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Open Access 01-12-2015 | Original research

Gene expression signature in mouse thyroid tissue after ¹³¹I and ²¹¹At exposure

Authors: Nils Rudqvist, Johan Spetz, Emil Schüler, Britta Langen, Toshima Z. Parris, Khalil Helou, Eva Forssell-Aronsson

Published in: EJNMMI Research | Issue 1/2015

Abstract

Background

¹³¹I and ²¹¹At are used in nuclear medicine and accumulate in the thyroid gland and may impact normal thyroid function. The aim of this study was to determine transcriptional profile variations, assess the impact on cellular activity, and identify genes with biomarker properties in thyroid tissue after ¹³¹I and ²¹¹At administration in mice.

Methods

To further investigate thyroid tissue transcriptional responses to ¹³¹I and ²¹¹At administration, we generated a new transcriptional dataset that includes re-evaluated raw intensity values from our previous ¹³¹I and ²¹¹At studies. Differential transcriptional profiles were identified by comparing treated and mock-treated samples using Nexus Expression 3.0 software. Further data analysis was performed using R/Bioconductor and IPA.

Results

A total of 1144 genes were regulated. Hierarchical clustering subdivided the groups into two clusters containing the lowest and highest absorbed dose levels, respectively, and revealed similar transcriptional regulation patterns for many kallikrein-related genes. Twenty-seven of the 1144 genes were recurrently regulated after ¹³¹I and ²¹¹At exposure and divided into six clusters. Several signalling pathways were affected, including calcium, integrin-linked kinase, and thyroid cancer signalling, and the peroxisomal proliferator-activated receptor network.

Conclusions

Substantial changes in transcriptional regulation were shown in ¹³¹I and ²¹¹At-treated samples, and 27 genes were identified as potential biomarkers for ¹³¹I and ²¹¹At exposure. Clustering revealed distinct differences between transcriptional profiles of both similar and different exposures, demonstrating the necessity for better understanding of radiation-induced effects on cellular activity. Additionally, ionizing radiation-induced changes in kallikrein gene expression and identified canonical pathways should be further assessed.

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Title: Gene expression signature in mouse thyroid tissue after 131I and 211At exposure
Authors: Nils Rudqvist
Johan Spetz
Emil Schüler
Britta Langen
Toshima Z. Parris
Khalil Helou
Eva Forssell-Aronsson
Publication date: 01-12-2015
Publisher: Springer Berlin Heidelberg
Published in: EJNMMI Research / Issue 1/2015
Electronic ISSN: 2191-219X
DOI: https://doi.org/10.1186/s13550-015-0137-8

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Gene expression signature in mouse thyroid tissue after ¹³¹I and ²¹¹At exposure

Abstract

Background

Methods

Results

Conclusions

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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