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Identification of Dbp as a candidate biomarker gene of low-level 131I exposure that affects thyroid function

Konferensbidrag (offentliggjort, men ej förlagsutgivet)
Författare Nils Rudqvist
Johan Spetz
Emil Schüler
Toshima Z Parris
Britta Langen
Khalil Helou
Eva Forssell-Aronsson
Publicerad i 15th International Congress of Radiation Research, Kyoto, Japan, May 25-29
Publiceringsår 2015
Publicerad vid Institutionen för kliniska vetenskaper, Avdelningen för radiofysik
Institutionen för kliniska vetenskaper, Avdelningen för onkologi
Sahlgrenska Cancer Center
Språk en
Ämneskategorier Radiofysik, Strålningsbiologi, Cell- och molekylärbiologi, Medicinsk cellbiologi, Molekylärbiologi

Sammanfattning

131I is frequently used in nuclear medicine. However, unbound or released 131I accumulates in the thyroid gland and may be detrimental to normal thyroid function. The aim of the present study was to identify biomarkers for 131I exposure in rat thyroid tissue and to assess the effect on thyroid function. Thirty-six male Sprague Dawley rats were i.v. injected with 150 µl saline solution containing 9.0, 88, 170, 260, 340, 760, 1300, or 4700 kBq (group A-H) 131I, or mock-treated with 150 µl saline solution, and killed at 24 h after injection. Total RNA was extracted from individual thyroid tissue samples and mRNA levels were determined with the Agilent microarray platform. Nexus Expression 3.0 was used to identify differentially expressed transcripts between irradiated groups and controls. Estimated absorbed dose to thyroid (D) in groups A-H was 0.0058, 0.057, 0.11, 0.17, 0.22, 0.5, 0.8, and 3 Gy, respectively. Totally, 429 transcripts were identified with a fold change ≥ 1.5 and adjusted p-value ≤ 0.01. A trend with downregulation of thyroid hormone biosynthesis associated genes (e.g. thyroglobulin, thyroid peroxidase, the sodium-iodine symporter) was identified, but only statistically significant after 0.0058 and 0.22 Gy. Three transcripts coding for isoform 1 of the DBP protein showed monotonous decrease in downregulation with increasing D up to 0.22 Gy. Change in Dbp expression was not statistically significant for 0.5-3 Gy; however, a trend with downregulation at 0.5 and 0.8 Gy and upregulation at 3 Gy was identified. Previously, 131I (0.85-17 Gy) and 211At (0.023-32 Gy) exposure resulted in upregulation of Dbp in mouse thyroid tissue 24 h after administration. Furthermore, a monotonous decrease in Dbp downregulation was identified in mouse kidney tissue at 8 and 12 months after 177Lu-octreotate administrations (0.13-13 Gy). In conclusion, the Dbp gene is a promising candidate biomarker gene for thyroid exposure to 131I. Further studies should be performed to establish how Dbp expression varies with dose-rate, absorbed dose, and time after administration, and the role of different radiation qualities.

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