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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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. / Macaeva, Ellina; Tabury, Kevin; Michaux, Arlette; Averbeck, Nicole; Moreels, Marjan; De Vos, Winnok H.; Baatout, Sarah; Quintens, Roel.

In: Frontiers in Oncology, Vol. 11, 768493, 23.11.2021, p. 1-19.

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Macaeva, Ellina ; Tabury, Kevin ; Michaux, Arlette ; Averbeck, Nicole ; Moreels, Marjan ; De Vos, Winnok H. ; Baatout, Sarah ; Quintens, Roel. / 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. In: Frontiers in Oncology. 2021 ; Vol. 11. pp. 1-19.

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@article{529d3ac80dcb4ee1a2a0caecfeb6e5ae,
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",
abstract = "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",
keywords = "Ionizing radiation, Gene expression, DNA damage, X-rays, p53, Alternative splicing, Immunity",
author = "Ellina Macaeva and Kevin Tabury and Arlette Michaux and Nicole Averbeck and Marjan Moreels and {De Vos}, {Winnok H.} and Sarah Baatout and Roel Quintens",
note = "Score=10",
year = "2021",
month = nov,
day = "23",
doi = "10.3389/fonc.2021.768493",
language = "English",
volume = "11",
pages = "1--19",
journal = "Frontiers in Oncology",
issn = "2234-943X",
publisher = "Frontiers Media SA",

}

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TY - JOUR

T1 - 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

AU - Macaeva, Ellina

AU - Tabury, Kevin

AU - Michaux, Arlette

AU - Averbeck, Nicole

AU - Moreels, Marjan

AU - De Vos, Winnok H.

AU - Baatout, Sarah

AU - Quintens, Roel

N1 - Score=10

PY - 2021/11/23

Y1 - 2021/11/23

N2 - 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

AB - 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

KW - Ionizing radiation

KW - Gene expression

KW - DNA damage

KW - X-rays

KW - p53

KW - Alternative splicing

KW - Immunity

UR - https://ecm.sckcen.be/OTCS/llisapi.dll?func=ll&objId=46435222&objAction=download

U2 - 10.3389/fonc.2021.768493

DO - 10.3389/fonc.2021.768493

M3 - Article

VL - 11

SP - 1

EP - 19

JO - Frontiers in Oncology

JF - Frontiers in Oncology

SN - 2234-943X

M1 - 768493

ER -

ID: 7288883