Publications by authors named "Friedo Zölzer"

20 Publications

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Solar Ultraviolet Radiation Risk Estimates-A Comparison of Different Action Spectra and Detector Responsivities.

Int J Environ Res Public Health 2021 05 4;18(9). Epub 2021 May 4.

Federal Institute for Occupational Safety and Health (BAuA), 44149 Dortmund, Germany.

Studies assessing the dose-response relationship for human skin cancer induction by solar ultraviolet radiation (UVR) apply a range of methods to quantify relevant UVR doses, but information about the comparability of these datasets is scarce. We compared biologically weighted effectivities applying the most relevant UVR action spectra in order to test the ability of certain UVR detectors to mimic these biological effects at different times during the day and year. Our calculations were based on solar spectra measured at Dortmund, Germany (51.5° N) and at Townsville, Australia (19.3° S), or computed for latitudes 20° S and 50° N. Convolutions with the CIE action spectra for erythema and non-melanoma skin cancer (NMSC) and with ICNIRP's weighting function showed comparable solar zenith angle (SZA) dependences with little influence of season or latitude. A different SZA dependence was found with Setlow's action spectrum for melanoma induction. Calculations for a number of UVR detector responsivities gave widely discrepant absolute irradiances and doses, which were nevertheless related to those calculated with both CIE spectra by correction factors largely independent of the SZA. Commonly used detectors can thus provide quite accurate estimates of NMSC induction by solar UVR, whereas they may be inadequate to mimic melanoma induction.
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http://dx.doi.org/10.3390/ijerph18094887DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125439PMC
May 2021

Incidence of spontaneous abortions and congenital anomalies in the vicinity of a uranium processing plant.

Cent Eur J Public Health 2020 Mar;28(1):44-47

Institute of Radiology, Toxicology, and Civil Protection, Faculty of Health and Social Sciences, University of South Bohemia in Ceske Budejovice, Ceske Budejovice, Czech Republic.

Objectives: The exposure of embryos or foetuses to ionising radiation can cause serious detriments to health. Thus, an enhanced incidence of spontaneous abortions and congenital anomalies might be expected in the vicinity of a uranium processing plant. We analysed the situation in the vicinity of MAPE Mydlovary, a facility about 20 km from České Budějovice, South Bohemia, Czech Republic, which was in operation from 1963 to 1992.

Methods: No relevant data are available for the period of operation of the uranium processing plant. Statistical data have only been collected since 1994. As sanitation work in the area was initiated at around that time and has yet to be completed, we considered a study of possible prenatal effects in the vicinity of MAPE Mydlovary to still be of interest. Data were provided by the Institute of Health Information and Statistics of the Czech Republic for the years 1994-2013.

Results: We tested whether there are demonstrable, statistically significant differences between the microregions of the four closest villages (Mydlovary, Olešník, Zahájí, and Zliv), the District of České Budějovice, the South-Bohemian Region, and the Czech Republic.

Conclusions: No increase was found in the incidence of spontaneous abortions and congenital anomalies in the vicinity of this former uranium processing plant compared to the surrounding District of České Budějovice, the South Bohemian Region, or the Czech Republic as a whole.
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http://dx.doi.org/10.21101/cejph.a4977DOI Listing
March 2020

Empathy as an ethical principle for environmental health.

Sci Total Environ 2020 Feb 5;705:135922. Epub 2019 Dec 5.

Mensch Innovation, Oxford, United Kingdom.

Purpose: Environmental health ethics is a relatively young field of study, drawing on experience from medical ethics, public health ethics, and the ethics of radiological protection. Fundamental to all of these in one way or another are the four "principles of biomedical ethics", originally proposed by Beauchamp and Childress (1979) as a guide for decision making in clinical practice. Suggestions have been made of various other principles which should be added to address the specifics of the individual disciplines under consideration. Here we are exploring empathy as a principle complementing those hitherto applied in environmental health practice.

Results And Conclusions: Empathy can be defined as the "capability (or disposition) to immerse oneself in and to reflect upon the experiences, perspectives and contexts of others". It is often understood as a skill that one either has or has not, but research has shown it can be taught and therefore can be required as an attitude of those working in health care, education, design, and even politics. We suggest to consider it a procedural principle on a par with inclusiveness, accountability, and transparency. It should drive the assessment of any environmental situation and the health problems accruing from it.
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http://dx.doi.org/10.1016/j.scitotenv.2019.135922DOI Listing
February 2020

Towards a strategic research agenda for social sciences and humanities in radiological protection.

J Radiol Prot 2019 Sep 13;39(3):766-784. Epub 2019 Mar 13.

Belgian Nuclear Research Centre SCK.CEN, Boeretang 200 2400 Mol, Mol, Belgium.

Reflecting a change in funding strategies for European research projects, and a commitment to the idea of responsible research and innovation in radiological protection (RP), a collective of research institutes and universities have developed a prospective Strategic Research Agenda (SRA) for Social Sciences and Humanities (SSH) in radiological protection. This is the first time such a research agenda has been proposed. This paper identifies six research lines of interest and concern: (1) Effects of social, psychological and economic aspects on RP behaviour; (2) Holistic approaches to the governance of radiological risks; (3) Responsible research and innovation in RP; (4) Stakeholder engagement and participatory processes in RP research, development, policy and practice; (5) Risk communication; and (6) RP cultures. These topics were developed through broad stakeholder consultation, in conjunction with activities carried out in the framework of various projects and initiatives (EU H2020 CONCERT programme, the EU FP7 projects OPERRA, PREPARE and EAGLE, the 2015-2018 RICOMET series of conferences, and the 2014 and 2016 International Symposia on Ethics of Environmental Health); as well as through dialogues with members of the European radiation protection research communities. The six research lines open opportunities to integrate a range of key social and ethical considerations into RP, thereby expanding research opportunities and programmes and fostering collaborative approaches to research and innovation.
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http://dx.doi.org/10.1088/1361-6498/ab0f89DOI Listing
September 2019

Adaptation of the human population to the environment: Current knowledge, clues from Czech cytogenetic and "omics" biomonitoring studies and possible mechanisms.

Mutat Res 2017 07 12;773:188-203. Epub 2017 Jul 12.

Department of Genetic Toxicology and Nanotoxicology, Institute of Experimental Medicine, Czech Academy of Sciences, 14220 Prague 4, Czech Republic. Electronic address:

The human population is continually exposed to numerous harmful environmental stressors, causing negative health effects and/or deregulation of biomarker levels. However, studies reporting no or even positive impacts of some stressors on humans are also sometimes published. The main aim of this review is to provide a comprehensive overview of the last decade of Czech biomonitoring research, concerning the effect of various levels of air pollution (benzo[a]pyrene) and radiation (uranium, X-ray examination and natural radon background), on the differently exposed population groups. Because some results obtained from cytogenetic studies were opposite than hypothesized, we have searched for a meaningful interpretation in genomic/epigenetic studies. A detailed analysis of our data supported by the studies of others and current epigenetic knowledge, leads to a hypothesis of the versatile mechanism of adaptation to environmental stressors via DNA methylation settings which may even originate in prenatal development, and help to reduce the resulting DNA damage levels. This hypothesis is fully in agreement with unexpected data from our studies (e.g. lower levels of DNA damage in subjects from highly polluted regions than in controls or in subjects exposed repeatedly to a pollutant than in those without previous exposure), and is also supported by differences in DNA methylation patterns in groups from regions with various levels of pollution. In light of the adaptation hypothesis, the following points may be suggested for future research: (i) the chronic and acute exposure of study subjects should be distinguished; (ii) the exposure history should be mapped including place of residence during the life and prenatal development; (iii) changes of epigenetic markers should be monitored over time. In summary, investigation of human adaptation to the environment, one of the most important processes of survival, is a new challenge for future research in the field of human biomonitoring that may change our view on the results of biomarker analyses and potential negative health impacts of the environment.
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http://dx.doi.org/10.1016/j.mrrev.2017.07.002DOI Listing
July 2017

Radioactivity in mushrooms from selected locations in the Bohemian Forest, Czech Republic.

Radiat Environ Biophys 2017 05 3;56(2):167-175. Epub 2017 Mar 3.

Institute of Radiology, Toxicology and Civil Protection, Faculty of Health and Social Sciences, University of South Bohemia in České Budějovice, J. Boreckého 1167/27, 370 11, Ceske Budejovice, Czech Republic.

Cs is one of the most important radionuclides released in the course of atmospheric nuclear weapon tests and during accidents in nuclear power plants such as that in Chernobyl, Ukraine, or Fukushima, Japan. The aim of this study was to compare Cs and K concentrations in particular species of mushrooms from selected locations in the Bohemian Forest (Czech: Šumava), Czech Republic, where a considerable contamination from the Chernobyl accident had been measured in 1986. Samples were collected between June and October 2014. Activities of Cs and K per dry mass were measured by means of a semiconductor gamma spectrometer. The Cs values measured range from below detection limit to 4300 ± 20 Bq kg, in the case of K from 910 ± 80 to 4300 ± 230 Bq kg. Differences were found between individual locations, due to uneven precipitation in the course of the movement of the radioactive cloud after the Chernobyl accident. There are, however, also differences between individual species of mushrooms from identical locations, which inter alia result from different characteristics of the soil and depths of mycelia. The values measured are compared with established limits and exposures from other radiation sources present in the environment. In general, it can be stated that the values measured are relatively low and the effects on the health of the population are negligible compared to other sources of ionizing radiation.
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http://dx.doi.org/10.1007/s00411-017-0684-7DOI Listing
May 2017

Micronucleus frequency and content in healthy relatives of cancer patients.

Biomarkers 2017 Nov 19;22(7):667-673. Epub 2017 Jan 19.

b Department of Genetic Ecotoxicology , Institute of Experimental Medicine, Academy of Sciences of the Czech Republic , Prague , Czech Republic.

Objective: To compare chromosomal damage in lymphocytes of individuals who did or did not report first-degree relatives with cancer.

Materials And Methods: Cases and controls (68 each) were matched for sex, age and radon exposure. Chromosomal damage was quantified as frequency of micronucleus-containing cells and proportion of centromere-free micronuclei.

Results: Individuals not reporting cancer in their families showed lower values of both the frequency of micronucleus-containing cells (n.s.) and the proportion of centromere-free micronuclei (p < 0.05) in some subgroups, but not in all.

Conclusion: The chromosomal damage observed may be due to inheritable genomic instability, but environmental influences cannot be excluded.
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http://dx.doi.org/10.1080/1354750X.2016.1276627DOI Listing
November 2017

Mapping the factors affecting the frequency and types of micronuclei in an elderly population from Southern Bohemia.

Mutat Res 2016 Nov - Dec;793-794:32-40. Epub 2016 Oct 26.

Institute of Radiology, Toxicology and Civil Protection, University of South Bohemia, 37005 Ceske Budejovice, Czechia.

The micronucleus assay is one of the most common methods used to assess chromosomal damage (losses or breaks) in human peripheral blood lymphocytes (PBL) in genetic toxicology. Most studies have focused on analyzing total micronuclei (MN), but identifying the content of MN can provide more detailed information. The main aim of this study was to map the factors affecting the frequency and types of micronuclei in binucleated cells (BNC) in elderly population. Fluorescence in situ hybridization using Human Pan Centromeric Chromosome Paint was used to identify centromere positive (CEN+) or centromere negative (CEN-) MN. A group of 95 men from Southern Bohemia, Czech Republic (average age 68.0±6.8 years) was followed repeatedly, in spring and fall 2014. The study participants were former workers of the uranium plant "MAPE Mydlovary" (processing uranium ore from 1962 to 1991), and controls. The general profile of individual types of MN, and the effect of the season, former uranium exposure, age, smoking status, weight, and X-ray examination on the level and type of MN were analyzed. The results of this study showed: (i) a stable profile of BNC with MN based on the number of MN during two seasons; (ii) an increase of the number of CEN+ MN from spring to fall; (iii) a lower frequency of the total MN in the exposed group than in controls with a significant difference in the percentage of aberrant cells (%AB.C.) in the fall; (iv) no clear effect of age, smoking and BMI on DNA damage in this group; (v) lower DNA damage levels in former uranium workers who received X-ray examination later in life. In summary, the results indicate a trend of seasonal changes of individual types of MN and suggest that former exposure can have a protective effect on the level of DNA damage in case of future exposure.
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http://dx.doi.org/10.1016/j.mrfmmm.2016.10.004DOI Listing
May 2017

Effective Doses of Employees at the Former Uranium Processing Plant MAPE Mydlovary, Czechoslovakia.

Radiat Prot Dosimetry 2017 Jun;175(2):171-177

Institute of Radiology, Toxicology and Civil Protection, Faculty of Health and Social Sciences, University of South Bohemia in Ceské Budejovice, Božena Nemcová 54, 37001 Ceské Budejovice, Czech Republic.

Results are presented of a survey of almost 1000 dosimetric records of employees at the former uranium processing plant MAPE Mydlovary. Located ~20 km to the north-west of České Budějovice in South Bohemia, it was the place where most of the uranium ore mined in Czechoslovakia in the years from 1962 to 1991 was processed. The records refer to incorporation of short-lived radon progeny and long-lived radionuclides as well as external gamma exposure. The average annual doses calculated from the recorded data were 2.7 ± 1.4, 5.0 ± 3.1 and 1.7 ± 0.9 mSv from these three sources, respectively. Thus, the relative contributions of these components to the effective dose were 29 ± 6, 53 ± 14 and 18 ± 13% , respectively. This is different from the findings in an earlier study for the exposure of uranium miners, where the overall doses were similar, but over 50% was contributed by short-lived radon progeny. No legal limits applicable at the time were exceeded, as the inclusion of long-lived radionuclides in the dose calculations was not yet obligatory.
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http://dx.doi.org/10.1093/rpd/ncw282DOI Listing
June 2017

Pragmatic ethical basis for radiation protection in diagnostic radiology.

Br J Radiol 2016 ;89(1059):20150713

2 Department of Radiology, Toxicology and Civil Protection, Faculty of Health and Social Studies, University of South Bohemia in České Budějovice, České Budějovice, Czech Republic.

Objective: Medical ethics has a tried and tested literature and a global active research community. Even among health professionals, literate and fluent in medical ethics, there is low recognition of radiation protection principles such as justification and optimization. On the other hand, many in healthcare environments misunderstand dose limitation obligations and incorrectly believe patients are protected by norms including a dose limit. Implementation problems for radiation protection in medicine possibly flow from apparent inadequacies of the International Commission on Radiological Protection (ICRP) principles taken on their own, coupled with their failure to transfer successfully to the medical world. Medical ethics, on the other hand, is essentially global, is acceptable in most cultures, is intuitively understood in hospitals, and its expectations are monitored, even by managements. This article presents an approach to ethics in diagnostic imaging rooted in the medical tradition, and alert to contemporary social expectations. ICRP and the International Radiation Protection Association (IRPA), both alert to growing ethical concerns, organized a series of consultations on ethics for general radiation protection in the last few years.

Methods: The literature on medical ethics and implicit ICRP ethical values were reviewed qualitatively, with a view to identifying a system that will help guide contemporary behaviour in radiation protection of patients. Application of the system is illustrated in six clinical scenarios. The proposed system is designed, as far as is possible, so as not to be in conflict with the conclusions emerging from the ICRP/IRPA consultations.

Results And Conclusion: A widely recognized and well-respected system of medical ethics was identified that has global reach and claims acceptance in all cultures. Three values based on this system are grouped with two additional values to provide an ethical framework for application in diagnostic imaging. This system has the potential to be robust and to reach conclusions that are in accord with contemporary medical, social and ethical thinking. The system is not intended to replace the ICRP principles. Rather, it is intended as a well-informed interim approach that will help judge and analyse situations that arouse ethical concerns in radiology. Six scenarios illustrate the practicality of the value system in alerting one to possible deficits in practice.

Advances In Knowledge: Five widely recognized values and the basis for them are identified to support the contemporary practice of diagnostic radiology. These are essential to complement the widely used ICRP principles pending further development in the area.
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http://dx.doi.org/10.1259/bjr.20150713DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4986491PMC
July 2016

Analysis of Genetic Damage in Lymphocytes of Former Uranium Processing Workers.

Cytogenet Genome Res 2015 26;147(1):17-23. Epub 2015 Nov 26.

Department of Radiology, Toxicology and Civil Protection, University of South Bohemia, x010C;eskx00E9; Budx011B;jovice, Czech Republic.

The frequency of cells containing micronuclei (MN) and the presence of centromeres in these MN were analyzed in lymphocytes of 98 men from Southern Bohemia. Forty-six of them had worked at the uranium processing plant 'MAPE Mydlovary' which was closed in 1991, and 52 men were controls from the same area. FISH using human pan-centromeric chromosome paint was employed to detect centromere-positive (CEN+) and -negative (CEN-) MN. A total of 1,000 binucleated cells (BNC) per participant were analyzed after cytochalasin B treatment. All BNC with MN (CEN+ or CEN-) were recorded. No differences were found between formerly exposed workers and the control group, neither in the total frequency of cells with MN per 1,000 BNC (mean levels ± SD, 9.1 ± 3.1 and 9.8 ± 2.5, respectively) nor in the percentage of CEN- MN, which were equal (50 ± 18 and 49 ± 17, respectively). Also, there was no difference between individuals living in the 3 villages closest to the uranium processing plant and those living further away. Considering the fact that effective doses of the workers at MAPE Mydlovary were overall similar to those of former uranium miners in whom higher frequencies of CEN- MN have been found more than 10 years after they had finished working underground, these results are somewhat surprising. A more detailed analysis of the exposures indicates that uranium miners received a greater percentage of their effective dose from the inhalation of radon and its daughters, whereas uranium processing workers received it from the incorporation of long-lived radioactive nuclides such as uranium. If, as has been suggested before, the higher level of DNA damage in miners is due to induced genomic instability, then this phenomenon may be related to radon exposure rather than exposure to uranium.
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http://dx.doi.org/10.1159/000441889DOI Listing
June 2016

Differential S-phase progression after irradiation of p53 functional versus non-functional tumour cells.

Radiol Oncol 2014 Dec 5;48(4):354-60. Epub 2014 Nov 5.

Institute of Medical Radiobiology, Medical Faculty, University Duisburg-Essen, Germany.

Background: Many pathways seem to be involved in the regulation of the intra-S-phase checkpoint after exposure to ionizing radiation, but the role of p53 has proven to be rather elusive. Here we have a closer look at the progression of irradiated cells through S-phase in dependence of their p53 status.

Materials And Methods: Three pairs of tumour cell lines were used, each consisting of one p53 functional and one p53 non-functional line. Cells were labelled with bromodeoxyuridine(BrdU) immediately after irradiation, they were then incubated in label-free medium, and at different times afterwards their position within the S-phase was determined by means of flow cytometry.

Results: While in the p53 deficient cells progression through S-phase was slowed significantly over at least a few hours, it was halted for just about an hour in the p53 proficient cells and then proceeded without further delay or even at a slightly accelerated pace.

Conclusions: It is clear from the experiments presented here that p53 does play a role for the progress of cells through the S-phase after X-ray exposure, but the exact mechanisms by which replicon initiation and elongation is controlled in irradiated cells remain to be elucidated.
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http://dx.doi.org/10.2478/raon-2014-0032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4230555PMC
December 2014

G2-block after irradiation of cells with different p53 status.

Strahlenther Onkol 2014 Oct 14;190(11):1075-9. Epub 2014 Jun 14.

Department of Radiology, Toxicology and Civil Protection, Faculty of Health and Social Studies, University of South Bohemia in České Budějovice, Emy Destinové 46, 37005, České Budějovice, Czech Republic,

Background: Although it is clear that functional p53 is not required for radiation-induced G2 block, certain experimental findings suggest a role for p53 in this context. For instance, as we also confirm here, the maximum accumulation in the G2 compartment after X-ray exposure occurs much later in p53 mutants than in wild types. It remains to be seen, however, whether this difference is due to a longer block in the G2 phase itself.

Material And Methods: We observed the movement of BrdU-labeled cells through G2 and M into G1. From an analysis of the fraction of labeled cells that entered the second posttreatment cell cycle, we were able to determine the absolute duration of the G2 and M phases in unirradiated and irradiated cells.

Results: Our experiments with four cell lines, two melanomas and two squamous carcinomas, showed that the radiation-induced delay of transition through the G2 and M phases did not correlate with p53 status.

Conclusion: We conclude that looking at the accumulation of cells in the G2 compartment alone is misleading when differences in the G2 block are investigated and that the G2 block itself is indeed independent of functional p53.
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http://dx.doi.org/10.1007/s00066-014-0690-5DOI Listing
October 2014

Effect of hypothermia on radiation-induced micronuclei and delay of cell cycle progression in TK6 cells.

Int J Radiat Biol 2014 Apr 19;90(4):318-24. Epub 2014 Mar 19.

Department of Radiobiology and Immunology, Institute of Biology, Jan Kochanowski University , Kielce , Poland.

Purpose: Low temperature (hypothermia) during irradiation leads to a reduced frequency of micronuclei in TK6 cells and it has been suggested that perturbation of cell cycle progression is responsible for this effect. The aim of the study was to test this hypothesis.

Materials And Methods: Human lymphoblastoid TK6 cells were treated by a combination of hypothermia (0.8°C) and ionizing radiation in varying order (hypothermia before, during or after irradiation) and micronuclei were scored. Growth assay and two-dimensional flow cytometry was used to analyze cell cycle kinetics following irradiated of cells at 0.8°C or 37.0°C.

Results: The temperature effect was observed at the level of micronuclei regardless of whether cells were cooled during or immediately before or after the radiation exposure. No indication of cell cycle perturbation by combined exposure to hypothermia and radiation could be detected.

Conclusions: The protective effect of hypothermia observed at the level of cytogenetic damage was not due to a modulation of cell cycle progression. A possible alternative mechanism and experiments to test it are discussed.
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http://dx.doi.org/10.3109/09553002.2014.887233DOI Listing
April 2014

Indicators of oxidative stress after ionizing and/or non-ionizing radiation: superoxid dismutase and malondialdehyde.

J Photochem Photobiol B 2012 Dec 7;117:111-4. Epub 2012 Sep 7.

Southbohemian University in České Budějovice, Faculty of Health and Social Studies, Department of Radiology and Toxicology, Czech Republic.

Several authors have suggested that low level laser light may have a positive influence on side effects caused by ionizing radiation therapy. We therefore studied indicators of oxidative stress after exposure to gamma radiation with or without pre-exposure to low level laser light. Groups of mice were exposed to light from a laser diode at a wavelength of 830 nm, delivering an energy of 20 or 100 J to 1cm(2) in the abdominal part of the animal with a power density of 300 mW/cm(2) in continuous regime. Following this treatment (or sham irradiation), mice were irradiated with graded doses of (60)Co gamma rays. Levels of superoxide dismutase and malondialdehyde were measured in murine blood cells 30 min or 3 days after exposure. For both time points, there was a clear increase of superoxide dismutase and malondialdehyde with gamma dose, but laser light (alone or in combination with gamma irradiation) did not seem to have any influence on either parameter. Because the physical parameters in our experiments were similar to those of studies showing a positive effect of laser pre-exposure, we conclude that the lack of an observed effect in our case was due to differences in biological parameters, i.e. to differences between the tissues or cell types studied. It is also possible, of course, that laser effects would be seen mainly in the skin immediately exposed, and not to the same degree in blood cells circulating through that area, which were exposed to considerably smaller laser energies.
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http://dx.doi.org/10.1016/j.jphotobiol.2012.08.009DOI Listing
December 2012

Micronuclei in lymphocytes from radon spa personnel in the Czech Republic.

Int Arch Occup Environ Health 2013 Aug 7;86(6):629-33. Epub 2012 Jul 7.

Department of Radiology and Toxicology, Faculty of Health and Social Studies, Southbohemian University in České Budějovice, České Budějovice, Czech Republic.

Purpose: To assess the radiation exposure of radon spa personnel in Jáchymov, Czech Republic.

Methods: The frequency of micronucleus-containing cells and the percentage of centromere-free micronuclei (micronuclei containing only acentric fragments) was determined in peripheral blood lymphocytes of 42 individuals working at the Jáchymov spa and 42 control individuals.

Results: There was a highly significant increase in the frequency of micronucleus-containing cells as well as the percentage of centromere-free micronuclei in the lymphocytes of spa personnel versus controls. No individual dosimetry data were available. A comparison with results from currently active uranium miners suggests that the individuals examined at the Jáchymov spa had accumulated effective doses in the order of several tens of mSv, very similar to those of the miners.

Conclusion: The spa personnel in Jáchymov needs to be monitored on an individual level.
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http://dx.doi.org/10.1007/s00420-012-0795-zDOI Listing
August 2013

Micronuclei in lymphocytes from currently active uranium miners.

Radiat Environ Biophys 2012 Aug 24;51(3):277-82. Epub 2012 May 24.

Department of Radiology and Toxicology, Faculty of Health and Social Studies, University of South Bohemia in České Budějovice, České Budějovice, Czech Republic.

Micronuclei can be used as markers of past radiation exposure, but only few studies have dealt with uranium miners. In this paper, we report on micronuclei in lymphocytes from individuals currently working at Rožná, Czech Republic, the last functioning uranium mine in the European Union. A modified micronucleus-centromere test was applied to assess the occurrence of micronuclei in stimulated lymphocytes, as well as their content in terms of whole chromosomes or fragments. Compared with unexposed individuals, the miners had higher frequencies of micronucleus-containing lymphocytes and higher percentages of micronuclei without centromeres, and the differences were significant for both parameters (0.74 ± 0.60 vs. 0.50 ± 0.42, p = 0.017 and 49 ± 44 vs. 12 ± 21, p = 0.0002; means ± standard deviations). There were also significant correlations between one or other of these parameters on the one hand and various dose values on the other, in particular with a 'retrievable' dose, that is, a dose whose effect should still be recognisable in lymphocytes assuming a half-life of 3 years. The 'retrievable' dose at which a doubling of the micronucleus frequency was observed was around 35 mSv, corresponding to a total dose of 90 mSv received while working in the mines. Altogether, our data show that the micronucleus-centromere test is a valuable tool for the assessment of past radiation exposure in uranium miners. The scatter in the data is of course far too great to allow individual dosimetry, but for groups of a few dozen exposed individuals, the method can be used to monitor doses clearly below 100 mSv.
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http://dx.doi.org/10.1007/s00411-012-0422-0DOI Listing
August 2012

Similar extent of apoptosis induction at doses of X-rays and neutrons isoeffective for cell inactivation.

Strahlenther Onkol 2008 May;184(5):270-5

Institute of Medical Radiobiology, University Hospital Essen, Germany.

Background And Purpose: The relative biological effectiveness (RBE) of neutrons differs for various biological endpoints, and for various cell and tissue types. With respect to the apoptosis induction, a whole range of values can be found in the literature, but the decisive factors are not clear. Most previous studies have used apoptosis-prone hematopoietic cells, whereas tumor cells have received little attention. The authors therefore decided to investigate apoptosis induction caused by X-rays and neutrons in a line of human melanoma cells, at doses which are isoeffective for the loss of colony-forming ability.

Material And Methods: Human melanoma cells Be11, expressing p53 wild-type protein, were used throughout. Exponentially growing cells were exposed to two pairs of isoeffective doses (at surviving levels 10% and 1%) of 240-kV X-rays and 5.8-MeV neutrons. 1-8 days after irradiation, the frequency of apoptosis in adherent cells was assessed by two-parameter flow cytometric analysis with a DNA-dye-exclusion annexin-V-binding assay as well as by morphological examination with DAPI staining.

Results: Apoptosis was induced most significantly 6-7 days after irradiation. The time courses, as well as the magnitudes of apoptosis induction, after isoeffective doses of X-rays and neutrons with respect to loss of colony-forming ability appeared to be comparable. RBE values in the range of 4-5 were estimated for apoptosis 4-8 days after irradiation by both the annexin V assay and morphological examination.

Conclusion: Radiation-induced apoptosis depends on ionization density in the same way as cell inactivation in general does, i.e., the RBE is similar, and the ratio of cells dying by apoptosis to cells dying otherwise does not depend on radiation quality.
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http://dx.doi.org/10.1007/s00066-008-1806-6DOI Listing
May 2008

Effects of serum starvation on radiosensitivity, proliferation and apoptosis in four human tumor cell lines with different p53 status.

Strahlenther Onkol 2003 Feb;179(2):99-106

Institute for Medical Radiation Biology, University Hospital Essen, Germany.

Purpose: The effects of serum starvation on radiation sensitivity, cell proliferation and apoptosis were investigated with particular consideration of the p53 status.

Material And Methods: Four human tumor cell lines, Be11 (melanoma, p53 wild-type), MeWo (melanoma, p53 mutant), 4197 (squamous cell carcinoma, p53 wild-type) and 4451 (squamous cell carcinoma, p53 mutant), were used. After the cells had been incubated in starvation medium (0.5% FCS) for 1-6 days, changes in cell cycle distribution, induction of apoptosis and necrosis, and changes in radiation sensitivity were assessed by two-parameter flow cytometric measurements of DNA-dye-exclusion/Annexin V binding, and a conventional colony assay, respectively.

Results: p53 wild-type cell lines showed a decrease in the BrdU labeling index and an increase in the apoptotic cell frequency in starvation medium. p53 mutant cell lines showed a decrease in the BrdU labeling index but no evidence of apoptosis. These cells went into necrosis instead. The radiation sensitivity was increased in 4451 and slightly decreased in Be11 and 4197 in starvation medium.

Conclusion: These data suggest a functional involvement of p53 in starvation-induced G1-block and apoptosis in tumor cells. Altered radiosensitivity after culture in starvation medium seemed to be explained at least in part by the starvation-induced G1-block. The frequency of starvation-induced apoptosis or necrosis was not correlated with radiation sensitivity.
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http://dx.doi.org/10.1007/s00066-003-0973-8DOI Listing
February 2003

Increased radiosensitivity with chronic hypoxia in four human tumor cell lines.

Int J Radiat Oncol Biol Phys 2002 Nov;54(3):910-20

Institut für Medizinische Strahlenbiologie, Universitätsklinikum Essen, Essen, Germany.

Purpose: It is well known that the radiosensitivity of tumor cells can be significantly reduced under hypoxic conditions. However, most of the reports in the literature refer to an experimental setup in which the supply of oxygen is kept low for a short period of time only. In tumors, chronic hypoxia would seem to be the more typical situation, because of an insufficient vascularization and the limited diffusion of oxygen into the tissue. Under such conditions, certain changes in the proliferation patterns of tumor cells, in which the cell cycle checkpoint protein p53 seems to play a role, have been shown to occur. We therefore decided to study radiosensitivity and cell cycle progression under conditions of chronic hypoxia in several human tumor cell lines differing in their p53 status.

Methods And Materials: Four human tumor cell lines (melanomas Be11 and MeWo and squamous carcinomas 4197 and 4451) were incubated for 3 h, 24 h, and 72 h under either oxic or hypoxic conditions and subsequently exposed to graded doses of X-rays. In some cases, cells were kept under hypoxia for the same periods of time, but then reoxygenated immediately before irradiation. Cell survival was assessed with the usual colony formation assay, and cell cycle distributions were determined by two-parameter flow cytometry after labeling with bromodeoxyuridine (BrdU).

Results: As expected, the oxygen enhancement ratio at 3 h was 2.0 or more in all cases. Differences, however, became evident with longer incubation times. At 24 h, the sensitivity of cells kept under hypoxic conditions both before and during irradiation was practically unchanged with cell lines Be11, 4197, and 4451, but clearly increased with MeWo. This resulted in an oxygen enhancement ratio of only 1.1 for the latter cell line when the sensitivity of aerated cells was used as reference. Cells kept under hypoxia for 24 h and reoxygenated shortly before irradiation, however, also showed an increase in sensitivity, so that the oxygen enhancement ratio based on differences in irradiation atmosphere alone was still around 2.0. At 72 h, the two p53 wild-type cell lines were not available for experiments, because they quickly degenerated under hypoxic conditions. Both mutant cell lines now showed similar results, the sensitivity being increased with irradiation under continued hypoxia as well as after reoxygenation. The oxygen enhancement ratios with reference to aerated cells were 1.3 and 1.5 for MeWo and 4451, respectively. Flow cytometric measurements after labeling with BrdU revealed that in all cell lines, the fraction of active S-phase cells during incubation tended to decrease under hypoxic conditions. Only in the p53 mutant cell lines, however, was this accompanied by an increase of the percentage of S-phase cells that were not actively incorporating BrdU.

Conclusions: It is suggested that these quiescent cells in the S-phase compartment develop because of a general breakdown of cellular energy metabolism. In the p53 mutant cells, this may lead to a cessation of cell cycle progression in all phases alike, because checkpoint control has been lost; p53 wild-type cells, on the other hand, settle down preferentially in G(1) under the same conditions. Independently of the p53 status, however, energy depletion may be the cause of a decreased ability to cope with radiation damage and thus the cause of the observed increase in radiosensitivity. This would become more easily apparent in the p53 mutant cell lines, because they are less sensitive than the p53 wild types to hypoxia as such.
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http://dx.doi.org/10.1016/s0360-3016(02)02963-2DOI Listing
November 2002