Long-term radiobiological effects of 131I exposure - dose, age and time related transcriptomatic and proteomic rasponse in rats
Abstract
131I is commonly used in the clinic for treating thyroid diseases, using the physiological uptake of iodine in thyroid, but also for other target tissues. 131I is also commonly released during nuclear accidents. Children are in general more radiation sensitive, and an increased number of thyroid can-cers was seen in children but not in adults after the Chernobyl accident. There us a lack of knowledge about long-term radiobiological mechanisms and response in vivo. The aim of this thesis was to study the 131I induced long-term effects in rat thyroid tissue and plasma by investigating the transcriptional and transla-tional expression, and to propose potential biomarkers related to age at exposure, time after exposure, and dose. The radiation induced transcriptomic and proteomic response was studied in thyroid tissue and plasma from young and adult rats, 3-12 months after 131I injection, using mRNA microarray technique and mass spectrometry. The number of significant transcripts and proteins was in general highest for low doses (5-50 kBq) and for young rats, but showed no general time-related trend. From these transcripts and proteins, biomarker candidates were identified. Biological functions associated to the significant tran-scripts and proteins were identified, and metabolic and hormonal effects were in common in most studies. Young rats demonstrated more affected canonical signaling pathways than adults one year after exposure. In conclusion, radiobiological effects were detected late after exposure (3-12 months), and biomarker candidates (single markers and panels) were proposed for 131I exposure, dose, age, and time after exposure, some con-nected to thyroid function and cancer. The results increases the knowledge in radiobiology, and may be valuable for improvement of radiation therapy and radiation protection.
Parts of work
I. Larsson, M., Rudqvist, N., Spetz, J., Shubbar, E., Parris, TZ., Langen, B., Helou, K., Forssell-Aronsson, E. Long- term transcriptomic and proteomic effects in Sprague Dawley rat thyroid and plasma after internal low dose 131I ex-posure PloS One 2020;15(12):e0244098. ::doi::10.1371/journal.pone.0244098 II. Larsson, M., Rudqvist, N., Spetz, J., Parris, TZ., Langen, B., Helou, K., Forssell-Aronsson, E. Age related long-term response in rat thyroid tissue and plasma after internal low dose exposure to 131I. Submitted III. Larsson, M., Shubbar, E., Spetz, J., Parris, TZ., Langen, B., Berger, E., Helou, K., Forssell-Aronsson, E Late age- and dose-related effects on the proteome of thyroid tissue in rats after 131I exposure. Submitted
Degree
Doctor of Philosophy (Medicine)
University
University of Gothenburg. Sahlgrenska Academy
Institution
Institute of Clinical Sciences. Department of Radiation Physics
Disputation
Onsdag den 14 april 2021, kl 9.00, Hörsal Arvid Carlsson, Academicum, Medicinaregatan 3, Göteborg
Date of defence
2021-04-14
malin.larsson@gu.se
Date
2021-03-23Author
Larsson, Malin
Keywords
radiation
thyroid
plasma
late effects
biomarkers
transcript
protein
Publication type
Doctoral thesis
ISBN
978-91-8009-229-6 (PDF)
978-91-8009-228-9 (TRYCK)
Language
eng