Nils Rudqvist1, Emil Schüler2, Toshima Z Parris3, Britta Langen2, Khalil Helou3, Eva Forssell-Aronsson4. 1. Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden. Electronic address: nils.rudqvist@radfys.gu.se. 2. Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden. 3. Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden. 4. Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden; Department of Medical Physics and Medical Bioengineering, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden.
Abstract
INTRODUCTION: In the present investigation, microarray analysis was used to monitor transcriptional activity in thyroids in mice 24 h after (131)I exposure. The aims of this study were to 1) assess the transcriptional patterns associated with (131)I exposure in normal mouse thyroid tissue and 2) propose biomarkers for (131)I exposure of the thyroid. METHODS: Adult BALB/c nude mice were i.v. injected with 13, 130 or 260 kBq of (131)I and killed 24h after injection (absorbed dose to thyroid: 0.85, 8.5, or 17 Gy). Mock-treated mice were used as controls. Total RNA was extracted from thyroids and processed using the Illumina platform. RESULTS: In total, 497, 546, and 90 transcripts were regulated (fold change ≥1.5) in the thyroid after 0.85, 8.5, and 17 Gy, respectively. These were involved in several biological functions, e.g. oxygen access, inflammation and immune response, and apoptosis/anti-apoptosis. Approximately 50% of the involved transcripts at each absorbed dose level were dose-specific, and 18 transcripts were commonly detected at all absorbed dose levels. The Agpat9, Plau, Prf1, and S100a8 gene expression displayed a monotone decrease in regulation with absorbed dose, and further studies need to be performed to evaluate if they may be useful as dose-related biomarkers for 131I exposure. CONCLUSION: Distinct and substantial differences in gene expression and affected biological functions were detected at the different absorbed dose levels. The transcriptional profiles were specific for the different absorbed dose levels. We propose that the Agpat9, Plau, Prf1, and S100a8 genes might be novel potential absorbed dose-related biomarkers to (131)I exposure of thyroid. ADVANCES IN KNOWLEDGE: During the recent years, genomic techniques have been developed; however, they have not been fully utilized in nuclear medicine and radiation biology. We have used RNA microarrays to investigate genome-wide transcriptional regulations in thyroid tissue in mice after low, intermediate, and high absorbed doses from (131)I exposure in vivo. Using this approach, we have identified novel biological responses and potential absorbed dose-related biomarkers to (131)I exposure. Our research shows the importance of embracing technological advances and multi-disciplinary collaboration in order to apply them in radiation therapy, nuclear medicine, and radiation biology. IMPLICATIONS ON PATIENT CARE: This work may contribute with new knowledge of potential normal tissue effects or complications that may occur after exposure to ionizing radiation in diagnostic and therapeutic nuclear medicine, and due to radioactive fallout or accident with radionuclide spread.
INTRODUCTION: In the present investigation, microarray analysis was used to monitor transcriptional activity in thyroids in mice 24 h after (131)I exposure. The aims of this study were to 1) assess the transcriptional patterns associated with (131)I exposure in normal mouse thyroid tissue and 2) propose biomarkers for (131)I exposure of the thyroid. METHODS: Adult BALB/c nude mice were i.v. injected with 13, 130 or 260 kBq of (131)I and killed 24h after injection (absorbed dose to thyroid: 0.85, 8.5, or 17 Gy). Mock-treated mice were used as controls. Total RNA was extracted from thyroids and processed using the Illumina platform. RESULTS: In total, 497, 546, and 90 transcripts were regulated (fold change ≥1.5) in the thyroid after 0.85, 8.5, and 17 Gy, respectively. These were involved in several biological functions, e.g. oxygen access, inflammation and immune response, and apoptosis/anti-apoptosis. Approximately 50% of the involved transcripts at each absorbed dose level were dose-specific, and 18 transcripts were commonly detected at all absorbed dose levels. The Agpat9, Plau, Prf1, and S100a8 gene expression displayed a monotone decrease in regulation with absorbed dose, and further studies need to be performed to evaluate if they may be useful as dose-related biomarkers for 131I exposure. CONCLUSION: Distinct and substantial differences in gene expression and affected biological functions were detected at the different absorbed dose levels. The transcriptional profiles were specific for the different absorbed dose levels. We propose that the Agpat9, Plau, Prf1, and S100a8 genes might be novel potential absorbed dose-related biomarkers to (131)I exposure of thyroid. ADVANCES IN KNOWLEDGE: During the recent years, genomic techniques have been developed; however, they have not been fully utilized in nuclear medicine and radiation biology. We have used RNA microarrays to investigate genome-wide transcriptional regulations in thyroid tissue in mice after low, intermediate, and high absorbed doses from (131)I exposure in vivo. Using this approach, we have identified novel biological responses and potential absorbed dose-related biomarkers to (131)I exposure. Our research shows the importance of embracing technological advances and multi-disciplinary collaboration in order to apply them in radiation therapy, nuclear medicine, and radiation biology. IMPLICATIONS ON PATIENT CARE: This work may contribute with new knowledge of potential normal tissue effects or complications that may occur after exposure to ionizing radiation in diagnostic and therapeutic nuclear medicine, and due to radioactive fallout or accident with radionuclide spread.
Authors: Britta Langen; Nils Rudqvist; Toshima Z Parris; Emil Schüler; Johan Spetz; Khalil Helou; Eva Forssell-Aronsson Journal: EJNMMI Res Date: 2015-01-28 Impact factor: 3.138
Authors: Nils Rudqvist; Johan Spetz; Emil Schüler; Toshima Z Parris; Britta Langen; Khalil Helou; Eva Forssell-Aronsson Journal: PLoS One Date: 2015-07-15 Impact factor: 3.240
Authors: Emil Schüler; Maria Larsson; Toshima Z Parris; Martin E Johansson; Khalil Helou; Eva Forssell-Aronsson Journal: PLoS One Date: 2015-08-19 Impact factor: 3.240
Authors: Nils Rudqvist; Johan Spetz; Emil Schüler; Toshima Z Parris; Britta Langen; Khalil Helou; Eva Forssell-Aronsson Journal: PLoS One Date: 2017-02-21 Impact factor: 3.240
Authors: Nils Rudqvist; Johan Spetz; Emil Schüler; Britta Langen; Toshima Z Parris; Khalil Helou; Eva Forssell-Aronsson Journal: EJNMMI Res Date: 2015-10-22 Impact factor: 3.138