[PMID]: | 29351567 |
[Au] Autor: | Ghandhi SA; Turner HC; Shuryak I; Dugan GO; Bourland JD; Olson JD; Tooze JA; Morton SR; Batinic-Haberle I; Cline JM; Amundson SA |
[Ad] Endereço: | Center for Radiological Research, Columbia University Medical Center, New York, New York, United States of America. |
[Ti] Título: | Whole thorax irradiation of non-human primates induces persistent nuclear damage and gene expression changes in peripheral blood cells. |
[So] Source: | PLoS One;13(1):e0191402, 2018. |
[Is] ISSN: | 1932-6203 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | 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. |
[Mh] Termos MeSH primário: |
Células Sanguíneas/metabolismo Células Sanguíneas/efeitos da radiação Dano ao DNA Expressão Gênica/efeitos da radiação
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[Mh] Termos MeSH secundário: |
Animais Contagem de Células Sanguíneas Aberrações Cromossômicas Relação Dose-Resposta à Radiação Ontologia Genética Seres Humanos Lesão Pulmonar/sangue Lesão Pulmonar/etiologia Lesão Pulmonar/genética Macaca mulatta/sangue Macaca mulatta/genética Masculino Testes para Micronúcleos Lesões Experimentais por Radiação/sangue Lesões Experimentais por Radiação/genética Tórax/efeitos da radiação Fatores de Tempo
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Em] Mês de entrada: | 1803 |
[Cu] Atualização por classe: | 180305 |
[Lr] Data última revisão:
| 180305 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 180120 |
[St] Status: | MEDLINE |
[do] DOI: | 10.1371/journal.pone.0191402 |
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