In vitro and in vivo aspects of intrinsic radiosensitivity
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
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
Biochemistry and Molecular Biology
Research subject Molecular Biosciences
IdentifiersURN: urn:nbn:se:su:diva-96727ISBN: 978-91-7447-821-1OAI: oai:DiVA.org:su-96727DiVA: diva2:667337
2014-01-10, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 12, Stockholm, 10:00 (English)
Dörr, Wolfgang, Professor
Wojcik, Andrzej, ProfessorHaghdoost, Siamak, Docent
FunderSwedish 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.2013-12-192013-11-262013-12-12Bibliographically approved
List of papers