate Ribose metabolism, Poly(ADP-ribose) Polymerases genetics, Poly(ADP-ribose) Polymerases metabolism, Thymus Gland cytology, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 physiology, Apoptosis drug effects, Apoptosis radiation effects, DNA Repair, Poly(ADP-ribose) Polymerases physiology, Tumor Suppressor Protein p53 metabolism
- Abstract
Poly(ADP-ribose) polymerase (PARP) is a DNA binding zinc finger protein that catalyzes the transfer of ADP-ribose residues from NAD(+) to itself and different chromatin constituents, forming branched ADP-ribose polymers. The enzymatic activity of PARP is induced upon DNA damage and the PARP protein is cleaved during apoptosis, which suggested a role of PARP in DNA repair and DNA damage-induced cell death. We have generated transgenic mice that lack PARP activity in thymocytes owing to the targeted expression of a dominant negative form of PARP. In the presence of single-strand DNA breaks, the absence of PARP activity correlated with a strongly increased rate of apoptosis compared to cells with intact PARP activity. We found that blockage of PARP activity leads to a drastic increase of p53 expression and activity after DNA damage and correlates with an accelerated onset of Bax expression. DNA repair is almost completely blocked in PARP-deficient thymocytes regardless of p53 status. We found the same increased susceptibility to apoptosis in PARP null mice, a similar inhibition of DNA repair kinetics, and the same upregulation of p53 in response to DNA damage. Thus, based on two different experimental in vivo models, we identify a direct, p53-independent, functional connection between poly(ADP-ribosyl)ation and the DNA excision repair machinery. Furthermore, we propose a p53-dependent link between PARP activity and DNA damage-induced cell death.
- Published
- 2000
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28. Chromosomal aberrations induced in mice bone marrow by treating with cisplatin and irradiation.
- Author
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Würschmidt F, Bardenheuer MJ, Müller WU, and Molls M
- Subjects
- Animals, Bone Marrow Cells cytology, Cell Division, Cobalt Radioisotopes, Dose-Response Relationship, Drug, Dose-Response Relationship, Radiation, Female, Mice, Mice, Inbred Strains, Mice, Nude, Bone Marrow Cells drug effects, Bone Marrow Cells radiation effects, Chromosome Aberrations, Cisplatin toxicity
- Abstract
Background: The aim of this study was to quantify the combined effect of cisplatin and radiation on chromosomal damage with emphasis on the time interval between cisplatin and radiation., Methods and Materials: Bone marrow of female NMRI-nu(+) mice was taken as a model system for a highly proliferative tissue irradiated with cobalt-60 (1 to 4 Gy). Cisplatin was injected intraperitoneally (i.p.) at 1.1 to 36 mg/kg. Cisplatin was given at various time intervals before and after radiation. Bone marrow and metaphases were prepared according to standard procedures., Results: The percentage of aberrant metaphases after radiation or cisplatin alone increased in a dose-dependent manner (sigmoidal dose-response curve). Combining both modalities led to additive values at all time points for the percentage of aberrant metaphases. Borderline significant (p < 0.05) supraadditive effects were found 2 hours before or 1 hour after irradiation. However, a supraadditive percentage of aberrant chromosomes was found only at 2 or 1.5 hours with cisplatin before irradiation indicating the dependence of supraadditivity on the chosen parameter., Conclusion: It is doubtful to expect a true supraadditive or "radiosensitizing" effect, e.g. in the clinical setting from combined treatment with cisplatin and radiation. Rather, cisplatin might act as an independent cytotoxic agent.
- Published
- 2000
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29. Lethal and teratogenic effects in two successive generations of the HLG mouse strain after radiation exposure of zygotes -- association with genomic instability?
- Author
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Pils S, Müller WU, and Streffer C
- Subjects
- Animals, Congenital Abnormalities genetics, Congenital Abnormalities mortality, Embryo Implantation radiation effects, Embryo Loss etiology, Embryonic Development radiation effects, Female, Fertility radiation effects, Fetal Death etiology, Genome, Infertility etiology, Male, Mice, Mutation radiation effects, Pregnancy, X-Rays adverse effects, Zygote growth & development, Congenital Abnormalities etiology, Zygote radiation effects
- Abstract
We analysed the transmission of lethal and teratogenic events to the subsequent generation in HLG/Zte mice after exposure of the zygote stage to 1 Gy X-rays. As observed in previous studies, our results on teratogenic events occurring in the same generation, which was exposed during the zygote stage, reveal a significantly higher risk for the induction of gastroschisis. Interesting new insights came from the study of lethal and teratogenic effects in the generation obtained after mating female mice, which were exposed during their zygote stage, to unexposed males. An approximately 2-fold higher level of damage was manifest in this generation compared with controls, expressed mainly as a significant increase of prenatal mortality (P<0.01). Although there was an increase in the number of malformed fetuses on day 19 of gestation (6.5% cases of gastroschisis compared to 3.5% in the controls), the frequency of gastroschisis in the exposed group was just not statistically significant (P>0.05). These results are in line with the hypothesis that genomic instability is involved in the damage seen after radiation exposure of the zygote stage of HLG mice., (Copyright 1999 Elsevier Science B.V.)
- Published
- 1999
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30. Optimization and standardization of the "comet assay" for analyzing the repair of DNA damage in cells.
- Author
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Bauch T, Böcker W, Mallek U, Müller WU, and Streffer C
- Subjects
- Adult, Cell Survival radiation effects, Dose-Response Relationship, Radiation, Female, Humans, Male, Middle Aged, Sensitivity and Specificity, DNA Damage radiation effects, DNA Repair radiation effects, Electrophoresis, Agar Gel methods, Tumor Cells, Cultured radiation effects
- Abstract
Background: The "comet assay" has become an interesting and a very useful tool for the analysis of the induction and amount of DNA damage in single cells thus offering the opportunity to measure the effectiveness of DNA repair. On the basis of the Ostling and Johanson protocol we have developed a modified method with increased sensitivity and high reproducibility., Material and Methods: Human tumor cells or isolated human peripheral blood lymphocytes were analyzed in the experiments. The amount of DNA damage and the effectiveness of DNA repair was measured after X-irradiation using the "comet assay" technique., Results: In this presentation the influences of different methodological factors like agarose concentration, buffer pH, electrophoresis time, electric field strength on the applicability of the "comet assay" are described in detail and optimum conditions for "comet assay" experiments have been evaluated. Additionally the authors will show a comparison of different fluorescent DNA dyes pointing out their advantages or disadvantages for "comet" analysis. The usefulness of this technique and its capabilities are exemplified by showing DNA repair kinetics of human lymphocytes of different healthy or radiosensitive donors after in-vitro irradiation with 2 Gy X-rays., Conclusions: This paper presents data on the optimization and standardization of the original "comet assay" leading to an extremely fast and practicable protocol in the field of single cell gel electrophoresis. After irradiation with 0.1 Gy an increase in the amount of DNA damage can be measured with high statistical significance and the DNA repair capacity of individual cells after X-ray doses of 2 Gy can be analyzed with high reproducibility. The results comparing DNA repair capacities of different donors point out that the "comet assay" may have the potential for the estimation of individual radiosensitivity.
- Published
- 1999
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31. Radiation-induced malformations after exposure of murine germ cells in various stages of spermatogenesis.
- Author
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Müller WU, Streffer C, Wojcik A, and Niedereichholz F
- Subjects
- Animals, Embryonic Development radiation effects, Female, Gamma Rays, Male, Meiosis radiation effects, Mice, Paternal Exposure, Pregnancy, Congenital Abnormalities etiology, Spermatogenesis radiation effects, Spermatozoa radiation effects
- Abstract
We studied radiation effects in day 19 fetuses of the mouse strain 'Heiligenberger' after exposure (2.8 Gy, 137 Cs gamma rays, dose rate 0.28 Gy/h) of their fathers. We observed an increased lethality (exclusively due to preimplantation death and early resorptions) after exposure of all stages of spermatogenesis with the exception of early spermatogonia. In addition, there was a significant increase in the frequency of malformed fetuses (gastroschises only); this increase was observed primarily after exposure of the meiotic stages., (Copyright 1999 Elsevier Science B.V.)
- Published
- 1999
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32. Automated comet assay analysis.
- Author
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Böcker W, Rolf W, Bauch T, Müller WU, and Streffer C
- Subjects
- Algorithms, Automation methods, Electrophoresis, Humans, Image Processing, Computer-Assisted, Kinetics, Lymphocytes cytology, Sensitivity and Specificity, Comet Assay methods, DNA Damage
- Abstract
Background: Recently the "comet assay" or "single-cell gel electrophoresis assay" has been established as a sensitive method for the detection of DNA damage and repair. Most of the software now available to quantify various parameters for DNA damage requires the interaction of a human observer. In this report, we describe an automated analysis system that is based on self-developed software and hardware and needs minimal human interaction., Methods: The image analysis is divided into two parts: 1) automatic cell recognition and comet classification and 2) quantification of desired comet parameters. Image preprocessing, segmentation, and feature classification were developed with algorithms based on mathematical morphology. To enhance evaluation speed, we have introduced parallel processing of data under the Windows NT operating system (Microsoft Corporation, Redmond, WA). Use of an analogue real-time autofocus unit (Böcker et al.: Phys Med Biol 1997;42:1981-1992) allows for faster analysis., Results: Our recognition software shows a sensitivity of 95.2% and a specificity of 92.7% when tested on test samples from routine work with DNA damage by low-dose radiation (0-2 Gy). The parallel hardware and software concept enables us to analyze 100 comets on one slide in less than 15 min., Conclusions: A comparison of measurements made on the same samples by manual and automated analysis systems revealed that there are no significant differences. The slope of the dose-response curves and the repair kinetics are very similar and demonstrate that automatic comet assay analysis is possible.
- Published
- 1999
33. Micronuclei-biological indicator for retrospective dosimetry after exposure to ionizing radiation.
- Author
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Streffer C, Müller WU, Kryscio A, and Böcker W
- Subjects
- Cell Division radiation effects, Cell Nucleus radiation effects, Coloring Agents metabolism, Cytochalasin B pharmacology, DNA Probes genetics, Dose-Response Relationship, Radiation, Humans, Image Processing, Computer-Assisted, In Situ Hybridization, Fluorescence, Lymphocytes radiation effects, Micronucleus Tests, Neutrons, Occupational Exposure, Radioactive Hazard Release, Sensitivity and Specificity, X-Rays, Micronuclei, Chromosome-Defective metabolism, Radiation, Ionizing, Radiometry
- Abstract
Micronuclei can be measured through a conventional method after staining with Giemsa or fluorescence dyes for DNA. However, a technique with cell proliferation control should be preferred. This is done by incubation with cytochalasin B and counting the micronuclei in binucleated cells. Satisfactory dose relationships are observed after irradiation of human lymphocytes in vitro. The RBE for fast neutrons is around three. An automatic analysis is possible by image analysis. The dose range in which significant increases can be observed is 0.3 to 5 Gy X-rays. The assay becomes more sensitive when the micronuclei are determined only in B-lymphocytes. Another possibility exists by determination of the number of micronuclei with centromeres. For this purpose the hybridization with pancentromeric DNA probes and fluorescence labelling is of advantage. By this technique a radiation dose of 0.1 Gy X-rays can be detected. It is apparently also possible under these conditions to detect radiation exposures which have taken place decades before the measurements., (Copyright 1998 Elsevier Science B.V.)
- Published
- 1998
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34. The sensitivity of the in vitro cytokinesis-blocked micronucleus assay in lymphocytes for different and combined radiation qualities.
- Author
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Wuttke K, Müller WU, and Streffer C
- Subjects
- Adult, Cell Division, Confidence Intervals, Dose-Response Relationship, Radiation, Female, Humans, In Vitro Techniques, Male, Neutrons, Poisson Distribution, Sensitivity and Specificity, X-Rays, Lymphocytes radiation effects, Micronucleus Tests methods
- Abstract
Purpose: The dose-response relationship and the relative biological effectiveness (RBE) for the induction of micronuclei in lymphocytes was analyzed after irradiation in vitro with a 6-MeV neutron beam that was followed by 240-kV X-rays. The dose range of the combined exposure comprised 1 to 3 Gy. For reference, the dose-effect relationships found after X-ray (0.5 to 5 Gy)- and neutron (0.5 to 4 Gy) exposure applied separately are presented. The possibility of an interaction between the 2 radiation qualities is investigated by the method of isobole calculation termed "envelope of additivity"., Methods: Micronuclei were analyzed in PHA-stimulated, cytokinesis-blocked human lymphocytes., Results: The dose-response relationships for the micronucleus frequencies induced by the neutron irradiation, as well as by the mixed exposure, were linear. A saturation effect was indicated after neutron doses higher than 3 Gy. After low LET exposure the dose-response curves were describable by a linear-quadratic model. For neutron-induced micronucleus frequencies, RBE-values of 2 to 3 and for the combined exposure RBE values of 1.5 to 2 were calculated for a range of effect of 0.5 to 1.5 micronuclei/binucleated lymphocyte. No indication was found for an interaction between the damage induced by X-rays and that produced by neutrons under our experimental conditions., Conclusions: These studies demonstrate a clear dependence of micronucleus induction on radiation quality and emphasize the usefulness of the micronucleus assay in biological dosimetry, also in cases in which high LET radiation or a mixed beam is involved as the radiation source.
- Published
- 1998
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35. Image analysis of comet assay measurements.
- Author
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Böcker W, Bauch T, Müller WU, and Streffer C
- Subjects
- Ataxia Telangiectasia pathology, Fibroblasts ultrastructure, Fluorescence, Humans, Lymphocytes ultrastructure, Mathematical Computing, Microscopy, Confocal, Reproducibility of Results, Software, DNA analysis, DNA Damage, Electrophoresis methods, Image Processing, Computer-Assisted methods
- Abstract
In the last decade the 'comet assay' or 'single cell gel electrophoresis assay' has been established as a sensitive method for the detection of DNA damage and the measurement of its recovery. The results published in the literature have often been obtained with different methods for comet structure measurement. In most cases these data are not comparable with each other. Even when using similar systems for the analysis, it is difficult to obtain matching data. This presentation will describe some technical aspects of our measurement equipment and evaluation software. It focuses on necessary experimental conditions to minimize errors in obtaining such data. The software developed here allows the rapid analysis of the microscopic samples (< 2 s per image). The image analysis was designed with respect to the morphological shapes of comet cells, which were investigated with a confocal laser microscope. The system is built with standard components which are commercially available. As a measure of the amount of DNA damage the ratio of fluorescence intensity was used inside the comet tail and the fluorescence intensity of the comet head. Other parameters such as DNA content, comet area, head radius, tail length and tail moment are also determined. The reproducibility of the system has been evaluated in several experiments over a period of 5 years.
- Published
- 1997
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36. A fast autofocus unit for fluorescence microscopy.
- Author
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Böcker W, Rolf W, Müller WU, and Streffer C
- Subjects
- Algorithms, Automation, Equipment Design, Fibroblasts cytology, Humans, Lymphocytes cytology, Microscopy, Fluorescence methods, Neoplasms pathology, Reproducibility of Results, Microscopy, Fluorescence instrumentation
- Abstract
In this paper a fast autofocus unit is introduced for fluorescence microscopy based on image content information. The module, an electronic board with several differentiators and integrators, is designed for high-speed autofocusing and is directly coupled to the output of the video camera. A Leitz MPV II fluorescence microscope with x, y, z stepping motors was used as basic equipment. The microscope images were focused by using an intensified target camera with a following analogue-digital converter and a PC. Thus one obtains a focus value for the current image within one video cycle. Furthermore, it is possible to process three different focus functions (weighted intensity, first derivative and second derivative) simultaneously. The flexibility to select a certain focus function or a combination of these functions allows the use of the analogue detector for various cell types and fluorescent dyes. In order to test the experimental set-up we use three different kinds of biological specimen (lymphocytes, fibroblasts and comet cells) which are distinguished by large differences in their morphological structure. Successful focusing is carried out in more than 95% of cases (investigation of several hundred different cells). The focusing procedure is almost finished after 1-2 s.
- Published
- 1997
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37. Detection of chromosome 2 and chromosome 7 within X-ray- or colchicine-induced micronuclei by fluorescence in situ hybridization.
- Author
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Wuttke K, Streffer C, and Müller WU
- Subjects
- Aneuploidy, Cell Nucleus drug effects, Cell Nucleus genetics, Chromosome Banding methods, Chromosomes, Human, Pair 2 drug effects, Chromosomes, Human, Pair 2 radiation effects, Chromosomes, Human, Pair 7 drug effects, Chromosomes, Human, Pair 7 radiation effects, Female, Humans, Lymphocytes drug effects, Lymphocytes radiation effects, Micronucleus Tests, Spindle Apparatus drug effects, X-Rays, Cell Nucleus radiation effects, Chromosomes, Human, Pair 2 genetics, Chromosomes, Human, Pair 7 genetics, Colchicine toxicity, In Situ Hybridization, Fluorescence methods
- Abstract
The occurrence of chromosome 2 and chromosome 7 within micronuclei of binucleated lymphocytes induced by X-rays or colchicine was scored using the whole chromosome painting technique. The observed frequency of involvement in micronucleus formation was compared with the yield that would be expected theoretically, when the random participation of each chromosome is assumed. No difference was observed between the expected and observed inclusion of chromosome 2 or chromosome 7 into micronuclei after X-ray exposure (2.5 Gy). This was also the case for chromosome 2, but not for chromosome 7 after colchicine treatment (0.04/0.06 microgram/ml); chromosome 7 was detected approximately 1.5 times more frequently in micronucleus formation than would be expected from the assumption of a random distribution.
- Published
- 1997
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38. Genetic analysis of the cause of gastroschisis in the HLG mouse strain.
- Author
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Hillebrandt S, Streffer C, and Müller WU
- Subjects
- Abdominal Muscles embryology, Abnormalities, Radiation-Induced mortality, Animals, Crosses, Genetic, Female, Fetal Death genetics, Hernia embryology, Hernia genetics, Homozygote, Male, Mice, Mice, Inbred C57BL, Mice, Inbred Strains, Models, Genetic, Mutation, Pregnancy, X-Rays, Abdominal Muscles abnormalities, Abdominal Muscles radiation effects, Abnormalities, Radiation-Induced genetics, Fetus radiation effects
- Abstract
An inbred mouse strain HLG shows a high incidence of gastroschisis after X-ray exposure to the zygotes. About 11% of the fetuses display this malformation after irradiation with 1 Gy. The C57BL-strain does not show the increased frequency of gastroschisis after radiation-exposure to the zygotes. The genetic background of this malformation was investigated in a backcross of HLG x C57BL females to HLG males. The pregnant HLG x C57BL females were irradiated in a stage in which the (HLG x C57BL) x HLG [BC1] embryos were in the 1-cell stage. The frequency of gastroschisis in the BC1 generation was compared with a genetic model of a single recessive mutation with 11% penetrance. This frequency does not fit a single-locus inheritance. The number of loci involved was estimated to be about two or three. HLG mouse strain may be a valuable animal model in the study of polygenic traits.
- Published
- 1996
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39. Effects of cell cycle specific exposure to 3H-thymidine or 3H-arginine on development and cell proliferation of mouse embryos.
- Author
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Müller WU, Heckeley N, and Streffer C
- Subjects
- Animals, Cell Cycle, Cell Division drug effects, Female, Male, Mice, Arginine metabolism, Embryonic and Fetal Development radiation effects, Thymidine metabolism, Tritium toxicity
- Abstract
One-cell mouse embryos were exposed to either 3H-thymidine (100 or 200 kBq/ml) or 3H-arginine (2.5 to 50 kBq/ml) for 2 h either in G1, S or G2 phase. 3H-Arginine affected embryonic development and cell proliferation in an activity-dependent way irrespective of the cell cycle stage exposed, whereas 3H-thymidine was effective only at higher activities and only after exposure during S phase.
- Published
- 1996
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40. Micronuclei: a biological indicator of radiation damage.
- Author
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Müller WU, Nüsse M, Miller BM, Slavotinek A, Viaggi S, and Streffer C
- Subjects
- Animals, Chromosomes metabolism, Chromosomes radiation effects, DNA metabolism, DNA radiation effects, Dose-Response Relationship, Radiation, Flow Cytometry, Humans, In Vitro Techniques, Lymphocytes metabolism, Lymphocytes radiation effects, Lymphocytes ultrastructure, Micronuclei, Chromosome-Defective metabolism, Micronuclei, Chromosome-Defective radiation effects
- Published
- 1996
- Full Text
- View/download PDF
41. Automated scoring of micronuclei in binucleated human lymphocytes.
- Author
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Böcker W, Streffer C, Müller WU, and Yu C
- Subjects
- Automation, Dose-Response Relationship, Radiation, Humans, Image Processing, Computer-Assisted, Reproducibility of Results, X-Rays, Lymphocytes radiation effects, Micronuclei, Chromosome-Defective radiation effects, Micronucleus Tests methods
- Abstract
Manual and automatic scoring of micronuclei (MN) in binucleated human lymphocytes (BNC) were compared after irradiation of whole blood samples. The blood samples were irradiated with X-ray doses (1, 2 or 3 Gy) and stained with Giemsa. The preparation technique was optimized in such a way that acceptable conditions (cell density, contrast) were obtained for both scoring procedures. To estimate the quality of automatic micronucleus detection, two researchers who had different experience in scoring MN (6 months and 5 years) analysed the samples independently from each other. Automatic scoring was carried out with a digital image analysis system and the recognition procedure was divided into two parts. The BNC positions were detected with low microscope magnification (100x), and the recognition of micronuclei within the cytoplasm of the classified BNC was carried out at high magnification (630x). A fuzzy logic classification system as well as two different segmentation steps (preclassification and postclassification) made it possible that about 94% of all automatically recognized BNC were classified correctly). On the other hand, the classification system was optimized in such a way that false positive decisions were minimized (95% of automatically recognized micronuclei were classified correctly). Failure to recognize micronuclei (8.5%-25% false negatives) was mainly due to extremely small micronuclei, poor contrast with respect to the cytoplasm, and aggregation of micronuclei especially at higher doses.
- Published
- 1996
- Full Text
- View/download PDF
42. Analysis of DNA damage recovery processes in the adaptive response to ionizing radiation in human lymphocytes.
- Author
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Wojcik A, Sauer C, Zölzer F, Bauch T, and Müller WU
- Subjects
- Adult, Cell Division radiation effects, Cells, Cultured radiation effects, Chromosome Aberrations, Dose-Response Relationship, Radiation, Electrophoresis, Agar Gel, Female, Genetic Techniques, Humans, Male, Adaptation, Physiological, DNA Damage, DNA Repair, Lymphocytes cytology, Lymphocytes radiation effects
- Abstract
It has been frequently suggested that the adaptive response to ionizing radiation involves the induction of a chromosomal repair mechanism. Although several lines of evidence favour this assumption, direct proof is lacking. We have chosen to study this question with the help of the comet assay. Lymphocytes from three human donors were given an adapting dose of 0.05 Gy 16 h after mitogenic stimulation and a challenging dose of 2 Gy 5 h thereafter. While a portion of the cells was removed from the cultures for the comet assay, remaining cells were harvested at 52 h culture time and screened for chromosomal aberrations. In some experiments an analysis of cell proliferation was additionally carried out by flow cytometry. In the comet assay a reduced level of initial damage and an increased repair capacity was observed in the adapted + challenged cells; however, this did not result in a reduction of the aberration frequencies. No effect of the adapting dose on cell proliferation was detectable. The analysis of comet distributions revealed that the observed enhanced repair capacity was due to the presence of a subpopulation of slowly repairing cells in the challenged lymphocytes and the lack of such a subpopulation in the adapted + challenged cells. We assume that the slowly repairing cells were quiescent G0 lymphocytes which were removed from the adapted + challenged cell population, probably by apoptotic-like processes.
- Published
- 1996
- Full Text
- View/download PDF
43. Automated cell cycle analysis with fluorescence microscopy and image analysis.
- Author
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Böcker W, Gantenberg HW, Müller WU, and Streffer C
- Subjects
- Algorithms, Biophysical Phenomena, Biophysics, DNA analysis, Humans, Leukocytes chemistry, Leukocytes cytology, Reproducibility of Results, Signal Processing, Computer-Assisted, Software, Cell Cycle, Image Processing, Computer-Assisted methods, Microscopy, Fluorescence methods
- Abstract
Automatic cell cycle analysis (DNA histograms) is usually performed with flow cytometry. In cases when only few cells are available, the DNA content has to be measured with a fluorescence microscope combined with sensitive camera systems (SIT, MCP, cooled CCDs) and a frame grabber for image analysis. The fluorescent cells are observed on the monitor of the image analyser. The DNA content of specific cells of interest is calculated after an interactive selection via mouse click on the monitor screen. It is desirable to automate this time-consuming procedure by a computer "cell-finding' and "cell-measurement' system, which is comparable in speed and measurement accuracy with manual scoring. A software program, based on image analysis, was designed for the automated cell finding, the cell measurement, and finally the interactive DNA data evaluation. The system has already been used to determine cell cycle stages in which specific manipulations of a lymphocyte culture were required. However, the system is also able to determine, automatically, DNA distributions of different kinds of cell (different leucocytes) within one sample, as long as the automatic recognition software can distinguish between them by morphological differences.
- Published
- 1996
- Full Text
- View/download PDF
44. Do DNA double-strand breaks induced by Alu I lead to development of novel aberrations in the second and third post-treatment mitoses?
- Author
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Wojcik A, Bonk K, Müller WU, Obe G, and Streffer C
- Subjects
- Animals, Cell Membrane Permeability drug effects, Cell Nucleus drug effects, Cleavage Stage, Ovum, Cytoplasm, Female, Male, Mice, Microinjections, Chromosome Aberrations, DNA Damage, Deoxyribonucleases, Type II Site-Specific administration & dosage, Mitosis, Streptolysins administration & dosage
- Abstract
Several authors have reported that ionizing radiation can give rise to novel aberrations several mitotic divisions after the exposure. At our institute this phenomenon has been observed in mouse preimplantation embryos. This cell system is uniquely well suited for such investigations because the first three cell divisions show a high degree of synchrony. Thus the expression of chromosomal aberrations at the first, second and third mitosis after irradiation can be scored unambiguously. To investigate whether DNA double-strand breaks may be the lesions responsible for the delayed expression of chromosomal aberrations, we have studied the frequencies of aberrations in the first, second and third mitosis after treatment of one-cell mouse embryos with the restriction enzyme Alu I. Embryos were permeabilized with Streptolysin-O. The results indicate that the induction of double-strand breaks does not lead to novel aberrations in the third post-treatment mitosis. Several embryos scored at the second mitosis showed very high numbers of aberrations, indicating that Alu I may remain active in the cells for a period of one cell cycle. After treatment with Streptolysin-O alone, enhanced aberration frequencies were observed in the third post-treatment mitosis, suggesting that membrane damage has a delayed effect on the cellular integrity.
- Published
- 1996
45. Micronuclei in lymphocytes of children from the vicinity of Chernobyl before and after 131I therapy for thyroid cancer.
- Author
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Wuttke K, Streffer C, Müller WU, Reiners C, Biko J, and Demidchik E
- Subjects
- Adolescent, Child, Chromosome Aberrations, Female, Humans, Iodine Radioisotopes therapeutic use, Lymphocytes pathology, Male, Micronuclei, Chromosome-Defective ultrastructure, Power Plants, Radioactive Hazard Release, Time Factors, Ukraine, DNA Damage radiation effects, Neoplasms, Radiation-Induced genetics, Thyroid Neoplasms genetics
- Abstract
The present study addresses the monitoring of children from the Belorussian and Ukrainian Republics exposed to the fall-out of the Chernobyl accident. Micronucleus analysis has been performed on 56 children from different areas. The micronucleus frequencies in individuals as well as in regional groups were comparable with controls, except for three donors. Such results had to be expected, taking into account that at least 7 years have passed since the accident. Most of the children whose micronucleus frequencies were determined are suffering from thyroid cancer and were treated by radioiodine (131I) therapy. We studied the effect of in vitro exposure with 131I on micronucleus induction and that proliferative ability of lymphocytes. The present investigation indicates that micronuclei can be usefully employed to detect individual exposures to the incorporated radionuclide within several days after the intake of the radionuclide in a dose range of around 65-390 mGy (effective dose).
- Published
- 1996
- Full Text
- View/download PDF
46. Malformations after radiation exposure of preimplantation stages.
- Author
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Streffer C and Müller WU
- Subjects
- Abdominal Muscles abnormalities, Abdominal Muscles embryology, Abdominal Muscles metabolism, Abnormalities, Radiation-Induced genetics, Abnormalities, Radiation-Induced metabolism, Animals, Chromosome Aberrations, Crosses, Genetic, Dose-Response Relationship, Radiation, Embryonic Development genetics, Embryonic Development physiology, Female, Fibroblasts radiation effects, Genome, Male, Mice, Mice, Inbred C57BL, Pregnancy, Proteins metabolism, Skin embryology, Skin radiation effects, Species Specificity, Zygote metabolism, Zygote radiation effects, Abnormalities, Radiation-Induced embryology, Embryonic Development radiation effects
- Abstract
Our studies have shown that, contrary to the opinion in most textbooks, it is possible to increase the number of malformed fetuses in one of our mouse strains (originally "Heiligenberger Stamm", meanwhile HLG/Zte) by radiation exposure of zygotes or of subsequent preimplantation stages. The malformation affected most pronouncedly is gastroschisis, a defect occurring at a frequency of 1 to 4% in the controls. The observed increase is strain specific (C57Bl mice or (HLGxC57Bl)F1 hybrids do not react in the same way), it is accompanied by an increased frequency of chromosomal aberrations in skin fibroblasts and of modified protein patterns in liver, kidney, and skin cells of day 19 fetuses. The most probable explanation seems to be the assumption that radiation exposure of preimplantation stages increases a defect with a genetic predisposition in a specific way and labelizes the genome of subsequent cell generations making these cells more susceptible for noxes acting on the fetus.
- Published
- 1996
47. Comet assay studies indicate that caffeine-mediated increase in radiation risk of embryos is due to inhibition of DNA repair.
- Author
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Müller WU, Bauch T, Wojcik A, Böcker W, and Streffer C
- Subjects
- Animals, DNA drug effects, DNA metabolism, DNA radiation effects, DNA Damage, Embryo, Mammalian metabolism, Female, In Vitro Techniques, Mice, Pregnancy, Risk Factors, Caffeine toxicity, Central Nervous System Stimulants toxicity, DNA Repair drug effects, Embryo, Mammalian drug effects, Embryo, Mammalian radiation effects, Mutagens toxicity
- Abstract
It is well known that under specific conditions caffeine is able to enhance radiation risk of mammalian cells by a factor of approximately 1.5-2. Various mechanisms are discussed in the literature as possible explanations for this interaction. Inhibition of DNA repair plays a crucial role in the discussion, although direct evidence for this assumption is difficult to obtain. We used the "comet assay' in order to analyse the significance of repair inhibition by caffeine in the two-cell stage of mammalian gestation. Our data show that at the concentration necessary for increasing radiation risk (2 mM), caffeine effectively inhibits the restitution of radiation-damaged DNA.
- Published
- 1996
- Full Text
- View/download PDF
48. Induction of malformations by X-ray exposure of various stages of the oogenesis of mice.
- Author
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Müller WU and Schotten H
- Subjects
- Animals, Dose-Response Relationship, Radiation, Female, Mice, Species Specificity, X-Rays, Abnormalities, Radiation-Induced, Oogenesis radiation effects
- Abstract
We studied the effects of ionizing radiation (X-rays, 0-3 Gy, dose rate 1 Gy/min) on various stages of oogenesis of a mouse strain (HLG/Zte) that had been shown previously to respond with an increased number of malformations after radiation exposure of preimplantation stages. Like the results obtained with preimplantation stages, we observed a statistically significant increase in the number of malformed fetuses (exclusively gastroschises) on day 19 of gestation, when oocytes within 1-4 weeks before ovulation were exposed to 2 or 3 Gy. Less mature oocytes were killed by radiation doses of 0.5 Gy and higher. In addition to the increased frequency of malformations, we found a dose-dependent increase of lethal effects (affecting either oocytes or specific gestational stages) and of runts ('dwarfs').
- Published
- 1995
- Full Text
- View/download PDF
49. No indications of an enhanced UV-light-induced unscheduled DNA synthesis in splenocytes of mice following a low-dose irradiation in vivo or in vitro.
- Author
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Wojcik A, Seemayer CA, Müller WU, and Streffer C
- Subjects
- Adaptation, Physiological, Animals, DNA biosynthesis, Female, Lymphocytes metabolism, Mice, Mice, Inbred C57BL, Ultraviolet Rays, DNA Repair, Lymphocytes radiation effects
- Abstract
One of the open questions regarding the adaptive response to ionizing radiation is whether it can be induced in G0 lymphocytes. In the majority of experiments in which an adaptive response in G0 lymphocytes was observed, the adapting dose was applied in vivo. In order to investigate whether there is some in vivo component of adaptive response, mouse splenocytes of the C57BL/6 strain were irradiated with 0.1 Gy x-rays either in vivo or in vitro, and their UV-light-induced unscheduled DNA synthesis (UDS) levels were determined autoradiographically. An augmented UV-light-induced UDS following an adapting dose applied in vivo has previously been described by several authors in splenocytes of C57BL/6 mice, indicating that the adapting dose enhanced the DNA repair capacity of lymphocytes. In the present investigation, however, no evidence of an adaptive response could be seen regardless of whether the adapting dose was given in vivo or in vitro. Those results present a further indication for the fact that the adaptive response to ionizing radiation is not always inducible, even in lymphocytes of an inbred mouse strain in which its existence has been reported before.
- Published
- 1995
- Full Text
- View/download PDF
50. Micronucleus determination as a means to assess radiation exposure.
- Author
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Müller WU, Streffer C, and Wuttke K
- Subjects
- Dose-Response Relationship, Radiation, Fast Neutrons adverse effects, Female, Gamma Rays adverse effects, Humans, Lymphocytes radiation effects, Lymphocytes ultrastructure, Male, Radiation Injuries diagnosis, Radiation Injuries pathology, Radiation Tolerance, Radioisotopes adverse effects, Micronucleus Tests methods, Radiation Injuries etiology, Radioactive Hazard Release
- Abstract
Radiation accidents require an easy to perform and rapid determination of the radiation response of the victim(s) affected by the exposure. Micronuclei in cytochalasin B blocked lymphocytes are able to serve this purpose. Micronuclei are particularly useful when it comes to screening many exposed people after a more or less homogeneous whole body exposure with a high dose rate. There are problems, as is the case for most biological indicators, with partial body (especially when it is due to internal emitters), chronic and fractionated exposure.
- Published
- 1995
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