Cargando…

Whole thorax irradiation of non-human primates induces persistent nuclear damage and gene expression changes in peripheral blood cells

We investigated the cytogenetic and gene expression responses of peripheral blood cells of non-human primates (NHP, Macaca mulatta) that were whole-thorax irradiated with a single dose of 10 Gy. In this model, partial irradiation of NHPs in the thoracic region (Whole Thorax Lung Irradiation, WTLI) a...

Descripción completa

Detalles Bibliográficos
Autores principales: Ghandhi, Shanaz A., Turner, Helen C., Shuryak, Igor, Dugan, Gregory O., Bourland, J. Daniel, Olson, John D., Tooze, Janet A., Morton, Shad R., Batinic-Haberle, Ines, Cline, J. Mark, Amundson, Sally A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774773/
https://www.ncbi.nlm.nih.gov/pubmed/29351567
http://dx.doi.org/10.1371/journal.pone.0191402
_version_ 1783293807970746368
author Ghandhi, Shanaz A.
Turner, Helen C.
Shuryak, Igor
Dugan, Gregory O.
Bourland, J. Daniel
Olson, John D.
Tooze, Janet A.
Morton, Shad R.
Batinic-Haberle, Ines
Cline, J. Mark
Amundson, Sally A.
author_facet Ghandhi, Shanaz A.
Turner, Helen C.
Shuryak, Igor
Dugan, Gregory O.
Bourland, J. Daniel
Olson, John D.
Tooze, Janet A.
Morton, Shad R.
Batinic-Haberle, Ines
Cline, J. Mark
Amundson, Sally A.
author_sort Ghandhi, Shanaz A.
collection PubMed
description We investigated the cytogenetic and gene expression responses of peripheral blood cells of non-human primates (NHP, Macaca mulatta) that were whole-thorax irradiated with a single dose of 10 Gy. In this model, partial irradiation of NHPs in the thoracic region (Whole Thorax Lung Irradiation, WTLI) allows the study of late radiation-induced lung injury, while avoiding acute radiation syndromes related to hematopoietic and gastrointestinal injury. A transient drop in circulating lymphocytes and platelets was seen by 9 days, followed by elevations in respiratory rate, circulating neutrophils, lymphocytes, and monocytes at 60–100 days, corresponding to computed tomography (CT) and histologic evidence of pneumonitis, and elective euthanasia of four animals. To evaluate long-term DNA damage in NHP peripheral blood lymphocytes after 10 Gy WTLI, we used the cytokinesis-block micronucleus (CBMN) assay to measure chromosomal aberrations as post-mitotic micronuclei in blood samples collected up to 8 months after irradiation. Regression analysis showed significant induction of micronuclei in NHP blood cells that persisted with a gradual decline over the 8-month study period, suggesting long-term DNA damage in blood lymphocytes after WTLI. We also report transcriptomic changes in blood up to 30 days after WTLI. We isolated total RNA from peripheral blood at 3 days before and then at 2, 5 and 30 days after irradiation. We identified 1187 transcripts that were significantly changed across the 30-day time course. From changes in gene expression, we identified biological processes related to immune responses, which persisted across the 30-day study. Response to oxygen-containing compounds and bacteria were implicated by gene-expression changes at the earliest day 2 and latest, day 30 time-points. Gene expression changes suggest a persistent altered state of the immune system, specifically response to infection, for at least a month after WTLI.
format Online
Article
Text
id pubmed-5774773
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-57747732018-02-05 Whole thorax irradiation of non-human primates induces persistent nuclear damage and gene expression changes in peripheral blood cells Ghandhi, Shanaz A. Turner, Helen C. Shuryak, Igor Dugan, Gregory O. Bourland, J. Daniel Olson, John D. Tooze, Janet A. Morton, Shad R. Batinic-Haberle, Ines Cline, J. Mark Amundson, Sally A. PLoS One Research Article We investigated the cytogenetic and gene expression responses of peripheral blood cells of non-human primates (NHP, Macaca mulatta) that were whole-thorax irradiated with a single dose of 10 Gy. In this model, partial irradiation of NHPs in the thoracic region (Whole Thorax Lung Irradiation, WTLI) allows the study of late radiation-induced lung injury, while avoiding acute radiation syndromes related to hematopoietic and gastrointestinal injury. A transient drop in circulating lymphocytes and platelets was seen by 9 days, followed by elevations in respiratory rate, circulating neutrophils, lymphocytes, and monocytes at 60–100 days, corresponding to computed tomography (CT) and histologic evidence of pneumonitis, and elective euthanasia of four animals. To evaluate long-term DNA damage in NHP peripheral blood lymphocytes after 10 Gy WTLI, we used the cytokinesis-block micronucleus (CBMN) assay to measure chromosomal aberrations as post-mitotic micronuclei in blood samples collected up to 8 months after irradiation. Regression analysis showed significant induction of micronuclei in NHP blood cells that persisted with a gradual decline over the 8-month study period, suggesting long-term DNA damage in blood lymphocytes after WTLI. We also report transcriptomic changes in blood up to 30 days after WTLI. We isolated total RNA from peripheral blood at 3 days before and then at 2, 5 and 30 days after irradiation. We identified 1187 transcripts that were significantly changed across the 30-day time course. From changes in gene expression, we identified biological processes related to immune responses, which persisted across the 30-day study. Response to oxygen-containing compounds and bacteria were implicated by gene-expression changes at the earliest day 2 and latest, day 30 time-points. Gene expression changes suggest a persistent altered state of the immune system, specifically response to infection, for at least a month after WTLI. Public Library of Science 2018-01-19 /pmc/articles/PMC5774773/ /pubmed/29351567 http://dx.doi.org/10.1371/journal.pone.0191402 Text en © 2018 Ghandhi et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://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
Ghandhi, Shanaz A.
Turner, Helen C.
Shuryak, Igor
Dugan, Gregory O.
Bourland, J. Daniel
Olson, John D.
Tooze, Janet A.
Morton, Shad R.
Batinic-Haberle, Ines
Cline, J. Mark
Amundson, Sally A.
Whole thorax irradiation of non-human primates induces persistent nuclear damage and gene expression changes in peripheral blood cells
title Whole thorax irradiation of non-human primates induces persistent nuclear damage and gene expression changes in peripheral blood cells
title_full Whole thorax irradiation of non-human primates induces persistent nuclear damage and gene expression changes in peripheral blood cells
title_fullStr Whole thorax irradiation of non-human primates induces persistent nuclear damage and gene expression changes in peripheral blood cells
title_full_unstemmed Whole thorax irradiation of non-human primates induces persistent nuclear damage and gene expression changes in peripheral blood cells
title_short Whole thorax irradiation of non-human primates induces persistent nuclear damage and gene expression changes in peripheral blood cells
title_sort whole thorax irradiation of non-human primates induces persistent nuclear damage and gene expression changes in peripheral blood cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5774773/
https://www.ncbi.nlm.nih.gov/pubmed/29351567
http://dx.doi.org/10.1371/journal.pone.0191402
work_keys_str_mv AT ghandhishanaza wholethoraxirradiationofnonhumanprimatesinducespersistentnucleardamageandgeneexpressionchangesinperipheralbloodcells
AT turnerhelenc wholethoraxirradiationofnonhumanprimatesinducespersistentnucleardamageandgeneexpressionchangesinperipheralbloodcells
AT shuryakigor wholethoraxirradiationofnonhumanprimatesinducespersistentnucleardamageandgeneexpressionchangesinperipheralbloodcells
AT dugangregoryo wholethoraxirradiationofnonhumanprimatesinducespersistentnucleardamageandgeneexpressionchangesinperipheralbloodcells
AT bourlandjdaniel wholethoraxirradiationofnonhumanprimatesinducespersistentnucleardamageandgeneexpressionchangesinperipheralbloodcells
AT olsonjohnd wholethoraxirradiationofnonhumanprimatesinducespersistentnucleardamageandgeneexpressionchangesinperipheralbloodcells
AT toozejaneta wholethoraxirradiationofnonhumanprimatesinducespersistentnucleardamageandgeneexpressionchangesinperipheralbloodcells
AT mortonshadr wholethoraxirradiationofnonhumanprimatesinducespersistentnucleardamageandgeneexpressionchangesinperipheralbloodcells
AT batinichaberleines wholethoraxirradiationofnonhumanprimatesinducespersistentnucleardamageandgeneexpressionchangesinperipheralbloodcells
AT clinejmark wholethoraxirradiationofnonhumanprimatesinducespersistentnucleardamageandgeneexpressionchangesinperipheralbloodcells
AT amundsonsallya wholethoraxirradiationofnonhumanprimatesinducespersistentnucleardamageandgeneexpressionchangesinperipheralbloodcells