title: Dose-specific transcriptional responses in thyroid tissue in mice after (131)I administration.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
  
  
  CONCLUSIONS
  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.
  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.affiliation: 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.
authors.forename: Nils
authors.initials: N
authors.lastname: Rudqvist
authors.affiliation: Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden.
authors.forename: Emil
authors.initials: E
authors.lastname: Schüler
authors.affiliation: Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden.
authors.forename: Toshima Z
authors.initials: TZ
authors.lastname: Parris
authors.affiliation: Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden.
authors.forename: Britta
authors.initials: B
authors.lastname: Langen
authors.affiliation: Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden.
authors.forename: Khalil
authors.initials: K
authors.lastname: Helou
authors.affiliation: 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.
authors.forename: Eva
authors.initials: E
authors.lastname: Forssell-Aronsson
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D063990:Gene Ontology; D007457:Iodine Radioisotopes / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D013961:Thyroid Gland / Q000378:metabolism* / Q000528:radiation effects*; D013997:Time Factors; D014158:Transcription, Genetic / Q000528:radiation effects*
chemical_list: D015415:Biomarkers; D007457:Iodine Radioisotopes
keywords: (131)I; Global transcriptional gene regulation; Normal thyroid gland; Radiation biology; Radionuclide therapy