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Low doses of γ-radiation induce consistent protein expression changes in human leukocytes
Stockholm University, Faculty of Science, Department of Molecular Biology and Functional Genomics.
Karolinska University Hospital.
Uppsala University.
Karolinska University Hospital.
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2011 (English)In: International Journal of Low Radiation, ISSN 1477-6545, Vol. 8, no 5/6, 374-387 p.Article in journal (Refereed) Published
Abstract [en]

Twenty percent of cancer patients experience adverse effects after radiotherapy. The therapeutic doses are adjusted to the most sensitive individuals, resulting in a suboptimal dose for many patients. At present there is no screening system available to predict individual radiosensitivity. The main aim of this study is to investigate differences in protein expression pathways induced by low doses of radiation in whole blood obtained from radiosensitive and non–radiosensitive patients. To address this aim, a protocol for exposure condition, dose and analysis of whole blood was developed. The conditions for handling blood samples were optimised. The optimal doses and post irradiation conditions were determined. We found that 1 mGy and 150 mGy significantly changed protein expression in leukocytes collected from the two donors. The result shows that the protocol developed is suitable for characterisation of proteomic profiles associated with low dose exposure of leukocytes.

Place, publisher, year, edition, pages
Inderscience Publishers, 2011. Vol. 8, no 5/6, 374-387 p.
Keyword [en]
low dose radiation; Oxidative stress; proteomics; whole blood; gamma radiation
National Category
Cell Biology Other Biological Topics
Research subject
Molecular Biology
URN: urn:nbn:se:su:diva-97111DOI: 10.1504/IJLR.2011.047188OAI: diva2:675479
Swedish Radiation Safety AuthoritySwedish Cancer Society
Available from: 2013-12-03 Created: 2013-12-03 Last updated: 2013-12-05Bibliographically approved
In thesis
1. Radiation induced biomarkers of individual sensitivity to radiation therapy
Open this publication in new window or tab >>Radiation induced biomarkers of individual sensitivity to radiation therapy
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Fifty percent of solid cancers are treated with radiation therapy (RT). The dose used in RT is adjusted to the most sensitive individuals so that not more than 5% of the patients will have severe adverse healthy tissue effects. As a consequence, the majority of the patients will receive a suboptimal dose, as they would have tolerated a higher total dose and received a better tumor control. Thus, if RT could be individualized based on radiation sensitivity (RS), more patients would be cured and the most severe adverse reactions could be avoided. At present the mechanisms behind RS are not known.

The long term aim of this thesis was to develop diagnostic tools to assess the individual RS of breast cancer patients and to better understand the mechanisms behind the RS and radiation effects after low dose exposures. The approach was based on the hypothesis that biomarkers of individual RS, in terms of acute adverse skin reactions after breast cancer RT, can be found in whole blood that has been stressed by low doses of ionizing radiation (IR). 

To reach this goal two different approaches to identify biomarkers of RS have been investigated. A protocol for the analysis of differential protein expression in response to low dose in vitro irradiated whole blood was developed (paper I). This protocol was then used to investigate the proteomic profile of radiation sensitive and normo-sensitive patients, using isotope-coded protein labeled proteomics (ICPL). The results from the ICPL study (paper III) show that the two patient groups have different protein expression profiles both at the basal level and after IR. In paper II the potential biomarker 8-oxo-dG was investigated in serum after IR. The relative levels of IR induced 8-oxo-dG from radiation sensitive patients differ significantly from normo-sensitive patients. This indicates that the sensitive patients differ in their cellular response to IR and that 8-oxo-dG is a potential biomarker for RS.

Place, publisher, year, edition, pages
Stockholm: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 2014. 42 p.
low dose ionizing radiation, radiation sensitivity, proteomics, whole blood, 8-oxo-dG, oxidative stress, acute adverse healthy tissue effects
National Category
Biochemistry and Molecular Biology
Research subject
Molecular Bioscience
urn:nbn:se:su:diva-97123 (URN)978-91-7447-824-2 (ISBN)
Public defence
2014-01-31, William-Olssonsalen, Geovetenskapens hus, Svante Arrhenius väg 14, Stockholm, 10:00 (English)

At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manuscript.

Available from: 2014-01-09 Created: 2013-12-04 Last updated: 2015-03-10Bibliographically approved

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Skiöld, SaraHarms-Ringdahl, MatsHaghdoost, Siamak
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