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Perturbed transcriptional profiles after chronic low dose rate radiation in mice

Adverse health outcomes of ionizing radiation given chronically at low dose rates are highly debated, a controversy also relevant for other stressors. Increased knowledge is needed for a more comprehensive understanding of the damaging potential of ionizing radiation from all dose rates and doses. T...

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Autores principales: Dahl, Hildegunn, Eide, Dag M., Tengs, Torstein, Duale, Nur, Kamstra, Jorke H., Oughton, Deborah H., Olsen, Ann-Karin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384182/
https://www.ncbi.nlm.nih.gov/pubmed/34428250
http://dx.doi.org/10.1371/journal.pone.0256667
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author Dahl, Hildegunn
Eide, Dag M.
Tengs, Torstein
Duale, Nur
Kamstra, Jorke H.
Oughton, Deborah H.
Olsen, Ann-Karin
author_facet Dahl, Hildegunn
Eide, Dag M.
Tengs, Torstein
Duale, Nur
Kamstra, Jorke H.
Oughton, Deborah H.
Olsen, Ann-Karin
author_sort Dahl, Hildegunn
collection PubMed
description Adverse health outcomes of ionizing radiation given chronically at low dose rates are highly debated, a controversy also relevant for other stressors. Increased knowledge is needed for a more comprehensive understanding of the damaging potential of ionizing radiation from all dose rates and doses. There is a lack of relevant low dose rate data that is partly ascribed to the rarity of exposure facilities allowing chronic low dose rate exposures. Using the FIGARO facility, we assessed early (one day post-radiation) and late (recovery time of 100–200 days) hepatic genome-wide transcriptional profiles in male mice of two strains (CBA/CaOlaHsd and C57BL/6NHsd) exposed chronically to a low dose rate (2.5 mGy/h; 1200h, LDR), a mid-dose rate (10 mGy/h; 300h, MDR) and acutely to a high dose rate (100 mGy/h; 30h, HDR) of gamma irradiation, given to an equivalent total dose of 3 Gy. Dose-rate and strain-specific transcriptional responses were identified. Differently modulated transcriptional responses across all dose rate exposure groups were evident by the representation of functional biological pathways. Evidence of changed epigenetic regulation (global DNA methylation) was not detected. A period of recovery markedly reduced the number of differentially expressed genes. Using enrichment analysis to identify the functional significance of the modulated genes, perturbed signaling pathways associated with both cancer and non-cancer effects were observed, such as lipid metabolism and inflammation. These pathways were seen after chronic low dose rate and were not restricted to the acute high dose rate exposure. The transcriptional response induced by chronic low dose rate ionizing radiation suggests contribution to conditions such as cardiovascular diseases. We contribute with novel genome wide transcriptional data highlighting dose-rate-specific radiation responses and emphasize the importance of considering both dose rate, duration of exposure, and variability in susceptibility when assessing risks from ionizing radiation.
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spelling pubmed-83841822021-08-25 Perturbed transcriptional profiles after chronic low dose rate radiation in mice Dahl, Hildegunn Eide, Dag M. Tengs, Torstein Duale, Nur Kamstra, Jorke H. Oughton, Deborah H. Olsen, Ann-Karin PLoS One Research Article Adverse health outcomes of ionizing radiation given chronically at low dose rates are highly debated, a controversy also relevant for other stressors. Increased knowledge is needed for a more comprehensive understanding of the damaging potential of ionizing radiation from all dose rates and doses. There is a lack of relevant low dose rate data that is partly ascribed to the rarity of exposure facilities allowing chronic low dose rate exposures. Using the FIGARO facility, we assessed early (one day post-radiation) and late (recovery time of 100–200 days) hepatic genome-wide transcriptional profiles in male mice of two strains (CBA/CaOlaHsd and C57BL/6NHsd) exposed chronically to a low dose rate (2.5 mGy/h; 1200h, LDR), a mid-dose rate (10 mGy/h; 300h, MDR) and acutely to a high dose rate (100 mGy/h; 30h, HDR) of gamma irradiation, given to an equivalent total dose of 3 Gy. Dose-rate and strain-specific transcriptional responses were identified. Differently modulated transcriptional responses across all dose rate exposure groups were evident by the representation of functional biological pathways. Evidence of changed epigenetic regulation (global DNA methylation) was not detected. A period of recovery markedly reduced the number of differentially expressed genes. Using enrichment analysis to identify the functional significance of the modulated genes, perturbed signaling pathways associated with both cancer and non-cancer effects were observed, such as lipid metabolism and inflammation. These pathways were seen after chronic low dose rate and were not restricted to the acute high dose rate exposure. The transcriptional response induced by chronic low dose rate ionizing radiation suggests contribution to conditions such as cardiovascular diseases. We contribute with novel genome wide transcriptional data highlighting dose-rate-specific radiation responses and emphasize the importance of considering both dose rate, duration of exposure, and variability in susceptibility when assessing risks from ionizing radiation. Public Library of Science 2021-08-24 /pmc/articles/PMC8384182/ /pubmed/34428250 http://dx.doi.org/10.1371/journal.pone.0256667 Text en © 2021 Dahl et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Dahl, Hildegunn
Eide, Dag M.
Tengs, Torstein
Duale, Nur
Kamstra, Jorke H.
Oughton, Deborah H.
Olsen, Ann-Karin
Perturbed transcriptional profiles after chronic low dose rate radiation in mice
title Perturbed transcriptional profiles after chronic low dose rate radiation in mice
title_full Perturbed transcriptional profiles after chronic low dose rate radiation in mice
title_fullStr Perturbed transcriptional profiles after chronic low dose rate radiation in mice
title_full_unstemmed Perturbed transcriptional profiles after chronic low dose rate radiation in mice
title_short Perturbed transcriptional profiles after chronic low dose rate radiation in mice
title_sort perturbed transcriptional profiles after chronic low dose rate radiation in mice
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8384182/
https://www.ncbi.nlm.nih.gov/pubmed/34428250
http://dx.doi.org/10.1371/journal.pone.0256667
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