⁹⁹mTcO₄--, auger-mediated thyroid stunning: dosimetric requirements and associated molecular events.

Low-energy Auger and conversion electrons deposit their energy in a very small volume (a few nm3) around the site of emission. From a radiotoxicological point of view the effects of low-energy electrons on normal tissues are largely unknown, understudied, and generally assumed to be negligible. In t...

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Autores principales:	Béatrice Cambien, Philippe R Franken, Audrey Lamit, Thibault Mauxion, Peggy Richard-Fiardo, Julien Guglielmi, Lydie Crescence, Bernard Mari, Thierry Pourcher, Jacques Darcourt, Manuel Bardiès, Georges Vassaux
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7c5cd35ab412487c91840e045769a99f
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spelling	oai:doaj.org-article:7c5cd35ab412487c91840e045769a99f2021-11-18T08:26:35Z⁹⁹mTcO₄--, auger-mediated thyroid stunning: dosimetric requirements and associated molecular events.1932-620310.1371/journal.pone.0092729https://doaj.org/article/7c5cd35ab412487c91840e045769a99f2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24663284/?tool=EBIhttps://doaj.org/toc/1932-6203Low-energy Auger and conversion electrons deposit their energy in a very small volume (a few nm3) around the site of emission. From a radiotoxicological point of view the effects of low-energy electrons on normal tissues are largely unknown, understudied, and generally assumed to be negligible. In this context, the discovery that the low-energy electron emitter, 99mTc, can induce stunning on primary thyrocytes in vitro, at low absorbed doses, is intriguing. Extrapolated in vivo, this observation suggests that a radioisotope as commonly used in nuclear medicine as 99mTc may significantly influence thyroid physiology. The aims of this study were to determine whether 99mTc pertechnetate (99mTcO4-) is capable of inducing thyroid stunning in vivo, to evaluate the absorbed dose of 99mTcO4- required to induce this stunning, and to analyze the biological events associated/concomitant with this effect. Our results show that 99mTcO4--mediated thyroid stunning can be observed in vivo in mouse thyroid. The threshold of the absorbed dose in the thyroid required to obtain a significant stunning effect is in the range of 20 Gy. This effect is associated with a reduced level of functional Na/I symporter (NIS) protein, with no significant cell death. It is reversible within a few days. At the cellular and molecular levels, a decrease in NIS mRNA, the generation of double-strand DNA breaks, and the activation of the p53 pathway are observed. Low-energy electrons emitted by 99mTc can, therefore, induce thyroid stunning in vivo in mice, if it is exposed to an absorbed dose of at least 20 Gy, a level unlikely to be encountered in clinical practice. Nevertheless this report presents an unexpected effect of low-energy electrons on a normal tissue in vivo, and provides a unique experimental setup to understand the fine molecular mechanisms involved in their biological effects.Béatrice CambienPhilippe R FrankenAudrey LamitThibault MauxionPeggy Richard-FiardoJulien GuglielmiLydie CrescenceBernard MariThierry PourcherJacques DarcourtManuel BardièsGeorges VassauxPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 3, p e92729 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Béatrice Cambien Philippe R Franken Audrey Lamit Thibault Mauxion Peggy Richard-Fiardo Julien Guglielmi Lydie Crescence Bernard Mari Thierry Pourcher Jacques Darcourt Manuel Bardiès Georges Vassaux ⁹⁹mTcO₄--, auger-mediated thyroid stunning: dosimetric requirements and associated molecular events.
description	Low-energy Auger and conversion electrons deposit their energy in a very small volume (a few nm3) around the site of emission. From a radiotoxicological point of view the effects of low-energy electrons on normal tissues are largely unknown, understudied, and generally assumed to be negligible. In this context, the discovery that the low-energy electron emitter, 99mTc, can induce stunning on primary thyrocytes in vitro, at low absorbed doses, is intriguing. Extrapolated in vivo, this observation suggests that a radioisotope as commonly used in nuclear medicine as 99mTc may significantly influence thyroid physiology. The aims of this study were to determine whether 99mTc pertechnetate (99mTcO4-) is capable of inducing thyroid stunning in vivo, to evaluate the absorbed dose of 99mTcO4- required to induce this stunning, and to analyze the biological events associated/concomitant with this effect. Our results show that 99mTcO4--mediated thyroid stunning can be observed in vivo in mouse thyroid. The threshold of the absorbed dose in the thyroid required to obtain a significant stunning effect is in the range of 20 Gy. This effect is associated with a reduced level of functional Na/I symporter (NIS) protein, with no significant cell death. It is reversible within a few days. At the cellular and molecular levels, a decrease in NIS mRNA, the generation of double-strand DNA breaks, and the activation of the p53 pathway are observed. Low-energy electrons emitted by 99mTc can, therefore, induce thyroid stunning in vivo in mice, if it is exposed to an absorbed dose of at least 20 Gy, a level unlikely to be encountered in clinical practice. Nevertheless this report presents an unexpected effect of low-energy electrons on a normal tissue in vivo, and provides a unique experimental setup to understand the fine molecular mechanisms involved in their biological effects.
format	article
author	Béatrice Cambien Philippe R Franken Audrey Lamit Thibault Mauxion Peggy Richard-Fiardo Julien Guglielmi Lydie Crescence Bernard Mari Thierry Pourcher Jacques Darcourt Manuel Bardiès Georges Vassaux
author_facet	Béatrice Cambien Philippe R Franken Audrey Lamit Thibault Mauxion Peggy Richard-Fiardo Julien Guglielmi Lydie Crescence Bernard Mari Thierry Pourcher Jacques Darcourt Manuel Bardiès Georges Vassaux
author_sort	Béatrice Cambien
title	⁹⁹mTcO₄--, auger-mediated thyroid stunning: dosimetric requirements and associated molecular events.
title_short	⁹⁹mTcO₄--, auger-mediated thyroid stunning: dosimetric requirements and associated molecular events.
title_full	⁹⁹mTcO₄--, auger-mediated thyroid stunning: dosimetric requirements and associated molecular events.
title_fullStr	⁹⁹mTcO₄--, auger-mediated thyroid stunning: dosimetric requirements and associated molecular events.
title_full_unstemmed	⁹⁹mTcO₄--, auger-mediated thyroid stunning: dosimetric requirements and associated molecular events.
title_sort	⁹⁹mtco₄--, auger-mediated thyroid stunning: dosimetric requirements and associated molecular events.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/7c5cd35ab412487c91840e045769a99f
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⁹⁹mTcO₄--, auger-mediated thyroid stunning: dosimetric requirements and associated molecular events.

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