title: Transcriptional response in normal mouse tissues after i.v. (211)At administration - response related to absorbed dose, dose rate, and time.
abstract: BACKGROUND
  In cancer radiotherapy, knowledge of normal tissue responses and toxicity risks is essential in order to deliver the highest possible absorbed dose to the tumor while maintaining normal tissue exposure at non-critical levels. However, few studies have investigated normal tissue responses in vivo after (211)At administration. In order to identify molecular biomarkers of ionizing radiation exposure, we investigated genome-wide transcriptional responses to (very) low mean absorbed doses from (211)At in normal mouse tissues.
  
  
  METHODS
  Female BALB/c nude mice were intravenously injected with 1.7 kBq (211)At and killed after 1 h, 6 h, or 7 days or injected with 105 or 7.5 kBq and killed after 1 and 6 h, respectively. Controls were mock-treated. Total RNA was extracted from tissue samples of kidney cortex and medulla, liver, lungs, and spleen and subjected to microarray analysis. Enriched biological processes were categorized after cellular function based on Gene Ontology terms.
  
  
  RESULTS
  Responses were tissue-specific with regard to the number of significantly regulated transcripts and associated cellular function. Dose rate effects on transcript regulation were observed with both direct and inverse trends. In several tissues, Angptl4, Per1 and Per2, and Tsc22d3 showed consistent transcript regulation at all exposure conditions.
  
  
  CONCLUSIONS
  This study demonstrated tissue-specific transcriptional responses and distinct dose rate effects after (211)At administration. Transcript regulation of individual genes, as well as cellular responses inferred from enriched transcript data, may serve as biomarkers in vivo. These findings expand the knowledge base on normal tissue responses and may help to evaluate and limit side effects of radionuclide therapy.
authors: Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden ; Department of Applied Physics, Chalmers University of Technology, 412 96 Gothenburg, Sweden.
authors: Britta
authors: B
authors: Langen
authors: Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden.
authors: Nils
authors: N
authors: Rudqvist
authors: Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden.
authors: Toshima Z
authors: TZ
authors: Parris
authors: Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden.
authors: Emil
authors: E
authors: Schüler
authors: Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden.
authors: Johan
authors: J
authors: Spetz
authors: Department of Oncology, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden.
authors: Khalil
authors: K
authors: Helou
authors: Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden.
authors: Eva
authors: E
authors: Forssell-Aronsson
keywords: Astatine-211; Biomarker; Ionizing radiation; Normal tissue response; Radionuclide therapy