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A Novel Analysis Method for Evaluating the Interplay of Oxygen and Ionizing Radiation at the Gene Level
Whilst the impact of hypoxia and ionizing radiations on gene expression is well-understood, the interplay of these two effects is not. To better investigate this aspect at the gene level human bladder, brain, lung and prostate cancer cell lines were irradiated with photons (6 Gy, 6 MV LINAC) in hypo...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113813/ https://www.ncbi.nlm.nih.gov/pubmed/33995470 http://dx.doi.org/10.3389/fgene.2021.597635 |
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author | Jansen, Jeannette Vieten, Patricia Pagliari, Francesca Hanley, Rachel Marafioti, Maria Grazia Tirinato, Luca Seco, Joao |
author_facet | Jansen, Jeannette Vieten, Patricia Pagliari, Francesca Hanley, Rachel Marafioti, Maria Grazia Tirinato, Luca Seco, Joao |
author_sort | Jansen, Jeannette |
collection | PubMed |
description | Whilst the impact of hypoxia and ionizing radiations on gene expression is well-understood, the interplay of these two effects is not. To better investigate this aspect at the gene level human bladder, brain, lung and prostate cancer cell lines were irradiated with photons (6 Gy, 6 MV LINAC) in hypoxic and normoxic conditions and prepared for the whole genome analysis at 72 h post-irradiation. The analysis was performed on the obtained 20,000 genes per cell line using PCA and hierarchical cluster algorithms to extract the most dominant genes altered by radiation and hypoxia. With the help of the introduced novel radiation-in-hypoxia and oxygen-impact profiles, it was possible to overcome cell line specific gene regulation patterns. Based on that, 37 genes were found to be consistently regulated over all studied cell lines. All DNA-repair related genes were down-regulated after irradiation, independently of the oxygen state. Cell cycle-dependent genes showed up-regulation consistent with an observed change in cell population in the S and G2/M phases of the cell cycle after irradiation. Genes behaving oppositely in their regulation behavior when changing the oxygen concentration and being irradiated, were immunoresponse and inflammation related genes. The novel analysis method, and by consequence, the results presented here have shown how it is important to consider the two effects together (oxygen and radiation) when analyzing gene response upon cancer radiation treatment. This approach might help to unrevel new gene patterns responsible for cancer radioresistance in patients. |
format | Online Article Text |
id | pubmed-8113813 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81138132021-05-13 A Novel Analysis Method for Evaluating the Interplay of Oxygen and Ionizing Radiation at the Gene Level Jansen, Jeannette Vieten, Patricia Pagliari, Francesca Hanley, Rachel Marafioti, Maria Grazia Tirinato, Luca Seco, Joao Front Genet Genetics Whilst the impact of hypoxia and ionizing radiations on gene expression is well-understood, the interplay of these two effects is not. To better investigate this aspect at the gene level human bladder, brain, lung and prostate cancer cell lines were irradiated with photons (6 Gy, 6 MV LINAC) in hypoxic and normoxic conditions and prepared for the whole genome analysis at 72 h post-irradiation. The analysis was performed on the obtained 20,000 genes per cell line using PCA and hierarchical cluster algorithms to extract the most dominant genes altered by radiation and hypoxia. With the help of the introduced novel radiation-in-hypoxia and oxygen-impact profiles, it was possible to overcome cell line specific gene regulation patterns. Based on that, 37 genes were found to be consistently regulated over all studied cell lines. All DNA-repair related genes were down-regulated after irradiation, independently of the oxygen state. Cell cycle-dependent genes showed up-regulation consistent with an observed change in cell population in the S and G2/M phases of the cell cycle after irradiation. Genes behaving oppositely in their regulation behavior when changing the oxygen concentration and being irradiated, were immunoresponse and inflammation related genes. The novel analysis method, and by consequence, the results presented here have shown how it is important to consider the two effects together (oxygen and radiation) when analyzing gene response upon cancer radiation treatment. This approach might help to unrevel new gene patterns responsible for cancer radioresistance in patients. Frontiers Media S.A. 2021-04-28 /pmc/articles/PMC8113813/ /pubmed/33995470 http://dx.doi.org/10.3389/fgene.2021.597635 Text en Copyright © 2021 Jansen, Vieten, Pagliari, Hanley, Marafioti, Tirinato and Seco. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Jansen, Jeannette Vieten, Patricia Pagliari, Francesca Hanley, Rachel Marafioti, Maria Grazia Tirinato, Luca Seco, Joao A Novel Analysis Method for Evaluating the Interplay of Oxygen and Ionizing Radiation at the Gene Level |
title | A Novel Analysis Method for Evaluating the Interplay of Oxygen and Ionizing Radiation at the Gene Level |
title_full | A Novel Analysis Method for Evaluating the Interplay of Oxygen and Ionizing Radiation at the Gene Level |
title_fullStr | A Novel Analysis Method for Evaluating the Interplay of Oxygen and Ionizing Radiation at the Gene Level |
title_full_unstemmed | A Novel Analysis Method for Evaluating the Interplay of Oxygen and Ionizing Radiation at the Gene Level |
title_short | A Novel Analysis Method for Evaluating the Interplay of Oxygen and Ionizing Radiation at the Gene Level |
title_sort | novel analysis method for evaluating the interplay of oxygen and ionizing radiation at the gene level |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8113813/ https://www.ncbi.nlm.nih.gov/pubmed/33995470 http://dx.doi.org/10.3389/fgene.2021.597635 |
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