Transcriptional response in normal mouse tissues after i.v. 211At administration - response related to absorbed dose, dose rate, and time
Artikel i vetenskaplig tidskrift, 2015

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

Ionizing radiation

Radionuclide therapy

Astatine-211

Biomarker

Normal tissue response

Författare

Britta Langen

Chalmers, Teknisk fysik, Nukleär teknik

Göteborgs universitet

Nils Rudqvist

Göteborgs universitet

Toshima Z Parris

Göteborgs universitet

Emil Schüler

Göteborgs universitet

Johan Spetz

Göteborgs universitet

Khalil Helou

Göteborgs universitet

Eva Forssell-Aronsson

Göteborgs universitet

EJNMMI Research

2191-219X (ISSN)

Vol. 5 1 1-12

Ämneskategorier

Biokemi och molekylärbiologi

Cell- och molekylärbiologi

Radiologi och bildbehandling

Cancer och onkologi

DOI

10.1186/s13550-014-0078-7

PubMed

25853007

Mer information

Skapat

2017-10-07