High-LET Carbon and Iron Ions Elicit a Prolonged and Amplified p53 Signaling and Inflammatory Response Compared to low-LET X-Rays in Human Peripheral Blood Mononuclear Cells

Understanding the differences in biological response to photon and particle radiation is important for optimal exploitation of particle therapy for cancer patients, as well as for the adequate application of radiation protection measures for astronauts. To address this need, we compared the transcri...

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Autores principales:	Ellina Macaeva, Kevin Tabury, Arlette Michaux, Ann Janssen, Nicole Averbeck, Marjan Moreels, Winnok H. De Vos, Sarah Baatout, Roel Quintens
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	ionizing radiation gene expression DNA damage X-rays heavy ions p53 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/6d08ee8da56640c7878da8d10d1d396e
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spelling	oai:doaj.org-article:6d08ee8da56640c7878da8d10d1d396e2021-11-30T11:31:16ZHigh-LET Carbon and Iron Ions Elicit a Prolonged and Amplified p53 Signaling and Inflammatory Response Compared to low-LET X-Rays in Human Peripheral Blood Mononuclear Cells2234-943X10.3389/fonc.2021.768493https://doaj.org/article/6d08ee8da56640c7878da8d10d1d396e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.768493/fullhttps://doaj.org/toc/2234-943XUnderstanding the differences in biological response to photon and particle radiation is important for optimal exploitation of particle therapy for cancer patients, as well as for the adequate application of radiation protection measures for astronauts. To address this need, we compared the transcriptional profiles of isolated peripheral blood mononuclear cells 8 h after exposure to 1 Gy of X-rays, carbon ions or iron ions with those of non-irradiated cells using microarray technology. All genes that were found differentially expressed in response to either radiation type were up-regulated and predominantly controlled by p53. Quantitative PCR of selected genes revealed a significantly higher up-regulation 24 h after exposure to heavy ions as compared to X-rays, indicating their prolonged activation. This coincided with increased residual DNA damage as evidenced by quantitative γH2AX foci analysis. Furthermore, despite the converging p53 signature between radiation types, specific gene sets related to the immune response were significantly enriched in up-regulated genes following irradiation with heavy ions. In addition, irradiation, and in particular exposure to carbon ions, promoted transcript variation. Differences in basal and iron ion exposure-induced expression of DNA repair genes allowed the identification of a donor with distinct DNA repair profile. This suggests that gene signatures may serve as a sensitive indicator of individual DNA damage repair capacity. In conclusion, we have shown that photon and particle irradiation induce similar transcriptional pathways, albeit with variable amplitude and timing, but also elicit radiation type-specific responses that may have implications for cancer progression and treatmentEllina MacaevaEllina MacaevaEllina MacaevaKevin TaburyKevin TaburyArlette MichauxAnn JanssenNicole AverbeckMarjan MoreelsWinnok H. De VosSarah BaatoutSarah BaatoutRoel QuintensFrontiers Media S.A.articleionizing radiationgene expressionDNA damageX-raysheavy ionsp53Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ionizing radiation gene expression DNA damage X-rays heavy ions p53 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	ionizing radiation gene expression DNA damage X-rays heavy ions p53 Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Ellina Macaeva Ellina Macaeva Ellina Macaeva Kevin Tabury Kevin Tabury Arlette Michaux Ann Janssen Nicole Averbeck Marjan Moreels Winnok H. De Vos Sarah Baatout Sarah Baatout Roel Quintens High-LET Carbon and Iron Ions Elicit a Prolonged and Amplified p53 Signaling and Inflammatory Response Compared to low-LET X-Rays in Human Peripheral Blood Mononuclear Cells
description	Understanding the differences in biological response to photon and particle radiation is important for optimal exploitation of particle therapy for cancer patients, as well as for the adequate application of radiation protection measures for astronauts. To address this need, we compared the transcriptional profiles of isolated peripheral blood mononuclear cells 8 h after exposure to 1 Gy of X-rays, carbon ions or iron ions with those of non-irradiated cells using microarray technology. All genes that were found differentially expressed in response to either radiation type were up-regulated and predominantly controlled by p53. Quantitative PCR of selected genes revealed a significantly higher up-regulation 24 h after exposure to heavy ions as compared to X-rays, indicating their prolonged activation. This coincided with increased residual DNA damage as evidenced by quantitative γH2AX foci analysis. Furthermore, despite the converging p53 signature between radiation types, specific gene sets related to the immune response were significantly enriched in up-regulated genes following irradiation with heavy ions. In addition, irradiation, and in particular exposure to carbon ions, promoted transcript variation. Differences in basal and iron ion exposure-induced expression of DNA repair genes allowed the identification of a donor with distinct DNA repair profile. This suggests that gene signatures may serve as a sensitive indicator of individual DNA damage repair capacity. In conclusion, we have shown that photon and particle irradiation induce similar transcriptional pathways, albeit with variable amplitude and timing, but also elicit radiation type-specific responses that may have implications for cancer progression and treatment
format	article
author	Ellina Macaeva Ellina Macaeva Ellina Macaeva Kevin Tabury Kevin Tabury Arlette Michaux Ann Janssen Nicole Averbeck Marjan Moreels Winnok H. De Vos Sarah Baatout Sarah Baatout Roel Quintens
author_facet	Ellina Macaeva Ellina Macaeva Ellina Macaeva Kevin Tabury Kevin Tabury Arlette Michaux Ann Janssen Nicole Averbeck Marjan Moreels Winnok H. De Vos Sarah Baatout Sarah Baatout Roel Quintens
author_sort	Ellina Macaeva
title	High-LET Carbon and Iron Ions Elicit a Prolonged and Amplified p53 Signaling and Inflammatory Response Compared to low-LET X-Rays in Human Peripheral Blood Mononuclear Cells
title_short	High-LET Carbon and Iron Ions Elicit a Prolonged and Amplified p53 Signaling and Inflammatory Response Compared to low-LET X-Rays in Human Peripheral Blood Mononuclear Cells
title_full	High-LET Carbon and Iron Ions Elicit a Prolonged and Amplified p53 Signaling and Inflammatory Response Compared to low-LET X-Rays in Human Peripheral Blood Mononuclear Cells
title_fullStr	High-LET Carbon and Iron Ions Elicit a Prolonged and Amplified p53 Signaling and Inflammatory Response Compared to low-LET X-Rays in Human Peripheral Blood Mononuclear Cells
title_full_unstemmed	High-LET Carbon and Iron Ions Elicit a Prolonged and Amplified p53 Signaling and Inflammatory Response Compared to low-LET X-Rays in Human Peripheral Blood Mononuclear Cells
title_sort	high-let carbon and iron ions elicit a prolonged and amplified p53 signaling and inflammatory response compared to low-let x-rays in human peripheral blood mononuclear cells
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/6d08ee8da56640c7878da8d10d1d396e
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High-LET Carbon and Iron Ions Elicit a Prolonged and Amplified p53 Signaling and Inflammatory Response Compared to low-LET X-Rays in Human Peripheral Blood Mononuclear Cells

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