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EJNMMI Research

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Open Access 01-12-2012 | Original research

Transcriptional response of BALB/c mouse thyroids following in vivo astatine-211 exposure reveals distinct gene expression profiles

Authors: Nils Rudqvist, Toshima Z Parris, Emil Schüler, Khalil Helou, Eva Forssell-Aronsson

Published in: EJNMMI Research | Issue 1/2012

Abstract

Background

Astatine-211 (²¹¹At) is an alpha particle emitting halogen with almost optimal linear energy transfer for creating DNA double-strand breaks and is thus proposed for radionuclide therapy when bound to tumor-seeking agents. Unbound ²¹¹At accumulates in the thyroid gland, and the concept of basal radiation-induced biological effects in the thyroid tissue is, to a high degree, unknown and is most valuable.

Methods

Female BALB/c nude mice were intravenously injected with 0.064 to 42 kBq of ²¹¹At, resulting in absorbed doses of 0.05 to 32 Gy in the thyroid gland. Thyroids were removed 24 h after injection; total RNA was extracted from pooled thyroids and processed in triplicate using Illumina MouseRef-8 Whole-Genome Expression Beadchips.

Results

Thyroids exposed to ²¹¹At revealed distinctive gene expression profiles compared to non-irradiated controls. A larger number of genes were affected at low absorbed doses (0.05 and 0.5 Gy) compared to intermediate (1.4 Gy) and higher absorbed doses (11 and 32 Gy). The proportion of dose-specific genes increased with decreased absorbed dose. Additionally, 1.4 Gy often exerted opposite regulation on gene expression compared to the other absorbed doses. Using Gene Ontology data, an immunological effect was detected at 0.05 and 11 Gy. Effects on cellular response to external stress and cell cycle regulation and proliferation were detected at 1.4 and 11 Gy.

Conclusions

Conclusively, the cellular response to ionizing radiation is complex and differs with absorbed dose. The response acquired at high absorbed doses cannot be extrapolated down to low absorbed doses or vice versa. We also demonstrated that the thyroid - already at absorbed doses similar to those obtained in radionuclide therapy - responds with expression of a high number of genes. Due to the increased heterogeneous irradiation at low absorbed doses, we suggest that this response partly originates from non-irradiated cells in the tissue, i.e., bystander cells.

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Title: Transcriptional response of BALB/c mouse thyroids following in vivo astatine-211 exposure reveals distinct gene expression profiles
Authors: Nils Rudqvist
Toshima Z Parris
Emil Schüler
Khalil Helou
Eva Forssell-Aronsson
Publication date: 01-12-2012
Publisher: Springer Berlin Heidelberg
Published in: EJNMMI Research / Issue 1/2012
Electronic ISSN: 2191-219X
DOI: https://doi.org/10.1186/2191-219X-2-32

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Transcriptional response of BALB/c mouse thyroids following in vivo astatine-211 exposure reveals distinct gene expression profiles

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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