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Adaptive responses to low doses of radiation or chemicals: their cellular and molecular mechanisms

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Abstract

This article reviews the current knowledge on the mechanisms of adaptive response to low doses of ionizing radiation or chemical exposure. A better knowledge of these mechanisms is needed to improve our understanding of health risks at low levels of environmental or occupational exposure and their involvement in cancer or non-cancer diseases. This response is orchestrated through a multifaceted cellular program involving the concerted action of diverse stress response pathways. These evolutionary highly conserved defense mechanisms determine the cellular response to chemical and physical aggression. They include DNA damage repair (p53, ATM, PARP pathways), antioxidant response (Nrf2 pathway), immune/inflammatory response (NF-κB pathway), cell survival/death pathway (apoptosis), endoplasmic response to stress (UPR response), and other cytoprotective processes including autophagy, cell cycle regulation, and the unfolded protein response. The coordinated action of these processes induced by low-dose radiation or chemicals produces biological effects that are currently estimated with the linear non-threshold model. These effects are controversial. They are difficult to detect because of their low magnitude, the scarcity of events in humans, and the difficulty of corroborating associations over the long term. Improving our understanding of these biological consequences should help humans and their environment by enabling better risk estimates, the revision of radiation protection standards, and possible therapeutic advances.

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Fig. 1

(adapted from [185])

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Abbreviations

AhR:

Aryl hydrocarbon receptor

Akt:

Protein kinase B

ARE:

Antioxidant responsive element

ATM:

Ataxia telangiectasia mutated

CDK:

Cyclin-dependent kinases

DSB:

Double-strand break

DNA-PK:

DNA-dependent protein kinase

ER:

Endoplasmic reticulum

ERK:

Extracellular signal-regulating kinase

IR:

Ionizing radiation

JNK:

c-Jun N-terminal kinases

MAPK:

Mitogen-activated protein kinase

miRNA:

Micro RNA

NF-κB:

Nuclear factor-kappa B

Nfr2:

NF-E2-related 2 (transcription factor)

NMDR:

Non-monotonic dose-response

PERK:

Protein kinase R-like endoplasmic reticulum kinase

ROS:

Reactive oxygen species

TGF-β:

Transforming growth factor beta

UPR:

Unfolded protein response

XIAP:

X-linked inhibitor of apoptosis

XRE:

Xenobiotic responsive element

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Acknowledgements

We apologize to the many scientists whose work we were not able to credit due to space restrictions. We thank Joan Francesc Barquinero Estruch (Universitat Autònoma de Barcelona), Klervi Leuraud, Karine Tack and Dominique Laurier (Department of research on the biological and health effects of ionizing radiation, IRSN) for helpful comments and suggestions and Marc Benderitter (Department of research in radiobiology and regenerative medicine, IRSN) for initial discussions on this topic.

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  1. Institut de Radioprotection et de Sureté Nucléaire (IRSN), PSE-SANTE, SESANE, LRTOX, B.P. no 17, 92262, Fontenay-aux-Roses Cedex, France

    Yann Guéguen, Alice Bontemps & Teni G. Ebrahimian

  2. Institut de Radioprotection et de Sureté Nucléaire (IRSN), PSE-SANTE, SESANE, LRSI, Fontenay-aux-Roses, France

    Yann Guéguen

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  1. Yann Guéguen
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  2. Alice Bontemps
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Correspondence to Yann Guéguen.

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Guéguen, Y., Bontemps, A. & Ebrahimian, T.G. Adaptive responses to low doses of radiation or chemicals: their cellular and molecular mechanisms. Cell. Mol. Life Sci. 76, 1255–1273 (2019). https://doi.org/10.1007/s00018-018-2987-5

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  • DOI: https://doi.org/10.1007/s00018-018-2987-5

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