Divergent Molecular and Cellular Responses to Low and High-Dose Ionizing Radiation

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Divergent Molecular and Cellular Responses to Low and High-Dose Ionizing Radiation. / Sampadi, Bharath; Vermeulen, Sylvia; Mišovic, Branislav; Boei, Jan J.; Batth, Tanveer S.; Chang, Jer Gung; Paulsen, Michelle T.; Magnuson, Brian; Schimmel, Joost; Kool, Hanneke; Olie, Cyriel S.; Everts, Bart; Vertegaal, Alfred C.O.; Olsen, Jesper V.; Ljungman, Mats; Jeggo, Penny A.; Mullenders, Leon H.F.; Vrieling, Harry.

In: Cells, Vol. 11, No. 23, 3794, 2022.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Sampadi, B, Vermeulen, S, Mišovic, B, Boei, JJ, Batth, TS, Chang, JG, Paulsen, MT, Magnuson, B, Schimmel, J, Kool, H, Olie, CS, Everts, B, Vertegaal, ACO, Olsen, JV, Ljungman, M, Jeggo, PA, Mullenders, LHF & Vrieling, H 2022, 'Divergent Molecular and Cellular Responses to Low and High-Dose Ionizing Radiation', Cells, vol. 11, no. 23, 3794. https://doi.org/10.3390/cells11233794

APA

Sampadi, B., Vermeulen, S., Mišovic, B., Boei, J. J., Batth, T. S., Chang, J. G., Paulsen, M. T., Magnuson, B., Schimmel, J., Kool, H., Olie, C. S., Everts, B., Vertegaal, A. C. O., Olsen, J. V., Ljungman, M., Jeggo, P. A., Mullenders, L. H. F., & Vrieling, H. (2022). Divergent Molecular and Cellular Responses to Low and High-Dose Ionizing Radiation. Cells, 11(23), [3794]. https://doi.org/10.3390/cells11233794

Vancouver

Sampadi B, Vermeulen S, Mišovic B, Boei JJ, Batth TS, Chang JG et al. Divergent Molecular and Cellular Responses to Low and High-Dose Ionizing Radiation. Cells. 2022;11(23). 3794. https://doi.org/10.3390/cells11233794

Author

Sampadi, Bharath ; Vermeulen, Sylvia ; Mišovic, Branislav ; Boei, Jan J. ; Batth, Tanveer S. ; Chang, Jer Gung ; Paulsen, Michelle T. ; Magnuson, Brian ; Schimmel, Joost ; Kool, Hanneke ; Olie, Cyriel S. ; Everts, Bart ; Vertegaal, Alfred C.O. ; Olsen, Jesper V. ; Ljungman, Mats ; Jeggo, Penny A. ; Mullenders, Leon H.F. ; Vrieling, Harry. / Divergent Molecular and Cellular Responses to Low and High-Dose Ionizing Radiation. In: Cells. 2022 ; Vol. 11, No. 23.

Bibtex

@article{6f0e653326b84651b65194bfcbf8a7f7,
title = "Divergent Molecular and Cellular Responses to Low and High-Dose Ionizing Radiation",
abstract = "Cancer risk after ionizing radiation (IR) is assumed to be linear with the dose; however, for low doses, definite evidence is lacking. Here, using temporal multi-omic systems analyses after a low (LD; 0.1 Gy) or a high (HD; 1 Gy) dose of X-rays, we show that, although the DNA damage response (DDR) displayed dose proportionality, many other molecular and cellular responses did not. Phosphoproteomics uncovered a novel mode of phospho-signaling via S12-PPP1R7, and large-scale dephosphorylation events that regulate mitotic exit control in undamaged cells and the G2/M checkpoint upon IR in a dose-dependent manner. The phosphoproteomics of irradiated DNA double-strand breaks (DSBs) repair-deficient cells unveiled extended phospho-signaling duration in either a dose-dependent (DDR signaling) or independent (mTOR-ERK-MAPK signaling) manner without affecting signal magnitude. Nascent transcriptomics revealed the transcriptional activation of genes involved in NRF2-regulated antioxidant defense, redox-sensitive ERK-MAPK signaling, glycolysis and mitochondrial function after LD, suggesting a prominent role for reactive oxygen species (ROS) in molecular and cellular responses to LD exposure, whereas DDR genes were prominently activated after HD. However, how and to what extent the observed dose-dependent differences in molecular and cellular responses may impact cancer development remain unclear, as the induction of chromosomal damage was found to be dose-proportional (10–200 mGy).",
keywords = "antioxidant response, cell signaling, DNA damage response, ionizing radiation, linear no-threshold, low dose, mitochondria, phosphoproteomics, reactive oxygen species, signal transduction",
author = "Bharath Sampadi and Sylvia Vermeulen and Branislav Mi{\v s}ovic and Boei, {Jan J.} and Batth, {Tanveer S.} and Chang, {Jer Gung} and Paulsen, {Michelle T.} and Brian Magnuson and Joost Schimmel and Hanneke Kool and Olie, {Cyriel S.} and Bart Everts and Vertegaal, {Alfred C.O.} and Olsen, {Jesper V.} and Mats Ljungman and Jeggo, {Penny A.} and Mullenders, {Leon H.F.} and Harry Vrieling",
note = "Publisher Copyright: {\textcopyright} 2022 by the authors.",
year = "2022",
doi = "10.3390/cells11233794",
language = "English",
volume = "11",
journal = "Cells",
issn = "2073-4409",
publisher = "MDPI AG",
number = "23",

}

RIS

TY - JOUR

T1 - Divergent Molecular and Cellular Responses to Low and High-Dose Ionizing Radiation

AU - Sampadi, Bharath

AU - Vermeulen, Sylvia

AU - Mišovic, Branislav

AU - Boei, Jan J.

AU - Batth, Tanveer S.

AU - Chang, Jer Gung

AU - Paulsen, Michelle T.

AU - Magnuson, Brian

AU - Schimmel, Joost

AU - Kool, Hanneke

AU - Olie, Cyriel S.

AU - Everts, Bart

AU - Vertegaal, Alfred C.O.

AU - Olsen, Jesper V.

AU - Ljungman, Mats

AU - Jeggo, Penny A.

AU - Mullenders, Leon H.F.

AU - Vrieling, Harry

N1 - Publisher Copyright: © 2022 by the authors.

PY - 2022

Y1 - 2022

N2 - Cancer risk after ionizing radiation (IR) is assumed to be linear with the dose; however, for low doses, definite evidence is lacking. Here, using temporal multi-omic systems analyses after a low (LD; 0.1 Gy) or a high (HD; 1 Gy) dose of X-rays, we show that, although the DNA damage response (DDR) displayed dose proportionality, many other molecular and cellular responses did not. Phosphoproteomics uncovered a novel mode of phospho-signaling via S12-PPP1R7, and large-scale dephosphorylation events that regulate mitotic exit control in undamaged cells and the G2/M checkpoint upon IR in a dose-dependent manner. The phosphoproteomics of irradiated DNA double-strand breaks (DSBs) repair-deficient cells unveiled extended phospho-signaling duration in either a dose-dependent (DDR signaling) or independent (mTOR-ERK-MAPK signaling) manner without affecting signal magnitude. Nascent transcriptomics revealed the transcriptional activation of genes involved in NRF2-regulated antioxidant defense, redox-sensitive ERK-MAPK signaling, glycolysis and mitochondrial function after LD, suggesting a prominent role for reactive oxygen species (ROS) in molecular and cellular responses to LD exposure, whereas DDR genes were prominently activated after HD. However, how and to what extent the observed dose-dependent differences in molecular and cellular responses may impact cancer development remain unclear, as the induction of chromosomal damage was found to be dose-proportional (10–200 mGy).

AB - Cancer risk after ionizing radiation (IR) is assumed to be linear with the dose; however, for low doses, definite evidence is lacking. Here, using temporal multi-omic systems analyses after a low (LD; 0.1 Gy) or a high (HD; 1 Gy) dose of X-rays, we show that, although the DNA damage response (DDR) displayed dose proportionality, many other molecular and cellular responses did not. Phosphoproteomics uncovered a novel mode of phospho-signaling via S12-PPP1R7, and large-scale dephosphorylation events that regulate mitotic exit control in undamaged cells and the G2/M checkpoint upon IR in a dose-dependent manner. The phosphoproteomics of irradiated DNA double-strand breaks (DSBs) repair-deficient cells unveiled extended phospho-signaling duration in either a dose-dependent (DDR signaling) or independent (mTOR-ERK-MAPK signaling) manner without affecting signal magnitude. Nascent transcriptomics revealed the transcriptional activation of genes involved in NRF2-regulated antioxidant defense, redox-sensitive ERK-MAPK signaling, glycolysis and mitochondrial function after LD, suggesting a prominent role for reactive oxygen species (ROS) in molecular and cellular responses to LD exposure, whereas DDR genes were prominently activated after HD. However, how and to what extent the observed dose-dependent differences in molecular and cellular responses may impact cancer development remain unclear, as the induction of chromosomal damage was found to be dose-proportional (10–200 mGy).

KW - antioxidant response

KW - cell signaling

KW - DNA damage response

KW - ionizing radiation

KW - linear no-threshold

KW - low dose

KW - mitochondria

KW - phosphoproteomics

KW - reactive oxygen species

KW - signal transduction

U2 - 10.3390/cells11233794

DO - 10.3390/cells11233794

M3 - Journal article

C2 - 36497055

AN - SCOPUS:85143652309

VL - 11

JO - Cells

JF - Cells

SN - 2073-4409

IS - 23

M1 - 3794

ER -

ID: 330737074