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| Status |
Public on Apr 22, 2014 |
| Title |
Biological events associated with 99mTcO4--mediated thyroid stunning effect |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Rationale: Auger electrons bear a low energy (0-10 keV) which is deposited in a very small volume (a few nm3) around the site of emission. From a radio-toxicological point of view, the effects of Auger electrons on normal tissues are largely unknown, understudied and generally assumed negligible. In this context, the discovery that the Auger electron emitter 99mTc can induce stunning on primary thyrocytes in vitro, at low doses, is intriguing. Extrapolated in vivo, this observation suggests that, a radioisotope as commonly used in nuclear medicine as 99mTc may significantly influence thyroid biology. The aim of the present study was to evaluate the absorbed dose of 99mTc pertechnetate (99mTcO4−) required to induce thyroid stunning in vivo and to analyse the biological events associated/concomitant with this effect. Methods: SPECT/CT imaging of thyroid uptake of 99mTcO4− was used to demonstrate stunning effect in mice and quantitative analysis of the images was used for dosimetric calculations. The biological effects associated with this phenomenon were evaluated by Western blotting, quantitative RT-PCR, histology, immuno-histochmistry and global gene expression pattern analysis. Results: Auger electrons-mediated thyroid stunning can be observed in vivo, in mouse thyroid. The threshold of the absorbed dose to the thyroid required to obtain a significant stunning effect is in the range of 20 Gy. This effect is associated with a reduction in the levels of functional Na/I symporter (NIS) protein without any significant cell death. It is reversible within days. At the cellular level, a decrease in NIS mRNA, the activation of the p53 pathway and the generation of double-strand DNA breaks can be observed. Conclusion: Auger electrons emitted by 99mTc can induce thyroid stunning in vivo, in mice but the thyroid needs to be exposed to a dose of at least 20 Gy, a dose unlikely to be encountered in the clinical practice. Nevertheless, this report represents, to our knowledge, the first example of a significant action of Auger electrons on a normal tissue, in vivo and provides a unique experimental set-up to understand the fine molecular mechanisms involved in the biological effects of Auger electrons.
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| Overall design |
One color design, corresponding to 2 conditions performed on 4 mice: TcO4- (Tc)-treated versus Control (Ct) mice for a total of 8 samples.
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| Contributor(s) |
Vassaux G, Mari B, Barbry P, Lebrigand K |
| Citation(s) |
24663284 |
| Submission date |
Apr 29, 2013 |
| Last update date |
Jul 19, 2017 |
| Contact name |
Kevin Lebrigand |
| Organization name |
IPMC/CNRS
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| Lab |
Functional Genomics Platform of Nice-Sophia-Antipolis, France.
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| Street address |
660 route des lucioles
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| City |
Valbonne - Sophia-Antipolis |
| ZIP/Postal code |
06560 |
| Country |
France |
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| Platforms (1) |
| GPL13912 |
Agilent-028005 SurePrint G3 Mouse GE 8x60K Microarray (Feature Number version) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA200575 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE46470_RAW.tar |
104.5 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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