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Cytogenetic damage in cells exposed to ionizing radiation under conditions of a changing dose rate
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
Stockholm University, Faculty of Science, Department of Genetics, Microbiology and Toxicology.
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2010 (English)In: Radiation Research, ISSN 0033-7587, Vol. 173, no 3, 283-9 p.Article in journal (Refereed) Published
Abstract [en]

The current international paradigm on the biological effects of radiation is based mainly on the effects of dose with some consideration for the dose rate. No allowance has been made for the potential influence of a changing dose rate (second derivative of dose), and the biological effects of exposing cells to changing dose rates have never been analyzed. This paper provides evidence that radiation effects in cells may depend on temporal changes in the dose rate. In these experiments, cells were moved toward or away from an X-ray source. The speed of movement, the time of irradiation, and the temperature during exposure were controlled. Here we report the results of the first experiments with TK6 cells that were exposed at a constant dose rate, at an increasing dose rate, or at a decreasing dose rate. The average dose rate and the total dose were same for all samples. Micronuclei were scored as the end point. The results show that the level of cytogenetic damage was higher in cells exposed to a decreasing dose rate compared to both an increasing and a constant dose rate. This finding may suggest that the second derivative of dose may influence radiation risk estimates, and the results should trigger further studies on this issue.

Place, publisher, year, edition, pages
2010. Vol. 173, no 3, 283-9 p.
National Category
Natural Sciences
URN: urn:nbn:se:su:diva-38299DOI: 10.1667/RR2012.1ISI: 000275688000003PubMedID: 20199213OAI: diva2:309541
Available from: 2010-04-07 Created: 2010-04-07 Last updated: 2013-11-26Bibliographically approved
In thesis
1. In vitro and in vivo aspects of intrinsic radiosensitivity
Open this publication in new window or tab >>In vitro and in vivo aspects of intrinsic radiosensitivity
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

This thesis focuses on how physical and biological factors influence the outcome of exposures to γ/X-rays. That the dose rate changes during real life exposure scenarios is well-known, but radiobiological data from exposures performed at increasing or decreasing dose rates is lacking. In paper I, it was found that an exposure where the dose rate decreases exponentially induces significantly higher levels of micronuclei in TK6 cells than exposures at an increasing or constant dose rate. Paper II describes the construction and validation of novel exposure equipment used to further study this “decreasing dose rate effect”, which is described in paper III. In paper I we also observed a radioprotective effect when cells were exposed on ice. This “temperature effect” (TE) has been known for decades but it is still not fully understood how hypothermia acts in a radioprotective manner. This was investigated in paper IV, where a multiparametric approach was used to investigate the underlying mechanisms. In paper V the aim was to investigate the role of biomarkers and clinical parameters as possible risk factors for late adverse effects to radiotherapy (RT). This was studied in a rare cohort of head-and-neck cancer patients that developed mandibular osteoradionecrosis (ORN) as a severe late adverse effect of RT. Biomarker measurements and clinical factors were then subjected to multivariate analysis in order to identify ORN risk factors. The results suggest that the patient’s oxidative stress response is an important factor in ORN pathogenesis, and support the current view that patient-related factors constitute the largest source of variation seen in the frequency of late adverse effects to RT.

In summary, this thesis provides new and important insights into the roles of biological and physical factors in determining the consequences of γ/X-ray exposures.

Place, publisher, year, edition, pages
Stockholm: Department of Molecular Biosciences, the Wenner-Gren Institute, 2014. 58 p.
Radiation biology, changing dose rates, cytogenetics, hypothermia, X-rays, radiotherapy, osteoradionecrosis, biomarkers, oxidative stress, individual radiosensitivity
National Category
Biochemistry and Molecular Biology
Research subject
Molecular Biosciences
urn:nbn:se:su:diva-96727 (URN)978-91-7447-821-1 (ISBN)
Public defence
2014-01-10, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 12, Stockholm, 10:00 (English)
Swedish Radiation Safety Authority

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 3: Submitted. Paper 5: Manuscript.

Available from: 2013-12-19 Created: 2013-11-26 Last updated: 2013-12-12Bibliographically approved

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Brehwens, KarlStaaf, ElinaHaghdoost, SiamakWojcik, Andrzej
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