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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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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 gamma H2AX 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, heavy ions, p53, alternative splicing, immunity, NF-KAPPA-B, SET ENRICHMENT ANALYSIS, GENE-EXPRESSION CHANGES, NORMAL TISSUE-REACTIONS, THYMIDINE KINASE LOCUS, LOW-DOSE RADIATION, SPACE RADIATION, DNA-DAMAGE, HUMAN FIBROBLASTS, TUMOR-SUPPRESSOR

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MLA
Macaeva, Ellina, et al. “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.” FRONTIERS IN ONCOLOGY, vol. 11, 2021, doi:10.3389/fonc.2021.768493.
APA
Macaeva, E., Tabury, K., Michaux, A., Janssen, A., Averbeck, N., Moreels, M., … Quintens, R. (2021). 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. FRONTIERS IN ONCOLOGY, 11. https://doi.org/10.3389/fonc.2021.768493
Chicago author-date
Macaeva, Ellina, Kevin Tabury, Arlette Michaux, Ann Janssen, Nicole Averbeck, Marjan Moreels, Winnok H. De Vos, Sarah Baatout, and Roel Quintens. 2021. “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.” FRONTIERS IN ONCOLOGY 11. https://doi.org/10.3389/fonc.2021.768493.
Chicago author-date (all authors)
Macaeva, Ellina, Kevin Tabury, Arlette Michaux, Ann Janssen, Nicole Averbeck, Marjan Moreels, Winnok H. De Vos, Sarah Baatout, and Roel Quintens. 2021. “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.” FRONTIERS IN ONCOLOGY 11. doi:10.3389/fonc.2021.768493.
Vancouver
1.
Macaeva E, Tabury K, Michaux A, Janssen A, Averbeck N, Moreels M, et al. 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. FRONTIERS IN ONCOLOGY. 2021;11.
IEEE
[1]
E. Macaeva et al., “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,” FRONTIERS IN ONCOLOGY, vol. 11, 2021.
@article{8727982,
  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 gamma H2AX 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}},
  articleno    = {{768493}},
  author       = {{Macaeva, Ellina and Tabury, Kevin and Michaux, Arlette and Janssen, Ann and Averbeck, Nicole and Moreels, Marjan and De Vos, Winnok H. and Baatout, Sarah and Quintens, Roel}},
  issn         = {{2234-943X}},
  journal      = {{FRONTIERS IN ONCOLOGY}},
  keywords     = {{ionizing radiation,gene expression,DNA damage,X-rays,heavy ions,p53,alternative splicing,immunity,NF-KAPPA-B,SET ENRICHMENT ANALYSIS,GENE-EXPRESSION CHANGES,NORMAL TISSUE-REACTIONS,THYMIDINE KINASE LOCUS,LOW-DOSE RADIATION,SPACE RADIATION,DNA-DAMAGE,HUMAN FIBROBLASTS,TUMOR-SUPPRESSOR}},
  language     = {{eng}},
  pages        = {{19}},
  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}},
  url          = {{http://doi.org/10.3389/fonc.2021.768493}},
  volume       = {{11}},
  year         = {{2021}},
}

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