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Transcriptional res...
Transcriptional response in normal mouse tissues after i.v. 211At administration - response related to absorbed dose, dose rate, and time
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- Langen, Britta (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för radiofysik,Sahlgrenska Cancer Center,Institute of Clinical Sciences, Department of Radiation Physics,Chalmers tekniska högskola,Chalmers University of Technology,University of Gothenburg
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- Rudqvist, Nils (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för radiofysik,Sahlgrenska Cancer Center,Institute of Clinical Sciences, Department of Radiation Physics,University of Gothenburg
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- Parris, Toshima Z, 1978 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Sahlgrenska Cancer Center,Institute of Clinical Sciences, Department of Oncology,University of Gothenburg
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- Schüler, Emil (author)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,Institutionen för kliniska vetenskaper, Avdelningen för radiofysik,Institute of Clinical Sciences, Department of Radiation Physics,University of Gothenburg
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- Spetz, Johan (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för radiofysik,Sahlgrenska Cancer Center,Institute of Clinical Sciences, Department of Radiation Physics,University of Gothenburg
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- Helou, Khalil, 1966 (author)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,Institutionen för kliniska vetenskaper, Avdelningen för onkologi,Institute of Clinical Sciences, Department of Oncology,University of Gothenburg
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- Forssell-Aronsson, Eva, 1961 (author)
- Gothenburg University,Göteborgs universitet,Sahlgrenska Cancer Center,Institutionen för kliniska vetenskaper, Avdelningen för radiofysik,Institute of Clinical Sciences, Department of Radiation Physics,University of Gothenburg
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(creator_code:org_t)
- 2015-01-28
- 2015
- English.
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In: EJNMMI Research. - : Springer Science and Business Media LLC. - 2191-219X .- 2191-219X. ; 5:1, s. 1-12
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Abstract
Subject headings
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- 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 211At administration. In order to identify molecular biomarkers of ionizing radiation exposure, we investigated genome-wide transcriptional responses to (very) low mean absorbed doses from 211At in normal mouse tissues. Methods Female BALB/c nude mice were intravenously injected with 1.7 kBq 211At 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 211At 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. Keywords: Astatine-211; Ionizing radiation; Normal tissue response; Radionuclide therapy; Biomarke
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Radiologi och bildbehandling (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Radiology, Nuclear Medicine and Medical Imaging (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Astatine-211
- Ionizing radiation
- Normal tissue response
- Radionuclide therapy
- Biomarker
- Ionizing radiation
Publication and Content Type
- ref (subject category)
- art (subject category)
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