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Micronucleus frequencies and clonogenic cell survival in TK6 cells exposed to changing dose rates under controlled temperature conditions
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. University of Latvia, Latvia.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute. Jan Kochanowski University, Poland.
2014 (English)In: International Journal of Radiation Biology, ISSN 0955-3002, E-ISSN 1362-3095, Vol. 90, no 3, 241-247 p.Article in journal (Refereed) Published
Abstract [en]

Purpose: In most exposure scenarios the dose rate of exposure is not constant. Despite this, very little information exists on the possible biological effects of exposing cells to radiation under the conditions of a changing dose rate. The current study highlights interesting effects following exposure under these conditions.

Materials and methods: We constructed a new exposure facility that allows exposing cells inside an incubator and used it to irradiate human lymphoblastoid TK6 cells both after a moderate (0.48 Gy) and a high (1.1 Gy) dose, where the change in dose rate was, respectively, ≈ 17-fold change (2.2 - 37 mGy/min) and ≈ 39-fold (2.7 - 106 mGy/min). Clonogenic survival and micronuclei (MN) induction were the chosen endpoints.

Results: The obtained results confirm the outcome of our first study that TK6 cells exposed to a decreasing dose rate express more MN than cells exposed to an increasing or constant dose rate. The effect was not seen after the moderate dose of 0.48 Gy or detectable at the level of clonogenic cell survival.

Conclusions: We speculate that the high level of MN is probably related to a delayed elimination of damaged cells by interphase death, as opposed to mechanisms relating to DNA damage and repair.

Place, publisher, year, edition, pages
2014. Vol. 90, no 3, 241-247 p.
Keyword [en]
Changing dose rates, TK6, Micronuclei, Clonogenic survival, X-rays
Keyword [sv]
Skiftande dosrat, röntgenstrålning, mikrokärnor, TK6
National Category
Biochemistry and Molecular Biology
Research subject
Molecular Bioscience
Identifiers
URN: urn:nbn:se:su:diva-96433DOI: 10.3109/09553002.2014.873831ISI: 000332797500005OAI: oai:DiVA.org:su-96433DiVA: diva2:665903
Funder
Swedish Radiation Safety Authority
Available from: 2013-11-21 Created: 2013-11-21 Last updated: 2017-12-06Bibliographically 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.
Keyword
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
Identifiers
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)
Opponent
Supervisors
Funder
Swedish Radiation Safety Authority
Note

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, KarlHaghdoost, SiamakWojcik, Andrzej
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