Cellular and Molecular Life Sciences

, Volume 76, Issue 7, pp 1255–1273 | Cite as

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

  • Yann GuéguenEmail author
  • Alice Bontemps
  • Teni G. Ebrahimian


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.


Adaptive response Low-dose Signaling pathway Stress response Epigenetic regulation Defense mechanism 



Aryl hydrocarbon receptor


Protein kinase B


Antioxidant responsive element


Ataxia telangiectasia mutated


Cyclin-dependent kinases


Double-strand break


DNA-dependent protein kinase


Endoplasmic reticulum


Extracellular signal-regulating kinase


Ionizing radiation


c-Jun N-terminal kinases


Mitogen-activated protein kinase


Micro RNA


Nuclear factor-kappa B


NF-E2-related 2 (transcription factor)


Non-monotonic dose-response


Protein kinase R-like endoplasmic reticulum kinase


Reactive oxygen species


Transforming growth factor beta


Unfolded protein response


X-linked inhibitor of apoptosis


Xenobiotic responsive element



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.

Compliance with ethical standards

Conflict of interest

The authors declare they have no conflict of interest.


  1. 1.
    BEIRVII (2006) Health risks from exposure to low levels of ionizing radiation. Committee to Assess Health Risks from Exposure to Low Levels of Ionizing Radiation, National Research Council (U.S.). The National Academies PressGoogle Scholar
  2. 2.
    Acad. Sci. (Paris) (2005) Dose-effect relationship and estimation of the carcinogenic effects of low doses of ionizing radiation. Joint Report of the Académie des Sciences (Paris)—Académie Nationale de MédecineGoogle Scholar
  3. 3.
    UNSCEAR (2012) Biological mechanisms of radiation actions at low doses—a white paper to guide the Scientific Committee’s future programme of work. United Nations, New YorkGoogle Scholar
  4. 4.
    UNSCEAR (2008) United Nations Scientific Committee on the Effects of Atomic Radiation. Sources and Effects of Ionizing Radiation. Volume I: Report to the General Assembly, Scientific Annexes A and B; Volume II: Scientific Annexes C, D and E. United Nations Scientific Committee on the Effects of Atomic Radiation. UNSCEAR 2008 Report. United Nations Sales publications E.10.XI.3. United Nations, New YorkGoogle Scholar
  5. 5.
    Tang FR, Loke WK (2015) Molecular mechanisms of low dose ionizing radiation-induced hormesis, adaptive responses, radioresistance, bystander effects, and genomic instability. Int J Radiat Biol 91(1):13–27. CrossRefPubMedGoogle Scholar
  6. 6.
    Heidenreich WF, Paretzke HG, Jacob P (1997) No evidence for increased tumor rates below 200 mSv in the atomic bomb survivors data. Radiat Environ Biophys 36(3):205–207CrossRefPubMedGoogle Scholar
  7. 7.
    Hoel DG, Li P (1998) Threshold models in radiation carcinogenesis. Health Phys 75(3):241–250CrossRefPubMedGoogle Scholar
  8. 8.
    Lagarde F, Beausoleil C, Belcher SM, Belzunces LP, Emond C, Guerbet M, Rousselle C (2015) Non-monotonic dose-response relationships and endocrine disruptors: a qualitative method of assessment. Environ Health 14:13. CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Olivieri G, Bodycote J, Wolff S (1984) Adaptive response of human lymphocytes to low concentrations of radioactive thymidine. Science 223(4636):594–597CrossRefPubMedGoogle Scholar
  10. 10.
    Matsumoto H, Hamada N, Takahashi A, Kobayashi Y, Ohnishi T (2007) Vanguards of paradigm shift in radiation biology: radiation-induced adaptive and bystander responses. J Radiat Res 48(2):97–106CrossRefPubMedGoogle Scholar
  11. 11.
    Feinendegen LE, Brooks AL, Morgan WF (2011) Biological consequences and health risks of low-level exposure to ionizing radiation: commentary on the workshop. Health Phys 100(3):247–259. CrossRefPubMedGoogle Scholar
  12. 12.
    Calabrese EJ, Baldwin LA (2003) Hormesis: the dose-response revolution. Annu Rev Pharmacol Toxicol 43:175–197. CrossRefPubMedGoogle Scholar
  13. 13.
    Tubiana M, Feinendegen LE, Yang C, Kaminski JM (2009) The linear no-threshold relationship is inconsistent with radiation biologic and experimental data. Radiology 251(1):13–22. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Pallet N, Anglicheau D, Thervet E (2009) Autophagy is an adaptative mechanism against endoplasmic reticulum stress. Nephrol Dial Transplant 24(12):3891. (author reply 3891) CrossRefPubMedGoogle Scholar
  15. 15.
    Barouki R (2010) Linking long-term toxicity of xeno-chemicals with short-term biological adaptation. Biochimie 92(9):1222–1226. CrossRefPubMedGoogle Scholar
  16. 16.
    Andreau K, Leroux M, Bouharrour A (2012) Health and cellular impacts of air pollutants: from cytoprotection to cytotoxicity. Biochem Res Int 2012:493894. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    UNSCEAR (1994) Sources and effects of ionizing radiation, United Nations Scientific Committee on the Effects of Atomic Radiation. Report to the General Assembly, with Scientific Annexes. ANNEX B, Adaptive responses to radiation in cells and organisms. United Nations, New YorkGoogle Scholar
  18. 18.
    Calabrese EJ, Baldwin LA (2001) The frequency of U-shaped dose responses in the toxicological literature. Toxicol Sci 62(2):330–338CrossRefPubMedGoogle Scholar
  19. 19.
    Szumiel I (2015) Ionizing radiation-induced oxidative stress, epigenetic changes and genomic instability: the pivotal role of mitochondria. Int J Radiat Biol 91(1):1–12. CrossRefPubMedGoogle Scholar
  20. 20.
    Tapio S, Jacob V (2007) Radioadaptive response revisited. Radiat Environ Biophys 46(1):1–12. CrossRefPubMedGoogle Scholar
  21. 21.
    Rigaud O, Moustacchi E (1996) Radioadaptation for gene mutation and the possible molecular mechanisms of the adaptive response. Mutat Res 358(2):127–134CrossRefPubMedGoogle Scholar
  22. 22.
    Sthijns MM, Weseler AR, Bast A, Haenen GR (2016) Time in redox adaptation processes: from evolution to hormesis. Int J Mol Sci 17(10):1649. CrossRefPubMedCentralGoogle Scholar
  23. 23.
    Calabrese EJ (2013) Hormetic mechanisms. Crit Rev Toxicol 43(7):580–606. CrossRefPubMedGoogle Scholar
  24. 24.
    Jennings P, Limonciel A, Felice L, Leonard MO (2013) An overview of transcriptional regulation in response to toxicological insult. Arch Toxicol 87(1):49–72. CrossRefPubMedGoogle Scholar
  25. 25.
    Wink S, Hiemstra S, Huppelschoten S, Danen E, Niemeijer M, Hendriks G, Vrieling H, Herpers B, van de Water B (2014) Quantitative high content imaging of cellular adaptive stress response pathways in toxicity for chemical safety assessment. Chem Res Toxicol 27(3):338–355. CrossRefPubMedGoogle Scholar
  26. 26.
    Harper JW, Elledge SJ (2007) The DNA damage response: ten years after. Mol Cell 28(5):739–745. CrossRefPubMedGoogle Scholar
  27. 27.
    Sasaki MS, Ejima Y, Tachibana A, Yamada T, Ishizaki K, Shimizu T, Nomura T (2002) DNA damage response pathway in radioadaptive response. Mutat Res 504(1–2):101–118CrossRefPubMedGoogle Scholar
  28. 28.
    Nenoi M, Wang B, Vares G (2015) In vivo radioadaptive response: a review of studies relevant to radiation-induced cancer risk. Hum Exp Toxicol 34(3):272–283. CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Samson L, Schwartz JL (1980) Evidence for an adaptive DNA repair pathway in CHO and human skin fibroblast cell lines. Nature 287(5785):861–863CrossRefPubMedGoogle Scholar
  30. 30.
    Barquinero JF, Barrios L, Caballin MR, Miro R, Ribas M, Subias A, Egozcue J (1995) Occupational exposure to radiation induces an adaptive response in human lymphocytes. Int J Radiat Biol 67(2):187–191CrossRefPubMedGoogle Scholar
  31. 31.
    Joiner MC, Lambin P, Marples B (1999) Adaptive response and induced resistance. C R Acad Sci III 322(2–3):167–175CrossRefPubMedGoogle Scholar
  32. 32.
    Wiencke JK, Afzal V, Olivieri G, Wolff S (1986) Evidence that the [3H]thymidine-induced adaptive response of human lymphocytes to subsequent doses of X-rays involves the induction of a chromosomal repair mechanism. Mutagenesis 1(5):375–380CrossRefPubMedGoogle Scholar
  33. 33.
    Wolff S (1992) Failla memorial lecture. Is radiation all bad? The search for adaptation. Radiat Res 131(2):117–123CrossRefPubMedGoogle Scholar
  34. 34.
    Le XC, Xing JZ, Lee J, Leadon SA, Weinfeld M (1998) Inducible repair of thymine glycol detected by an ultrasensitive assay for DNA damage. Science 280(5366):1066–1069CrossRefPubMedGoogle Scholar
  35. 35.
    Coleman MA, Yin E, Peterson LE, Nelson D, Sorensen K, Tucker JD, Wyrobek AJ (2005) Low-dose irradiation alters the transcript profiles of human lymphoblastoid cells including genes associated with cytogenetic radioadaptive response. Radiat Res 164(4 Pt 1):369–382CrossRefPubMedGoogle Scholar
  36. 36.
    Takahashi A, Asakawa I, Yuki K, Matsumoto T, Kumamoto M, Kondo N, Ohnishi K, Tachibana A, Ohnishi T (2002) Radiation-induced apoptosis in the scid mouse spleen after low dose-rate irradiation. Int J Radiat Biol 78(8):689–693. CrossRefPubMedGoogle Scholar
  37. 37.
    Nosel I, Vaurijoux A, Barquinero JF, Gruel G (2013) Characterization of gene expression profiles at low and very low doses of ionizing radiation. DNA Repair (Amst) 12(7):508–517. CrossRefGoogle Scholar
  38. 38.
    Mitchel RE (2015) Adaption by low dose radiation exposure: a look at scope and limitations for radioprotection. Dose Response. CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Wang X, Ohnishi T (1997) p53-dependent signal transduction induced by stress. J Radiat Res 38(3):179–194CrossRefPubMedGoogle Scholar
  40. 40.
    Shimizu T, Kato T Jr, Tachibana A, Sasaki MS (1999) Coordinated regulation of radioadaptive response by protein kinase C and p38 mitogen-activated protein kinase. Exp Cell Res 251(2):424–432. CrossRefPubMedGoogle Scholar
  41. 41.
    Boreham DR, Mitchel RE (1991) DNA lesions that signal the induction of radioresistance and DNA repair in yeast. Radiat Res 128(1):19–28CrossRefPubMedGoogle Scholar
  42. 42.
    Iyer R, Lehnert BE (2002) Alpha-particle-induced increases in the radioresistance of normal human bystander cells. Radiat Res 157(1):3–7CrossRefPubMedGoogle Scholar
  43. 43.
    Lee JM, Li J, Johnson DA, Stein TD, Kraft AD, Calkins MJ, Jakel RJ, Johnson JA (2005) Nrf2, a multi-organ protector? FASEB J 19(9):1061–1066. CrossRefPubMedGoogle Scholar
  44. 44.
    Osburn WO, Kensler TW (2008) Nrf2 signaling: an adaptive response pathway for protection against environmental toxic insults. Mutat Res 659(1–2):31–39. CrossRefPubMedGoogle Scholar
  45. 45.
    Khan NM, Sandur SK, Checker R, Sharma D, Poduval TB, Sainis KB (2011) Pro-oxidants ameliorate radiation-induced apoptosis through activation of the calcium-ERK1/2-Nrf2 pathway. Free Radic Biol Med 51(1):115–128. CrossRefPubMedGoogle Scholar
  46. 46.
    Mathew ST, Bergstrom P, Hammarsten O (2014) Repeated Nrf2 stimulation using sulforaphane protects fibroblasts from ionizing radiation. Toxicol Appl Pharmacol 276(3):188–194. CrossRefPubMedGoogle Scholar
  47. 47.
    Xing X, Zhang C, Shao M, Tong Q, Zhang G, Li C, Cheng J, Jin S, Ma J, Wang G, Li X, Cai L (2012) Low-dose radiation activates Akt and Nrf2 in the kidney of diabetic mice: a potential mechanism to prevent diabetic nephropathy. Oxid Med Cell Longev 2012:291087. CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Shao M, Lu X, Cong W, Xing X, Tan Y, Li Y, Li X, Jin L, Wang X, Dong J, Jin S, Zhang C, Cai L (2014) Multiple low-dose radiation prevents type 2 diabetes-induced renal damage through attenuation of dyslipidemia and insulin resistance and subsequent renal inflammation and oxidative stress. PLoS One 9(3):e92574. CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Zhang C, Xing X, Zhang F, Shao M, Jin S, Yang H, Wang G, Cui J, Cai L, Li W, Lu X (2014) Low-dose radiation induces renal SOD1 expression and activity in type 1 diabetic mice. Int J Radiat Biol 90(3):224–230. CrossRefPubMedGoogle Scholar
  50. 50.
    Komatsu M, Kurokawa H, Waguri S, Taguchi K, Kobayashi A, Ichimura Y, Sou YS, Ueno I, Sakamoto A, Tong KI, Kim M, Nishito Y, Iemura S, Natsume T, Ueno T, Kominami E, Motohashi H, Tanaka K, Yamamoto M (2010) The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nat Cell Biol 12(3):213–223. CrossRefPubMedGoogle Scholar
  51. 51.
    Taguchi K, Fujikawa N, Komatsu M, Ishii T, Unno M, Akaike T, Motohashi H, Yamamoto M (2012) Keap1 degradation by autophagy for the maintenance of redox homeostasis. Proc Natl Acad Sci USA 109(34):13561–13566. CrossRefPubMedGoogle Scholar
  52. 52.
    DeNicola GM, Karreth FA, Humpton TJ, Gopinathan A, Wei C, Frese K, Mangal D, Yu KH, Yeo CJ, Calhoun ES, Scrimieri F, Winter JM, Hruban RH, Iacobuzio-Donahue C, Kern SE, Blair IA, Tuveson DA (2011) Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis. Nature 475(7354):106–109. CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Wang XJ, Sun Z, Villeneuve NF, Zhang S, Zhao F, Li Y, Chen W, Yi X, Zheng W, Wondrak GT, Wong PK, Zhang DD (2008) Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2. Carcinogenesis 29(6):1235–1243. CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Chen N, Wu L, Yuan H, Wang J (2015) ROS/autophagy/Nrf2 pathway mediated low-dose radiation induced radio-resistance in human lung adenocarcinoma A549 cell. Int J Biol Sci 11(7):833–844. CrossRefPubMedPubMedCentralGoogle Scholar
  55. 55.
    Bryan HK, Olayanju A, Goldring CE, Park BK (2013) The Nrf2 cell defence pathway: Keap1-dependent and -independent mechanisms of regulation. Biochem Pharmacol 85(6):705–717. CrossRefPubMedGoogle Scholar
  56. 56.
    Ayers D, Baron B, Hunter T (2015) miRNA influences in NRF2 pathway interactions within cancer models. J Nucleic Acids 2015:143636. CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Wagner AE, Boesch-Saadatmandi C, Dose J, Schultheiss G, Rimbach G (2012) Anti-inflammatory potential of allyl-isothiocyanate–role of Nrf2, NF-(kappa) B and microRNA-155. J Cell Mol Med 16(4):836–843. CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Miao W, Hu L, Scrivens PJ, Batist G (2005) Transcriptional regulation of NF-E2 p45-related factor (NRF2) expression by the aryl hydrocarbon receptor-xenobiotic response element signaling pathway: direct cross-talk between phase I and II drug-metabolizing enzymes. J Biol Chem 280(21):20340–20348. CrossRefPubMedGoogle Scholar
  59. 59.
    Joo MS, Lee CG, Koo JH, Kim SG (2013) miR-125b transcriptionally increased by Nrf2 inhibits AhR repressor, which protects kidney from cisplatin-induced injury. Cell Death Dis 4:e899. CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Hayden MS, Ghosh S (2011) NF-kappaB in immunobiology. Cell Res 21(2):223–244. CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Prasad AV, Mohan N, Chandrasekar B, Meltz ML (1994) Activation of nuclear factor kappa B in human lymphoblastoid cells by low-dose ionizing radiation. Radiat Res 138(3):367–372CrossRefPubMedGoogle Scholar
  62. 62.
    Rodel F, Hantschel M, Hildebrandt G, Schultze-Mosgau S, Rodel C, Herrmann M, Sauer R, Voll RE (2004) Dose-dependent biphasic induction and transcriptional activity of nuclear factor kappa B (NF-kappaB) in EA.hy.926 endothelial cells after low-dose X-irradiation. Int J Radiat Biol 80(2):115–123. CrossRefPubMedGoogle Scholar
  63. 63.
    Rodel F, Frey B, Capalbo G, Gaipl U, Keilholz L, Voll R, Hildebrandt G, Rodel C (2010) Discontinuous induction of X-linked inhibitor of apoptosis in EA.hy.926 endothelial cells is linked to NF-kappaB activation and mediates the anti-inflammatory properties of low-dose ionising-radiation. Radiother Oncol 97(2):346–351. CrossRefPubMedGoogle Scholar
  64. 64.
    Lodermann B, Wunderlich R, Frey S, Schorn C, Stangl S, Rodel F, Keilholz L, Fietkau R, Gaipl US, Frey B (2012) Low dose ionising radiation leads to a NF-kappaB dependent decreased secretion of active IL-1beta by activated macrophages with a discontinuous dose-dependency. Int J Radiat Biol 88(10):727–734. CrossRefPubMedGoogle Scholar
  65. 65.
    Kim CS, Kim JK, Nam SY, Yang KH, Jeong M, Kim HS, Jin YW, Kim J (2007) Low-dose radiation stimulates the proliferation of normal human lung fibroblasts via a transient activation of Raf and Akt. Mol Cells 24(3):424–430PubMedGoogle Scholar
  66. 66.
    Murley JS, Kataoka Y, Weydert CJ, Oberley LW, Grdina DJ (2006) Delayed radioprotection by nuclear transcription factor kappaB-mediated induction of manganese superoxide dismutase in human microvascular endothelial cells after exposure to the free radical scavenger WR1065. Free Radic Biol Med 40(6):1004–1016. CrossRefPubMedGoogle Scholar
  67. 67.
    Park HS, Seong KM, Kim JY, Kim CS, Yang KH, Jin YW, Nam SY (2013) Chronic low-dose radiation inhibits the cells death by cytotoxic high-dose radiation increasing the level of AKT and acinus proteins via NF-kappaB activation. Int J Radiat Biol 89(5):371–377. CrossRefPubMedGoogle Scholar
  68. 68.
    Murley JS, Baker KL, Miller RC, Darga TE, Weichselbaum RR, Grdina DJ (2011) SOD2-mediated adaptive responses induced by low-dose ionizing radiation via TNF signaling and amifostine. Free Radic Biol Med 51(10):1918–1925. CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Lake D, Correa SA, Muller J (2016) Negative feedback regulation of the ERK1/2 MAPK pathway. Cell Mol Life Sci 73(23):4397–4413. CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    McKay MM, Morrison DK (2007) Integrating signals from RTKs to ERK/MAPK. Oncogene 26(22):3113–3121. CrossRefPubMedGoogle Scholar
  71. 71.
    Dent P, Yacoub A, Fisher PB, Hagan MP, Grant S (2003) MAPK pathways in radiation responses. Oncogene 22(37):5885–5896. CrossRefPubMedGoogle Scholar
  72. 72.
    Kim CS, Kim JM, Nam SY, Yang KH, Jeong M, Kim HS, Lim YK, Jin YW, Kim J (2007) Low-dose of ionizing radiation enhances cell proliferation via transient ERK1/2 and p38 activation in normal human lung fibroblasts. J Radiat Res 48(5):407–415CrossRefPubMedGoogle Scholar
  73. 73.
    Park HS, You GE, Yang KH, Kim JY, An S, Song JY, Lee SJ, Lim YK, Nam SY (2015) Role of AKT and ERK pathways in controlling sensitivity to ionizing radiation and adaptive response induced by low-dose radiation in human immune cells. Eur J Cell Biol 94(12):653–660. CrossRefPubMedGoogle Scholar
  74. 74.
    Yu H, Liu N, Wang H, Shang Q, Jiang P, Zhang Y (2013) Different responses of tumor and normal cells to low-dose radiation. Contemp Oncol (Pozn) 17(4):356–362. CrossRefGoogle Scholar
  75. 75.
    Asur R, Balasubramaniam M, Marples B, Thomas RA, Tucker JD (2010) Involvement of MAPK proteins in bystander effects induced by chemicals and ionizing radiation. Mutat Res 686(1–2):15–29. CrossRefPubMedGoogle Scholar
  76. 76.
    Jiang T, Harder B, Rojo de la Vega M, Wong PK, Chapman E, Zhang DD (2015) p62 links autophagy and Nrf2 signaling. Free Radic Biol Med 88(Pt B):199–204. CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Cullinan SB, Zhang D, Hannink M, Arvisais E, Kaufman RJ, Diehl JA (2003) Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival. Mol Cell Biol 23(20):7198–7209CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Woo CW, Cui D, Arellano J, Dorweiler B, Harding H, Fitzgerald KA, Ron D, Tabas I (2009) Adaptive suppression of the ATF4-CHOP branch of the unfolded protein response by toll-like receptor signalling. Nat Cell Biol 11(12):1473–1480. CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Zinszner H, Kuroda M, Wang X, Batchvarova N, Lightfoot RT, Remotti H, Stevens JL, Ron D (1998) CHOP is implicated in programmed cell death in response to impaired function of the endoplasmic reticulum. Genes Dev 12(7):982–995CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Li N, Hao M, Phalen RF, Hinds WC, Nel AE (2003) Particulate air pollutants and asthma. A paradigm for the role of oxidative stress in PM-induced adverse health effects. Clin Immunol 109(3):250–265CrossRefPubMedGoogle Scholar
  81. 81.
    Kroemer G, Marino G, Levine B (2010) Autophagy and the integrated stress response. Mol Cell 40(2):280–293. CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Zhang Q, Kang R, Zeh HJ 3rd, Lotze MT, Tang D (2013) DAMPs and autophagy: cellular adaptation to injury and unscheduled cell death. Autophagy 9(4):451–458. CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Scarlatti F, Granata R, Meijer AJ, Codogno P (2009) Does autophagy have a license to kill mammalian cells? Cell Death Differ 16(1):12–20. CrossRefPubMedGoogle Scholar
  84. 84.
    Fougeray S, Pallet N (2015) Mechanisms and biological functions of autophagy in diseased and ageing kidneys. Nat Rev Nephrol 11(1):34–45. CrossRefPubMedGoogle Scholar
  85. 85.
    Jiang M, Liu K, Luo J, Dong Z (2010) Autophagy is a renoprotective mechanism during in vitro hypoxia and in vivo ischemia-reperfusion injury. Am J Pathol 176(3):1181–1192. CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Vion AC, Kheloufi M, Hammoutene A, Poisson J, Lasselin J, Devue C, Pic I, Dupont N, Busse J, Stark K, Lafaurie-Janvore J, Barakat AI, Loyer X, Souyri M, Viollet B, Julia P, Tedgui A, Codogno P, Boulanger CM, Rautou PE (2017) Autophagy is required for endothelial cell alignment and atheroprotection under physiological blood flow. Proc Natl Acad Sci USA 114(41):E8675–E8684. CrossRefPubMedGoogle Scholar
  87. 87.
    Paglin S, Hollister T, Delohery T, Hackett N, McMahill M, Sphicas E, Domingo D, Yahalom J (2001) A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles. Cancer Res 61(2):439–444PubMedGoogle Scholar
  88. 88.
    Paglin S, Lee NY, Nakar C, Fitzgerald M, Plotkin J, Deuel B, Hackett N, McMahill M, Sphicas E, Lampen N, Yahalom J (2005) Rapamycin-sensitive pathway regulates mitochondrial membrane potential, autophagy, and survival in irradiated MCF-7 cells. Cancer Res 65(23):11061–11070. CrossRefPubMedGoogle Scholar
  89. 89.
    Paglin S, Yahalom J (2006) Pathways that regulate autophagy and their role in mediating tumor response to treatment. Autophagy 2(4):291–293CrossRefPubMedGoogle Scholar
  90. 90.
    Zois CE, Koukourakis MI (2009) Radiation-induced autophagy in normal and cancer cells: towards novel cytoprotection and radio-sensitization policies? Autophagy 5(4):442–450CrossRefPubMedGoogle Scholar
  91. 91.
    Kim H, Bernard ME, Flickinger J, Epperly MW, Wang H, Dixon TM, Shields D, Houghton F, Zhang X, Greenberger JS (2011) The autophagy-inducing drug carbamazepine is a radiation protector and mitigator. Int J Radiat Biol 87(10):1052–1060. CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Chargui A, Zekri S, Jacquillet G, Rubera I, Ilie M, Belaid A, Duranton C, Tauc M, Hofman P, Poujeol P, El May MV, Mograbi B (2011) Cadmium-induced autophagy in rat kidney: an early biomarker of subtoxic exposure. Toxicol Sci 121(1):31–42. CrossRefPubMedGoogle Scholar
  93. 93.
    Clevers H, Nusse R (2012) Wnt/beta-catenin signaling and disease. Cell 149(6):1192–1205. CrossRefPubMedGoogle Scholar
  94. 94.
    van Amerongen R, Nusse R (2009) Towards an integrated view of Wnt signaling in development. Development 136(19):3205–3214. CrossRefPubMedGoogle Scholar
  95. 95.
    Staal FJ, Luis TC, Tiemessen MM (2008) WNT signalling in the immune system: WNT is spreading its wings. Nat Rev Immunol 8(8):581–593. CrossRefPubMedGoogle Scholar
  96. 96.
    Zhang RF, Wang Q, Zhang AA, Xu JG, Zhai LD, Yang XM, Liu XT (2018) Low-level laser irradiation promotes the differentiation of bone marrow stromal cells into osteoblasts through the APN/Wnt/beta-catenin pathway. Eur Rev Med Pharmacol Sci 22(9):2860–2868. CrossRefPubMedGoogle Scholar
  97. 97.
    Alexandrou AT, Li JJ (2014) Cell cycle regulators guide mitochondrial activity in radiation-induced adaptive response. Antioxid Redox Signal 20(9):1463–1480. CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Maes OC, An J, Sarojini H, Wu H, Wang E (2008) Changes in MicroRNA expression patterns in human fibroblasts after low-LET radiation. J Cell Biochem 105(3):824–834. CrossRefPubMedGoogle Scholar
  99. 99.
    Kern P, Keilholz L, Forster C, Seegenschmiedt MH, Sauer R, Herrmann M (1999) In vitro apoptosis in peripheral blood mononuclear cells induced by low-dose radiotherapy displays a discontinuous dose-dependence. Int J Radiat Biol 75(8):995–1003CrossRefPubMedGoogle Scholar
  100. 100.
    Kern PM, Keilholz L, Forster C, Stach C, Beyer TD, Gaipl US, Kalden JR, Hallmann R, Herrmann M (2000) UVB-irradiated T-cells undergoing apoptosis lose L-selectin by metalloprotese-mediated shedding. Int J Radiat Biol 76(9):1265–1271CrossRefPubMedGoogle Scholar
  101. 101.
    Gaipl US, Meister S, Lodermann B, Rodel F, Fietkau R, Herrmann M, Kern PM, Frey B (2009) Activation-induced cell death and total Akt content of granulocytes show a biphasic course after low-dose radiation. Autoimmunity 42(4):340–342CrossRefPubMedGoogle Scholar
  102. 102.
    Candas D, Fan M, Nantajit D, Vaughan AT, Murley JS, Woloschak GE, Grdina DJ, Li JJ (2013) CyclinB1/Cdk1 phosphorylates mitochondrial antioxidant MnSOD in cell adaptive response to radiation stress. J Mol Cell Biol 5(3):166–175. CrossRefPubMedGoogle Scholar
  103. 103.
    Amundson SA, Lee RA, Koch-Paiz CA, Bittner ML, Meltzer P, Trent JM, Fornace AJ Jr (2003) Differential responses of stress genes to low dose-rate gamma irradiation. Mol Cancer Res 1(6):445–452PubMedGoogle Scholar
  104. 104.
    Azimian H, Bahreyni-Toossi MT, Rezaei AR, Rafatpanah H, Hamzehloei T, Fardid R (2015) Up-regulation of Bcl-2 expression in cultured human lymphocytes after exposure to low doses of gamma radiation. J Med Phys 40(1):38–44. CrossRefPubMedPubMedCentralGoogle Scholar
  105. 105.
    Wei LC, Ding YX, Liu YH, Duan L, Bai Y, Shi M, Chen LW (2012) Low-dose radiation stimulates Wnt/beta-catenin signaling, neural stem cell proliferation and neurogenesis of the mouse hippocampus in vitro and in vivo. Curr Alzheimer Res 9(3):278–289CrossRefPubMedGoogle Scholar
  106. 106.
    Zhao L, Ackerman SL (2006) Endoplasmic reticulum stress in health and disease. Curr Opin Cell Biol 18(4):444–452. CrossRefPubMedGoogle Scholar
  107. 107.
    Pallet N, Fougeray S, Beaune P, Legendre C, Thervet E, Anglicheau D (2009) Endoplasmic reticulum stress: an unrecognized actor in solid organ transplantation. Transplantation 88(5):605–613. CrossRefPubMedGoogle Scholar
  108. 108.
    Kaufman RJ (2002) Orchestrating the unfolded protein response in health and disease. J Clin Invest 110(10):1389–1398. CrossRefPubMedPubMedCentralGoogle Scholar
  109. 109.
    Kitamura M (2008) Endoplasmic reticulum stress in the kidney. Clin Exp Nephrol 12(5):317–325. CrossRefPubMedGoogle Scholar
  110. 110.
    La Rovere RM, Roest G, Bultynck G, Parys JB (2016) Intracellular Ca(2+) signaling and Ca(2+) microdomains in the control of cell survival, apoptosis and autophagy. Cell Calcium 60(2):74–87. CrossRefPubMedGoogle Scholar
  111. 111.
    Shinkai Y, Kaji T (2012) Cellular defense mechanisms against lead toxicity in the vascular system. Biol Pharm Bull 35(11):1885–1891CrossRefPubMedGoogle Scholar
  112. 112.
    Peyrou M, Cribb AE (2007) Effect of endoplasmic reticulum stress preconditioning on cytotoxicity of clinically relevant nephrotoxins in renal cell lines. Toxicol In Vitro 21(5):878–886. CrossRefPubMedGoogle Scholar
  113. 113.
    Qian Y, Falahatpisheh MH, Zheng Y, Ramos KS, Tiffany-Castiglioni E (2001) Induction of 78 kD glucose-regulated protein (GRP78) expression and redox-regulated transcription factor activity by lead and mercury in C6 rat glioma cells. Neurotox Res 3(6):581–589CrossRefPubMedGoogle Scholar
  114. 114.
    Chandrika BB, Yang C, Ou Y, Feng X, Muhoza D, Holmes AF, Theus S, Deshmukh S, Haun RS, Kaushal GP (2015) Endoplasmic reticulum stress-induced autophagy provides cytoprotection from chemical hypoxia and oxidant injury and ameliorates renal ischemia-reperfusion injury. PLoS One 10(10):e0140025. CrossRefPubMedPubMedCentralGoogle Scholar
  115. 115.
    Qian Y, Harris ED, Zheng Y, Tiffany-Castiglioni E (2000) Lead targets GRP78, a molecular chaperone, in C6 rat glioma cells. Toxicol Appl Pharmacol 163(3):260–266. CrossRefPubMedGoogle Scholar
  116. 116.
    Nagasawa H, Little JB (1992) Induction of sister chromatid exchanges by extremely low doses of alpha-particles. Cancer Res 52(22):6394–6396PubMedGoogle Scholar
  117. 117.
    Hamada N, Matsumoto H, Hara T, Kobayashi Y (2007) Intercellular and intracellular signaling pathways mediating ionizing radiation-induced bystander effects. J Radiat Res 48(2):87–95CrossRefPubMedGoogle Scholar
  118. 118.
    Mothersill C, Seymour C (2004) Radiation-induced bystander effects and adaptive responses–the Yin and Yang of low dose radiobiology? Mutat Res 568(1):121–128. CrossRefPubMedGoogle Scholar
  119. 119.
    Iyer R, Lehnert BE (2002) Low dose, low-LET ionizing radiation-induced radioadaptation and associated early responses in unirradiated cells. Mutat Res 503(1–2):1–9CrossRefPubMedGoogle Scholar
  120. 120.
    Nobler MP (1969) The abscopal effect in malignant lymphoma and its relationship to lymphocyte circulation. Radiology 93(2):410–412. CrossRefPubMedGoogle Scholar
  121. 121.
    Xue LY, Butler NJ, Makrigiorgos GM, Adelstein SJ, Kassis AI (2002) Bystander effect produced by radiolabeled tumor cells in vivo. Proc Natl Acad Sci USA 99(21):13765–13770. CrossRefPubMedGoogle Scholar
  122. 122.
    Kassis AI (2004) In vivo validation of the bystander effect. Hum Exp Toxicol 23(2):71–73CrossRefPubMedGoogle Scholar
  123. 123.
    Morgan WF (2003) Non-targeted and delayed effects of exposure to ionizing radiation: II. Radiation-induced genomic instability and bystander effects in vivo, clastogenic factors and transgenerational effects. Radiat Res 159(5):581–596CrossRefPubMedGoogle Scholar
  124. 124.
    Azzam EI, de Toledo SM, Gooding T, Little JB (1998) Intercellular communication is involved in the bystander regulation of gene expression in human cells exposed to very low fluences of alpha particles. Radiat Res 150(5):497–504CrossRefPubMedGoogle Scholar
  125. 125.
    Azzam EI, de Toledo SM, Little JB (2001) Direct evidence for the participation of gap junction-mediated intercellular communication in the transmission of damage signals from alpha-particle irradiated to nonirradiated cells. Proc Natl Acad Sci USA 98(2):473–478. CrossRefPubMedGoogle Scholar
  126. 126.
    Iyer R, Lehnert BE, Svensson R (2000) Factors underlying the cell growth-related bystander responses to alpha particles. Cancer Res 60(5):1290–1298PubMedGoogle Scholar
  127. 127.
    Mothersill C, Seymour CB (1998) Cell-cell contact during gamma irradiation is not required to induce a bystander effect in normal human keratinocytes: evidence for release during irradiation of a signal controlling survival into the medium. Radiat Res 149(3):256–262CrossRefPubMedGoogle Scholar
  128. 128.
    Portess DI, Bauer G, Hill MA, O’Neill P (2007) Low-dose irradiation of nontransformed cells stimulates the selective removal of precancerous cells via intercellular induction of apoptosis. Cancer Res 67(3):1246–1253. CrossRefPubMedGoogle Scholar
  129. 129.
    Han W, Zhu L, Jiang E, Wang J, Chen S, Bao L, Zhao Y, Xu A, Yu Z, Wu L (2007) Elevated sodium chloride concentrations enhance the bystander effects induced by low dose alpha-particle irradiation. Mutat Res 624(1–2):124–131. CrossRefPubMedGoogle Scholar
  130. 130.
    Ma S, Liu X, Jiao B, Yang Y (2010) Low-dose radiation-induced responses: focusing on epigenetic regulation. Int J Radiat Biol 86(7):517–528. CrossRefPubMedGoogle Scholar
  131. 131.
    Raiche J, Rodriguez-Juarez R, Pogribny I, Kovalchuk O (2004) Sex- and tissue-specific expression of maintenance and de novo DNA methyltransferases upon low dose X-irradiation in mice. Biochem Biophys Res Commun 325(1):39–47. CrossRefPubMedGoogle Scholar
  132. 132.
    Pogribny I, Raiche J, Slovack M, Kovalchuk O (2004) Dose-dependence, sex- and tissue-specificity, and persistence of radiation-induced genomic DNA methylation changes. Biochem Biophys Res Commun 320(4):1253–1261. CrossRefPubMedGoogle Scholar
  133. 133.
    Dickey JS, Zemp FJ, Martin OA, Kovalchuk O (2011) The role of miRNA in the direct and indirect effects of ionizing radiation. Radiat Environ Biophys 50(4):491–499. CrossRefPubMedGoogle Scholar
  134. 134.
    Xu S, Ding N, Pei H, Hu W, Wei W, Zhang X, Zhou G, Wang J (2014) MiR-21 is involved in radiation-induced bystander effects. RNA Biol 11(9):1161–1170. CrossRefPubMedPubMedCentralGoogle Scholar
  135. 135.
    Xu S, Wang J, Ding N, Hu W, Zhang X, Wang B, Hua J, Wei W, Zhu Q (2015) Exosome-mediated microRNA transfer plays a role in radiation-induced bystander effect. RNA Biol 12(12):1355–1363. CrossRefPubMedPubMedCentralGoogle Scholar
  136. 136.
    Asur RS, Thomas RA, Tucker JD (2009) Chemical induction of the bystander effect in normal human lymphoblastoid cells. Mutat Res 676(1–2):11–16. CrossRefPubMedGoogle Scholar
  137. 137.
    Alexandre J, Hu Y, Lu W, Pelicano H, Huang P (2007) Novel action of paclitaxel against cancer cells: bystander effect mediated by reactive oxygen species. Cancer Res 67(8):3512–3517. CrossRefPubMedGoogle Scholar
  138. 138.
    Demidem A, Morvan D, Madelmont JC (2006) Bystander effects are induced by CENU treatment and associated with altered protein secretory activity of treated tumor cells: a relay for chemotherapy? Int J Cancer 119(5):992–1004. CrossRefPubMedGoogle Scholar
  139. 139.
    Rugo RE, Almeida KH, Hendricks CA, Jonnalagadda VS, Engelward BP (2005) A single acute exposure to a chemotherapeutic agent induces hyper-recombination in distantly descendant cells and in their neighbors. Oncogene 24(32):5016–5025. CrossRefPubMedGoogle Scholar
  140. 140.
    Klaassen CD, Liu J (1998) Metallothionein transgenic and knock-out mouse models in the study of cadmium toxicity. J Toxicol Sci 23(Suppl 2):97–102CrossRefPubMedGoogle Scholar
  141. 141.
    Myers JP, Zoeller RT, vom Saal FS (2009) A clash of old and new scientific concepts in toxicity, with important implications for public health. Environ Health Perspect 117(11):1652–1655. CrossRefPubMedPubMedCentralGoogle Scholar
  142. 142.
    Nair AR, Lee WK, Smeets K, Swennen Q, Sanchez A, Thevenod F, Cuypers A (2015) Glutathione and mitochondria determine acute defense responses and adaptive processes in cadmium-induced oxidative stress and toxicity of the kidney. Arch Toxicol 89(12):2273–2289. CrossRefPubMedGoogle Scholar
  143. 143.
    Poisson C, Stefani J, Manens L, Delissen O, Suhard D, Tessier C, Dublineau I, Gueguen Y (2014) Chronic uranium exposure dose-dependently induces glutathione in rats without any nephrotoxicity. Free Radic Res 48(10):1218–1231. CrossRefPubMedGoogle Scholar
  144. 144.
    Gueguen Y, Rouas C, Monin A, Manens L, Stefani J, Delissen O, Grison S, Dublineau I (2014) Molecular, cellular, and tissue impact of depleted uranium on xenobiotic-metabolizing enzymes. Arch Toxicol 88(2):227–239. CrossRefPubMedGoogle Scholar
  145. 145.
    Korashy HM, El-Kadi AO (2006) Transcriptional regulation of the NAD(P)H:quinone oxidoreductase 1 and glutathione S-transferase ya genes by mercury, lead, and copper. Drug Metab Dispos 34(1):152–165CrossRefPubMedGoogle Scholar
  146. 146.
    Kataoka T (2013) Study of antioxidative effects and anti-inflammatory effects in mice due to low-dose X-irradiation or radon inhalation. J Radiat Res 54(4):587–596. CrossRefPubMedPubMedCentralGoogle Scholar
  147. 147.
    Kojima S, Nakayama K, Ishida H (2004) Low dose gamma-rays activate immune functions via induction of glutathione and delay tumor growth. J Radiat Res 45(1):33–39CrossRefPubMedGoogle Scholar
  148. 148.
    Nomura T, Yamaoka K (1999) Low-dose gamma-ray irradiation reduces oxidative damage induced by CCl4 in mouse liver. Free Radic Biol Med 27(11–12):1324–1333CrossRefPubMedGoogle Scholar
  149. 149.
    Bravard A, Luccioni C, Moustacchi E, Rigaud O (1999) Contribution of antioxidant enzymes to the adaptive response to ionizing radiation of human lymphoblasts. Int J Radiat Biol 75(5):639–645CrossRefPubMedGoogle Scholar
  150. 150.
    Cui J, Yang G, Pan Z, Zhao Y, Liang X, Li W, Cai L (2017) Hormetic response to low-dose radiation: focus on the immune system and its clinical implications. Int J Mol Sci 18(2):280. CrossRefPubMedCentralGoogle Scholar
  151. 151.
    Rodel F, Frey B, Gaipl U, Keilholz L, Fournier C, Manda K, Schollnberger H, Hildebrandt G, Rodel C (2012) Modulation of inflammatory immune reactions by low-dose ionizing radiation: molecular mechanisms and clinical application. Curr Med Chem 19(12):1741–1750CrossRefPubMedGoogle Scholar
  152. 152.
    Scott BR (2014) Radiation-hormesis phenotypes, the related mechanisms and implications for disease prevention and therapy. J Cell Commun Signal 8(4):341–352. CrossRefPubMedPubMedCentralGoogle Scholar
  153. 153.
    Ina Y, Sakai K (2005) Activation of immunological network by chronic low-dose-rate irradiation in wild-type mouse strains: analysis of immune cell populations and surface molecules. Int J Radiat Biol 81(10):721–729. CrossRefPubMedGoogle Scholar
  154. 154.
    Luckey TD (1982) Physiological benefits from low levels of ionizing radiation. Health Phys 43(6):771–789CrossRefPubMedGoogle Scholar
  155. 155.
    Bogdandi EN, Balogh A, Felgyinszki N, Szatmari T, Persa E, Hildebrandt G, Safrany G, Lumniczky K (2010) Effects of low-dose radiation on the immune system of mice after total-body irradiation. Radiat Res 174(4):480–489. CrossRefPubMedGoogle Scholar
  156. 156.
    Klug F, Prakash H, Huber PE, Seibel T, Bender N, Halama N, Pfirschke C, Voss RH, Timke C, Umansky L, Klapproth K, Schakel K, Garbi N, Jager D, Weitz J, Schmitz-Winnenthal H, Hammerling GJ, Beckhove P (2013) Low-dose irradiation programs macrophage differentiation to an iNOS(+)/M1 phenotype that orchestrates effective T cell immunotherapy. Cancer Cell 24(5):589–602. CrossRefPubMedGoogle Scholar
  157. 157.
    Wunderlich R, Ernst A, Rodel F, Fietkau R, Ott O, Lauber K, Frey B, Gaipl US (2015) Low and moderate doses of ionizing radiation up to 2 Gy modulate transmigration and chemotaxis of activated macrophages, provoke an anti-inflammatory cytokine milieu, but do not impact upon viability and phagocytic function. Clin Exp Immunol 179(1):50–61. CrossRefPubMedGoogle Scholar
  158. 158.
    Vieira Dias J, Gloaguen C, Kereselidze D, Manens L, Tack K, Ebrahimian TG (2018) Gamma low-dose-rate ionizing radiation stimulates adaptive functional and molecular response in human aortic endothelial cells in a threshold-, dose-, and dose rate-dependent manner. Dose Response 16(1):1559325818755238. CrossRefPubMedPubMedCentralGoogle Scholar
  159. 159.
    Budras KD, Hartung K, Munzer BM (1986) Light and electron microscopy studies of the effect of roentgen irradiation on the synovial membrane of the inflamed knee joint. Berl Munch Tierarztl Wochenschr 99(5):148–152PubMedGoogle Scholar
  160. 160.
    Pandey R, Shankar BS, Sharma D, Sainis KB (2005) Low dose radiation induced immunomodulation: effect on macrophages and CD8+ T cells. Int J Radiat Biol 81(11):801–812. CrossRefPubMedGoogle Scholar
  161. 161.
    Trott KR, Parker R, Seed MP (1995) The effect of x-rays on experimental arthritis in the rat. Strahlenther Onkol 171(9):534–538PubMedGoogle Scholar
  162. 162.
    Hildebrandt G, Radlingmayr A, Rosenthal S, Rothe R, Jahns J, Hindemith M, Rodel F, Kamprad F (2003) Low-dose radiotherapy (LD-RT) and the modulation of iNOS expression in adjuvant-induced arthritis in rats. Int J Radiat Biol 79(12):993–1001. CrossRefPubMedGoogle Scholar
  163. 163.
    Schaue D, Jahns J, Hildebrandt G, Trott KR (2005) Radiation treatment of acute inflammation in mice. Int J Radiat Biol 81(9):657–667. CrossRefPubMedGoogle Scholar
  164. 164.
    Nakatsukasa H, Tsukimoto M, Ohshima Y, Tago F, Masada A, Kojima S (2008) Suppressing effect of low-dose gamma-ray irradiation on collagen-induced arthritis. J Radiat Res 49(4):381–389CrossRefPubMedGoogle Scholar
  165. 165.
    Zaiss MM, Frey B, Hess A, Zwerina J, Luther J, Nimmerjahn F, Engelke K, Kollias G, Hunig T, Schett G, David JP (2010) Regulatory T cells protect from local and systemic bone destruction in arthritis. J Immunol 184(12):7238–7246. CrossRefPubMedGoogle Scholar
  166. 166.
    Frey B, Gaipl US, Sarter K, Zaiss MM, Stillkrieg W, Rodel F, Schett G, Herrmann M, Fietkau R, Keilholz L (2009) Whole body low dose irradiation improves the course of beginning polyarthritis in human TNF-transgenic mice. Autoimmunity 42(4):346–348CrossRefPubMedGoogle Scholar
  167. 167.
    Aunapuu M, Pechter U, Gerskevits E, Marjamagi MM, Suuroja S, Arend A, Kolts I, Kuhnel W, Ots M (2004) Low-dose radiation modifies the progression of chronic renal failure. Ann Anat 186(3):277–282. CrossRefPubMedGoogle Scholar
  168. 168.
    Pathak CM, Avti PK, Kumar S, Khanduja KL, Sharma SC (2007) Whole body exposure to low-dose gamma radiation promotes kidney antioxidant status in Balb/c mice. J Radiat Res 48(2):113–120CrossRefPubMedGoogle Scholar
  169. 169.
    Ruiz S, Pergola PE, Zager RA, Vaziri ND (2013) Targeting the transcription factor Nrf2 to ameliorate oxidative stress and inflammation in chronic kidney disease. Kidney Int 83(6):1029–1041. CrossRefPubMedPubMedCentralGoogle Scholar
  170. 170.
    Yoh K, Itoh K, Enomoto A, Hirayama A, Yamaguchi N, Kobayashi M, Morito N, Koyama A, Yamamoto M, Takahashi S (2001) Nrf2-deficient female mice develop lupus-like autoimmune nephritis. Kidney Int 60(4):1343–1353. CrossRefPubMedGoogle Scholar
  171. 171.
    Yoh K, Hirayama A, Ishizaki K, Yamada A, Takeuchi M, Yamagishi S, Morito N, Nakano T, Ojima M, Shimohata H, Itoh K, Takahashi S, Yamamoto M (2008) Hyperglycemia induces oxidative and nitrosative stress and increases renal functional impairment in Nrf2-deficient mice. Genes Cells 13(11):1159–1170. CrossRefPubMedGoogle Scholar
  172. 172.
    Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, Weiner HL, Kuchroo VK (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441(7090):235–238. CrossRefPubMedPubMedCentralGoogle Scholar
  173. 173.
    Farooque A, Mathur R, Verma A, Kaul V, Bhatt AN, Adhikari JS, Afrin F, Singh S, Dwarakanath BS (2011) Low-dose radiation therapy of cancer: role of immune enhancement. Expert Rev Anticancer Ther 11(5):791–802. CrossRefPubMedGoogle Scholar
  174. 174.
    Weng L, Williams RO, Vieira PL, Screaton G, Feldmann M, Dazzi F (2010) The therapeutic activity of low-dose irradiation on experimental arthritis depends on the induction of endogenous regulatory T cell activity. Ann Rheum Dis 69(8):1519–1526. CrossRefPubMedGoogle Scholar
  175. 175.
    Ebrahimian T, Le Gallic C, Stefani J, Dublineau I, Yentrapalli R, Harms-Ringdahl M, Haghdoost S (2015) Chronic gamma-irradiation induces a dose-rate-dependent pro-inflammatory response and associated loss of function in human umbilical vein endothelial cells. Radiat Res 183(4):447–454. CrossRefPubMedGoogle Scholar
  176. 176.
    Hoving S, Heeneman S, Gijbels MJ, te Poele JA, Russell NS, Daemen MJ, Stewart FA (2008) Single-dose and fractionated irradiation promote initiation and progression of atherosclerosis and induce an inflammatory plaque phenotype in ApoE(−/−) mice. Int J Radiat Oncol Biol Phys 71(3):848–857. CrossRefPubMedGoogle Scholar
  177. 177.
    AGIR (2010) Report of the independent Advisory Group on Ionising Radiation—Circulatory Disease Risk. Documents of the Health Protection Agency. Radiation, Chemical and Environmental Hazards: Chilton, Doc HPA, RCE-16, 1-116Google Scholar
  178. 178.
    Le Gallic C, Phalente Y, Manens L, Dublineau I, Benderitter M, Gueguen Y, Lehoux S, Ebrahimian TG (2015) Chronic internal exposure to low dose 137Cs induces positive impact on the stability of atherosclerotic plaques by reducing inflammation in ApoE−/− mice. PLoS One 10(6):e0128539. CrossRefPubMedPubMedCentralGoogle Scholar
  179. 179.
    Mitchel RE, Hasu M, Bugden M, Wyatt H, Little MP, Gola A, Hildebrandt G, Priest ND, Whitman SC (2011) Low-dose radiation exposure and atherosclerosis in ApoE(−)/(−) mice. Radiat Res 175(5):665–676. CrossRefPubMedPubMedCentralGoogle Scholar
  180. 180.
    Zhang C, Jin S, Guo W, Li C, Li X, Rane MJ, Wang G, Cai L (2011) Attenuation of diabetes-induced cardiac inflammation and pathological remodeling by low-dose radiation. Radiat Res 175(3):307–321. CrossRefPubMedGoogle Scholar
  181. 181.
    Chen W, Xu X, Bai L, Padilla MT, Gott KM, Leng S, Tellez CS, Wilder JA, Belinsky SA, Scott BR, Lin Y (2012) Low-dose gamma-irradiation inhibits IL-6 secretion from human lung fibroblasts that promotes bronchial epithelial cell transformation by cigarette-smoke carcinogen. Carcinogenesis 33(7):1368–1374. CrossRefPubMedGoogle Scholar
  182. 182.
    Bruce VR, Belinsky SA, Gott K, Liu Y, March T, Scott B, Wilder J (2012) Low-dose gamma-radiation inhibits benzo[a]pyrene-induced lung adenoma development in A/J mice. Dose Response 10(4):516–526. CrossRefPubMedPubMedCentralGoogle Scholar
  183. 183.
    Calabrese EJ, Baldwin LA, Kostecki PT, Potter TL (1997) A toxicologically based weight-of-evidence methodology for the relative ranking of chemicals of endocrine disruption potential. Regul Toxicol Pharmacol 26(1 Pt 1):36–40. CrossRefPubMedGoogle Scholar
  184. 184.
    Miller MF, Goodson WH, Manjili MH, Kleinstreuer N, Bisson WH, Lowe L (2017) Low-dose mixture hypothesis of carcinogenesis workshop: scientific underpinnings and research recommendations. Environ Health Perspect 125(2):163–169. CrossRefPubMedGoogle Scholar
  185. 185.
    Dimova EG, Bryant PE, Chankova SG (2008) Adaptive response: some underlying mechanisms and open questions. Genet Mol Biol 31:396–408CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  1. 1.Institut de Radioprotection et de Sureté Nucléaire (IRSN), PSE-SANTE, SESANE, LRTOXFontenay-aux-Roses CedexFrance
  2. 2.Institut de Radioprotection et de Sureté Nucléaire (IRSN), PSE-SANTE, SESANE, LRSIFontenay-aux-RosesFrance

Personalised recommendations