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.