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Cellular effects after exposure to mixed beams of ionizing radiation
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology. (Andrzej Wojcik)
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Mixed beams of ionizing radiation in our environment originate from space, the bedrock and our own houses. Radiotherapy patients treated with boron neutron capture therapy or with high energy photons are also exposed to mixed beams of gamma radiation and neutrons. Earlier investigations have reported additivity as well as synergism (a greater than additive response) when combining radiations of different linear energy transfer. However, the outcome seemed to be dependent on the experimental setup, especially the order of irradiation and the temperature at exposure.

A unique facility allowing simultaneously exposure of cells to X-rays and 241Am alpha particles at 37 ºC was constructed and characterized at the Stockholm University (Paper I). To investigate the cytogenetic response to mixed beam irradiation (graded doses of alpha particles, X-rays or a mixture of both) several different cell types were utilized. AA8 Chinese Hamster Ovary cells were analyzed for clonogenic survival (Paper I), human peripheral blood lymphocytes were analyzed for micronuclei and chromosomal aberrations (Paper II and Paper III respectively) and VH10 normal human fibroblasts were scored for gamma-H2AX foci (Paper IV).

For clonogenic survival, mixed beam results were additive, while a significant synergistic effect was observed for micronuclei and chromosomal aberrations. The micronuclei dose responses were linear, and a significant synergistic effect was present at all investigated doses. From the analysis of micronuclei distributions we speculated that the synergistic effect was due to an impaired repair of X-ray induced DNA damage, a conclusion that was supported by chromosomal aberration results. Gamma-H2AX foci dose responses were additive 1 h after exposure, but the kinetics indicated that the presence of low LET-induced damage engages the DNA repair machinery, leading to a delayed repair of the more complex DNA damage induced by alpha particles. These conclusions are not necessary contradictory since fast repair does not necessarily equal correct repair. Taken together, the observed synergistic effects indicate that the risks of stochastic effects from mixed beam exposure may be higher than expected from adding the individual dose components.

Place, publisher, year, edition, pages
Stockholm: Department of Genetics, Microbiology and Toxicology, Stockholm University , 2012. , 55 p.
Keyword [en]
Ionizing radiation, high LET, low LET, mixed beams, combined exposure
National Category
Other Biological Topics Microbiology Biochemistry and Molecular Biology
Research subject
Molecular Genetics
Identifiers
URN: urn:nbn:se:su:diva-80809ISBN: 978-91-7447-588-3 (print)OAI: oai:DiVA.org:su-80809DiVA: diva2:557692
Public defence
2012-11-16, William-Olsson salen, Geovetenskapens hus, Svante Arrhenius väg 14, Stockholm, 10:00 (English)
Opponent
Supervisors
Projects
DNA damage and repair in cells exposed to mixed beams of radiation
Note

At the time of the doctoral defence the following papers were unpublished and had a status as follows: Paper nr 3: Manuscript; Paper nr 4: Manuscript.

Available from: 2012-10-25 Created: 2012-09-28 Last updated: 2012-10-15Bibliographically approved
List of papers
1. Characterisation of a setup for mixed beam exposures of cells to Am-241 alpha particles and X-rays
Open this publication in new window or tab >>Characterisation of a setup for mixed beam exposures of cells to Am-241 alpha particles and X-rays
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2012 (English)In: Radiation Protection Dosimetry, ISSN 0144-8420, E-ISSN 1742-3406, Vol. 151, no 3, 570-579 p.Article in journal (Refereed) Published
Abstract [en]

Exposure of humans to mixed fields of high- and low-linear energy transfer (LET) radiation occurs in many situations—for example, in urban areas with high levels of indoor radon as well as background gamma radiation, during airplane flights or certain forms of radiation therapy. From the perspective of health risk associated with exposure to mixed fields, it is important to understand the interactions between different radiation types. In most cellular investigations on mixed beams, two types of irradiations have been applied sequentially. Simultaneous irradiation is the desirable scenario but requires a dedicated irradiation facility. The authors have constructed a facility where cells can be simultaneously exposed to 241Am alpha particles and 190-kV X-rays at 37°C. This study presents the technical details and the dosimetry of the setup, as well as validates the performance of the setup for clonogenic survival in AA8 Chinese hamster ovary cells. No significant synergistic effect was observed. The relative biological effectiveness of the alpha particles was 2.56 for 37 % and 1.90 for 10 % clonogenic survival.

Keyword
ionizing radiation, high LET, low LET, mixed beams, combined exposure
National Category
Biological Sciences
Research subject
Molecular Genetics
Identifiers
urn:nbn:se:su:diva-80786 (URN)10.1093/rpd/ncs024 (DOI)000308960900023 ()
Projects
DNA damage and repair in cells exposed to mixed beams of radiation
Available from: 2012-09-28 Created: 2012-09-28 Last updated: 2017-12-07Bibliographically approved
2. Micronuclei in human peripheral blood lymphocytes exposed to mixed beams of X-rays and alpha particles
Open this publication in new window or tab >>Micronuclei in human peripheral blood lymphocytes exposed to mixed beams of X-rays and alpha particles
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2012 (English)In: Radiation and Environmental Biophysics, ISSN 0301-634X, E-ISSN 1432-2099, Vol. 51, no 3, 283-293 p.Article in journal (Refereed) Published
Abstract [en]

The purpose of this study was to analyse the cytogenetic effect of exposing human peripheral blood lymphocytes (PBL) to a mixed beam of alpha particles and X-rays. Whole blood collected from one donor was exposed to different doses of alpha particles ((241)Am), X-rays and a combination of both. All exposures were carried out at 37 °C. Three independent experiments were performed. Micronuclei (MN) in binucleated PBL were scored as the endpoint. Moreover, the size of MN was measured. The results show that exposure of PBL to a mixed beam of high and low linear energy transfer radiation led to significantly higher than expected frequencies of MN. The measurement of MN size did not reveal any differences between the effect of alpha particles and mixed beam. In conclusion, a combined exposure of PBL to alpha particles and X-rays leads to a synergistic effect as measured by the frequency of MN. From the analysis of MN distributions, we conclude that the increase was due to an impaired repair of X-ray-induced DNA damage.

Keyword
ionizing radiation, high LET, low LET, mixed beams, combined exposure, micronuclei
National Category
Biological Sciences
Research subject
Molecular Genetics
Identifiers
urn:nbn:se:su:diva-80789 (URN)10.1007/s00411-012-0417-x (DOI)000306694000006 ()
Projects
DNA damage and repair in cells exposed to mixed beams of radiation
Available from: 2012-09-28 Created: 2012-09-28 Last updated: 2017-12-07Bibliographically approved
3. Higher than expected frequencies of complex aberrations in lymphocytes exposed to mixed beams of 241Am alpha particles and X-rays
Open this publication in new window or tab >>Higher than expected frequencies of complex aberrations in lymphocytes exposed to mixed beams of 241Am alpha particles and X-rays
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(English)Manuscript (preprint) (Other academic)
National Category
Other Biological Topics
Research subject
Molecular Genetics
Identifiers
urn:nbn:se:su:diva-80792 (URN)
Projects
DNA damage and repair in cells exposed to mixed beams of radiation
Available from: 2012-09-28 Created: 2012-09-28 Last updated: 2012-09-28Bibliographically approved
4. Gamma-H2AX foci in cells exposed to a mixed beam of X-rays and alpha particles
Open this publication in new window or tab >>Gamma-H2AX foci in cells exposed to a mixed beam of X-rays and alpha particles
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(English)Manuscript (preprint) (Other academic)
Keyword
Ionizing radiation, high LET, low LET, mixed beams, combined exposure, gamma-H2AX
National Category
Other Biological Topics
Research subject
Molecular Genetics
Identifiers
urn:nbn:se:su:diva-80793 (URN)
Projects
DNA damage and repair in cells exposed to mixed beams of radiation
Available from: 2012-09-28 Created: 2012-09-28 Last updated: 2012-09-28Bibliographically approved

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