Low dose ionizing radiation and the immune response: what is the role of non-targeted effects?

References

• Ahmad SB, McNeill FE, Byun SH, Prestwich WV, Mothersill C, Seymour C, Armstrong A, Fernandez C. 2013. Ultra-violet light emission from HPV-G cells irradiated with low let radiation from (90)Y; consequences for radiation induced bystander effects. Dose Response. 11(4):498–516.
   PubMed Web of Science ®Google Scholar
• Al-Mayah AHJ, Irons SL, Pink RC, Carter DRF, Kadhim MA. 2012. Possible role of exosomes containing RNA in mediating nontargeted effect of ionizing radiation. Radiat Res. 177(5):539–545.
   PubMed Web of Science ®Google Scholar
• Andor N, Maley CC, Ji HP. 2017. Genomic instability in cancer: teetering on the limit of tolerance. Cancer Res. 77(9):2179–2185.
   PubMed Web of Science ®Google Scholar
• Ashrafizadeh M, Farhood B, Eleojo Musa A, Taeb S, Najafi M. 2020. The interactions and communications in tumor resistance to radiotherapy: Therapy perspectives. Int Immunopharmacol. 87:106807.
   PubMed Web of Science ®Google Scholar
• Attarwala H. 2010. TGN1412: from discovery to disaster. J Young Pharm. 2(3):332–336.
   PubMedGoogle Scholar
• 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 U S A. 98(2):473–478.
   PubMed Web of Science ®Google Scholar
• Azzam EI, Jay-Gerin J-P, Pain D. 2012. Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury. Cancer Lett. 327(1-2):48–60.
   PubMed Web of Science ®Google Scholar
• Azzam EI, Little JB. 2004. The radiation-induced bystander effect: evidence and significance. Hum Exp Toxicol. 23(2):61–65.
   PubMed Web of Science ®Google Scholar
• Barbero F, Thomas JA, Bonelli S, Balletto E, Schönrogge K. 2009. Queen ants make distinctive sounds that are mimicked by a butterfly social parasite. Science. 323(5915):782–785.
   PubMed Web of Science ®Google Scholar
• Baverstock K, Karotki AV. 2011. Towards a unifying theory of late stochastic effects of ionizing radiation. Mutat Res. 718(1-2):1–9.
   PubMed Web of Science ®Google Scholar
• Beck HL, Till JE, Grogan HA, Aanenson JW, Mohler HJ, Mohler SS, Voillequé PG. 2017. Red bone marrow and male breast doses for a cohort of atomic veterans. Rare. 187(2):221–228.
   PubMed Web of Science ®Google Scholar
• Bertucci A, Pocock RDJ, Randers-Pehrson G, Brenner DJ. 2009. Microbeam Irradiation of the C. elegans Nematode. J Radiat Res. 50 Suppl A(0 0):A49–A54.
   PubMedGoogle Scholar
• Bogdándi EN, Balogh A, Felgyinszki N, Szatmári T, Persa E, Hildebrandt G, Sáfrány 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.
   PubMed Web of Science ®Google Scholar
• Branch P, Bicknell DC, Rowan A, Bodmer WF, Karran P. 1995. Immune surveillance in colorectal carcinoma. Nat Genet. 9(3):231–232.
   PubMed Web of Science ®Google Scholar
• Calabrese E, Dhawan G, Kapoor R, Kozumbo W. 2019. Radiotherapy treatment of human inflammatory diseases and conditions: optimal dose. Hum Exp Toxicol. 38(8):888–898.
   PubMed Web of Science ®Google Scholar
• Calabrese EJ. 2005. Paradigm lost, paradigm found: the re-emergence of hormesis as a fundamental dose response model in the toxicological sciences. Environ Pollut. 138(3):379–411.
   PubMed Web of Science ®Google Scholar
• Calabrese EJ. 2017. Flaws in the LNT single-hit model for cancer risk: an historical assessment. Environ Res. 158:773–788.
   PubMed Web of Science ®Google Scholar
• Calabrese EJ. 2018. From Muller to mechanism: how LNT became the default model for cancer risk assessment. Environ Pollut. 241:289–302.
   PubMed Web of Science ®Google Scholar
• Calabrese EJ, Dhawan G. 2013. How radiotherapy was historically used to treat pneumonia: could it be useful today? Yale J Biol Med. 86(4):555–570.
   PubMedGoogle Scholar
• Cheda A, Nowosielska EM, Wrembel-Wargocka J, Janiak MK. 2008. Production of cytokines by peritoneal macrophages and splenocytes after exposures of mice to low doses of X-rays. Radiat Environ Biophys. 47(2):275–283.
   PubMed Web of Science ®Google Scholar
• Choi B, Ghosh R, Gururani MA, Shanmugam G, Jeon J, Kim J, Park S-C, Jeong M-J, Han K-H, Bae D-W, et al. 2017. Positive regulatory role of sound vibration treatment in Arabidopsis thaliana against Botrytis cinerea infection. Sci Rep. 7(1):2527.
   PubMedGoogle Scholar
• Chun SH, Park G-Y, Han YK, Kim SD, Kim JS, Lee CG, Yang K. 2012. Effect of low dose radiation on differentiation of bone marrow cells into dendritic cells. Dose Response. 11(3):374–384.
   PubMed Web of Science ®Google Scholar
• Clarke RH. 2000. Issues in the control of low-level radiation exposure . Med Confl Surviv. 16(4):411–422.
   PubMedGoogle Scholar
• Clutton SM, Townsend KMS, Walker C, Ansell JD, Wright EG. 1996. Radiation-induced genomic instability and persisting oxidative stress in primary bone marrow cultures. Carcinogenesis. 17(8):1633–1639.
   PubMed Web of Science ®Google Scholar
• Coates PJ, Lorimore SA, Wright EG. 2004. Damaging and protective cell signalling in the untargeted effects of ionizing radiation. Mutat Res. 568(1):5–20.
   PubMed Web of Science ®Google Scholar
• Cohen J, Vo NTK, Chettle DR, McNeill FE, Seymour CB, Mothersill CE. 2020. Quantifying biophoton emissions from human cells directly exposed to low-dose gamma radiation. Dose Response. 18(2):1559325820926763.
   Web of Science ®Google Scholar
• Crossland PM. 1956. Therapy of tinea capitis—the value of X-Ray epilation. Calif Med. 84(5):351–353.
   PubMedGoogle Scholar
• Csaba G. 2019. Hormesis and immunity: a review. Acta Microbiol Immunol Hung. 66(2):155–168.
   PubMed Web of Science ®Google Scholar
• Das IJ, Kalapurakal JA, Mittal BB. 2021. Caution warranted for low-dose radiation therapy for Covid-19. Br J Radiol. 94(1117):20200466.
   PubMed Web of Science ®Google Scholar
• Del Castillo R, Martinez D, Sarria GJ, Pinillos L, Garcia B, Castillo L, Carhuactocto A, Giordano FA, Sarria GR. 2020. Low-dose radiotherapy for COVID-19 pneumonia treatment: case report, procedure, and literature review. Strahlenther Onkol. 196(12):1086–1093.
   PubMed Web of Science ®Google Scholar
• Demaria S, Ng B, Devitt ML, Babb JS, Kawashima N, Liebes L, Formenti SC. 2004. Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated. Int J Radiat Oncol Biol Phys. 58(3):862–870.
   PubMed Web of Science ®Google Scholar
• El-Saghire H, Michaux A, Thierens H, Baatout S. 2013. Low doses of ionizing radiation induce immune-stimulatory responses in isolated human primary monocytes. Int J Mol Med. 32(6):1407–1414.
   PubMed Web of Science ®Google Scholar
• Ermakov AV, Kostyuk SV, Konkova MS, Egolina NA, Malinovskaya EM, Veiko NN. 2008. Extracellular DNA fragments: factors of stress signaling between X‐irradiated and nonirradiated human lymphocytes. Ann N Y Acad Sci. 1137(1):41–46.
   PubMedGoogle Scholar
• Farhood B, Khodamoradi E, Hoseini-Ghahfarokhi M, Motevaseli E, Mirtavoos-Mahyari H, Eleojo Musa A, Najafi M. 2020. TGF-β in radiotherapy: Mechanisms of tumor resistance and normal tissues injury. Pharmacol Res. 155:104745.
   PubMed Web of Science ®Google Scholar
• Feinendegen LE. 2005. Evidence for beneficial low level radiation effects and radiation hormesis. Br J Radiol. 78(925):3–7.
   PubMed Web of Science ®Google Scholar
• Fernandez-Palomo C, Schültke E, Bräuer-Krisch E, Laissue JA, Blattmann H, Seymour C, Mothersill C. 2016. Investigation of abscopal and bystander effects in immunocompromised mice after exposure to pencilbeam and microbeam synchrotron radiation. Health Phys. 111(2):149–159.
   PubMed Web of Science ®Google Scholar
• Folley JH, Borges W, Yamawaki T. 1952. Incidence of leukemia in survivors of the atomic bomb in Hiroshima and Nagasaki, Japan. Am J Med. 13(3):311–321.
   PubMed Web of Science ®Google Scholar
• Franchi N, Ballarin L. 2017. Immunity in protochordates: the tunicate perspective. Front Immunol. 8:674.
   PubMed Web of Science ®Google Scholar
• Fujiwara S, Carter RL, Akiyama M, Akahoshi M, Kodama K, Shimaoka K, Yamakido M. 1994. Autoantibodies and Immunoglobulins among Atomic Bomb Survivors. J Radiat Res. 137(1):89–95.
   Google Scholar
• Frongia F, Forti L, Arru L. 2020. Sound perception and its effects in plants and algae. Plant Signal Behav. 15(12):1828674.
   PubMed Web of Science ®Google Scholar
• Gardner MJ. 1991. Father's occupational exposure to radiation and the raised level of childhood leukemia near the Sellafield nuclear plant. Environ Health Perspect. 94:5–7.
   PubMed Web of Science ®Google Scholar
• Gluzman DF, Zavelevich MP, Philchenkov AA, Koval SV, Bezhenar TO. 2021. Immunodeficiency-associated lymphoproliferative disorders and lymphoid neoplasms in post-COVID-19 pandemic era. Exp Oncol. 43(1):87–91.
   PubMedGoogle Scholar
• Guo X, Sun J, Bian P, Chen L, Zhan F, Wang J, Xu A, Wang Y, Hei TK, Wu L. 2013. Radiation-Induced Bystander Signaling from Somatic Cells to Germ Cells in Caenorhabditis elegans. Radiat Res. 180(3):268–275.
   PubMed Web of Science ®Google Scholar
• Hanekamp YN, Giordano J, Hanekamp JC, Khan MK, Limper M, Venema CS, Vergunst SD, Verhoeff JJC, Calabrese EJ. 2020. Immunomodulation through low-dose radiation for severe COVID-19: lessons from the past and new developments. Dose Response. 18(3):1559325820956800.
   Web of Science ®Google Scholar
• Hei TK, Zhou H, Ivanov VN, Hong M, Lieberman HB, Brenner DJ, Amundson SA, Geard CR. 2008. Mechanism of radiation-induced bystander effects: a unifying model. J Pharm Pharmacol. 60(8):943–950.
   PubMed Web of Science ®Google Scholar
• Heineke H. 1905. Experimentelle untersuchungen über die einwirkung der röntgenstrahlen auf das knochenmark, nebst einigen bemerkungen über die röntgentherapie der leukämie und pseudoleukämie und des sarcoms. langenbeck’s. Deutsche Zeitschrift f Chirurgie. 78(1-3):196–230.
   Google Scholar
• Hektoen L. 1918. Further studies on the effects of the roentgen ray on antibody-production. J Infect Dis. 22(1):28–33.
   Google Scholar
• Hellweg CE. 2015. The Nuclear Factor κB pathway: a link to the immune system in the radiation response. Cancer Lett. 368(2):275–289.
   PubMed Web of Science ®Google Scholar
• Heyd R, Tselis N, Ackermann H, Röddiger SJ, Zamboglou N. 2007. Radiation therapy for painful heel spurs: results of a prospective randomized study. Strahlenther Onkol. 183(1):3–9.
   PubMed Web of Science ®Google Scholar
• Hollowell JG, Littlefield LG. 1968. Chromosome damage induced by plasma of X-rayed patients: an indirect effect of X-Ray∗. Proc Soc Exp Biol Med. 129(1):240–244.
   PubMed Web of Science ®Google Scholar
• Hsu W-L, Preston DL, Soda M, Sugiyama H, Funamoto S, Kodama K, Kimura A, Kamada N, Dohy H, Tomonaga M, et al. 2013. The incidence of leukemia, lymphoma, and multiple myeloma among atomic bomb survivors. Radiat Res. 179(3):1950–2001.
   Web of Science ®Google Scholar
• Ilnytskyy Y, Kovalchuk O. 2011. Non-targeted radiation effects-an epigenetic connection. Mutat Res. 714(1-2):113–125.
   PubMed Web of Science ®Google Scholar
• Jacobson LO, Simmons EL, Bethard WF, Marks EK, Robson MJ. 1950. The influence of the spleen on hematopoietic recovery after irradiation injury. Proc Soc Exp Biol Med. 73(3):455–459.
   Web of Science ®Google Scholar
• Janiak MK, Wincenciak M, Cheda A, Nowosielska EM, Calabrese EJ. 2017. Cancer immunotherapy: how low-level ionizing radiation can play a key role. Cancer Immunol Immunother. 66(7):819–832.
   PubMed Web of Science ®Google Scholar
• Jansen JThM, Broerse JJ, Zoetelief J, Klein C, Seegenschmiedt HM. 2005. Estimation of the carcinogenic risk of radiotherapy of benign diseases from shoulder to heel. Radiother Oncol. 76(3):270–277.
   PubMed Web of Science ®Google Scholar
• Jargin S. 2012. Hormesis and radiation safety norms. Hum Exp Toxicol. 31(7):671–675.
   PubMed Web of Science ®Google Scholar
• Jella KK, Rani S, O'Driscoll L, McClean B, Byrne HJ, Lyng FM. 2014. Exosomes are involved in mediating radiation induced bystander signaling in human keratinocyte cells. Radiat Res. 181(2):138–145.
   PubMed Web of Science ®Google Scholar
• Jerne NK. 1973. The immune system. Sci Am. 229(1):52–63.
   PubMed Web of Science ®Google Scholar
• Joiner MC, Marples B, Lambin P, Short SC, Turesson I. 2001. Low-dose hypersensitivity: current status and possible mechanisms. Inter J Rad Oncol Biol Phys. 49(2):379–389.
   PubMed Web of Science ®Google Scholar
• Kadhim MA, Lorimore SA, Townsend KMS, Goodhead DT, Buckle VJ, Wright EG. 1995. Radiation-induced genomic instability: delayed cytogenetic aberrations and apoptosis in primary human bone marrow cells. Int J Radiat Biol. 67(3):287–293.
   PubMed Web of Science ®Google Scholar
• Kadhim MA, Macdonald DA, Goodhead DT, Lorimore SA, Marsden SJ, Wright EG. 1992. Transmission of chromosomal instability after plutonium alpha-particle irradiation. Nature. 355(6362):738–740.
   PubMed Web of Science ®Google Scholar
• Kadhim MA, Mayah A, Brooks SA. 2020. Does direct and indirect exposure to ionising radiation influence the metastatic potential of breast cancer cells. Cancers. 12(1):236.
   Web of Science ®Google Scholar
• Kalpana KB, Devipriya N, Thayalan K, Menon VP. 2010. Protection against X-ray radiation-induced cellular damage of human peripheral blood lymphocytes by an aminothiazole derivative of dendrodoine. Chem Biol Interact. 186(3):267–274.
   PubMed Web of Science ®Google Scholar
• Karran P. 1996. Microsatellite instability and DNA mismatch repair in human cancer. Semin Cancer Biol. 7(1):15–24.
   PubMed Web of Science ®Google Scholar
• Karran P, Bignami M. 1994. DNA damage tolerance, mismatch repair and genome instability. Bioessays. 16(11):833–839.
   PubMed Web of Science ®Google Scholar
• Kefayat A, Ghahremani F. 2020. Low dose radiation therapy for COVID-19 pneumonia: a double-edged sword. Radiother Oncol. 147:224–225.
   PubMed Web of Science ®Google Scholar
• Kim GJ, Fiskum GM, Morgan WF. 2006. A role for mitochondrial dysfunction in perpetuating radiation-induced genomic instability. Cancer Res. 66(21):10377–10383.
   PubMed Web of Science ®Google Scholar
• Klug F, Prakash H, Huber PE, Seibel T, Bender N, Halama N, Pfirschke C, Voss RH, Timke C, Umansky L, et al. 2013. Low-dose irradiation programs macrophage differentiation to an iNOS+/M1 phenotype that orchestrates effective T cell immunotherapy. Cancer Cell 24(5):589–602.
   PubMed Web of Science ®Google Scholar
• Kumar A, Dey AD, Behl T, Chadha S, Aggarwal V. 2021. Exploring the multifocal therapeutic approaches in COVID-19: a ray of hope. Int Immunopharmacol. 90:107156.
   PubMed Web of Science ®Google Scholar
• Kurd N, Robey EA. 2016. T-cell selection in the thymus: a spatial and temporal perspective. Immunol Rev. 271(1):114–126.
   PubMed Web of Science ®Google Scholar
• Lara PC, Burgos J, Macias D. 2020. Low dose lung radiotherapy for COVID-19 pneumonia. The rationale for a cost-effective anti-inflammatory treatment. Clin Transl Radiat Oncol. 23:27–29.
   PubMed Web of Science ®Google Scholar
• Laurier D, Richardson DB, Cardis E, Daniels RD, Gillies M, O'Hagan J, Hamra GB, Haylock R, Leuraud K, Moissonnier M, et al. 2017. The international nuclear workers study (Inworks): a collaborative epidemiological study to improve knowledge about health effects of protracted low-dose exposure. Radiat Prot Dosimetry. 173(1-3):21–25.
   PubMed Web of Science ®Google Scholar
• Le M, Fernandez-Palomo C, McNeill FE, Seymour CB, Rainbow AJ, Mothersill CE. 2017. Exosomes are released by bystander cells exposed to radiation-induced biophoton signals: Reconciling the mechanisms mediating the bystander effect. PLoS One. 12(3):e0173685.
   PubMed Web of Science ®Google Scholar
• Le M, McNeill FE, Seymour C, Rainbow AJ, Mothersill CE. 2015. An observed effect of ultraviolet radiation emitted from beta-irradiated HaCaT Cells upon non-beta-irradiated bystander cells. Radiation Res. 183(3):279–290.
   PubMed Web of Science ®Google Scholar
• Le M, McNeill FE, Seymour CB, Rusin A, Diamond K, Rainbow AJ, Murphy J, Mothersill CE. 2018. Modulation of oxidative phosphorylation (OXPHOS) by radiation- induced biophotons. Environ Res. 163:80–87.
   PubMed Web of Science ®Google Scholar
• Litman GW, Cannon JP, Dishaw LJ. 2005. Reconstructing immune phylogeny: new perspectives. Nat Rev Immunol. 5(11):866–879.
   PubMed Web of Science ®Google Scholar
• Litman GW, Rast JP, Shamblott MJ, Haire RN, Hulst M, Roess W, Litman RT, Hinds-Frey KR, Zilch A, Amemiya CT. 1993. Phylogenetic diversification of immunoglobulin genes and the antibody repertoire. Mol Biol Evol. 10(1):60–72.
   PubMed Web of Science ®Google Scholar
• Little MP. 2010. Do non-targeted effects increase or decrease low dose risk in relation to the linear-non-threshold (LNT) model? Mutat Res. 687(1-2):17–27.
   PubMed Web of Science ®Google Scholar
• Littlefield LG, Hollowell JG, Pool WH. 1969. Chromosomal aberrations induced by plasma from irradiated patients: an indirect effect of X radiation. Further observations and studies of a control population. Radiology. 93(4):879–886.
   PubMed Web of Science ®Google Scholar
• Liu S-Z. 2003. On Radiation Hormesis Expressed in the Immune System. Crit Rev Toxicol. 33(3-4):431–441.
   PubMed Web of Science ®Google Scholar
• Liu Y, Sawalha AH, Lu Q. 2021. COVID-19 and autoimmune diseases. Curr Opin Rheumatol. 33(2):155–162.
   PubMed Web of Science ®Google Scholar
• Lord BI. 1999. Transgenerational susceptibility to leukaemia induction resulting from preconception, paternal irradiation. Int J Radiat Biol. 75(7):801–810.
   PubMed Web of Science ®Google Scholar
• Lorimore SA, Chrystal JA, Robinson JI, Coates PJ, Wright EG. 2008. Chromosomal instability in unirradiated hemaopoietic cells induced by macrophages exposed in vivo to ionizing radiation. Cancer Res. 68(19):8122–8126.
   PubMed Web of Science ®Google Scholar
• Lyng FM, Howe OL, McClean B. 2011. Reactive oxygen species-induced release of signalling factors in irradiated cells triggers membrane signalling and calcium influx in bystander cells. Int J Radiat Biol. 87(7):683–695.
   PubMed Web of Science ®Google Scholar
• Lyng FM, Maguire P, McClean B, Seymour C, Mothersill C. 2006. The Involvement of calcium and MAP kinase signaling pathways in the production of radiation-induced bystander effects. Radiat Res. 165(4):400–409.
   PubMed Web of Science ®Google Scholar
• Lyng FM, Seymour CB, Mothersill C. 2000. Production of a signal by irradiated cells which leads to a response in unirradiated cells characteristic of initiation of apoptosis. Br J Cancer. 83(9):1223–1230.
   PubMed Web of Science ®Google Scholar
• Lyng FM, Seymour CB, Mothersill C. 2001. Oxidative stress in cells exposed to low levels of ionizing radiation. Biochem Soc Transac. 29(2):350–353.
   PubMedGoogle Scholar
• Lyng FM, Seymour CB, Mothersill C. 2002. Initiation of apoptosis in cells exposed to medium from the progeny of irradiated cells: a possible mechanism for bystander-induced genomic instability? Radiat Res. 157(4):365–370.
   PubMed Web of Science ®Google Scholar
• Maguire P, Mothersill C, McClean B, Seymour C, Lyng FM. 2007. Modulation of radiation responses by pre-exposure to irradiated cell conditioned medium. Radiat Res. 167(4):485–492.
   PubMed Web of Science ®Google Scholar
• Maiese A, Manetti AC, La Russa R, Di Paolo M, Turillazzi E, Frati P, Fineschi V. 2021. Autopsy findings in COVID-19-related deaths: a literature review. Forensic Sci Med Pathol. 17(2):279–296.
   PubMed Web of Science ®Google Scholar
• Marozik P, Mothersill C, Seymour CB, Mosse I, Melnov S. 2007. Bystander effects induced by serum from survivors of the Chernobyl accident. Exp Hematol. 35(4 Suppl 1):55–63.
   PubMed Web of Science ®Google Scholar
• Matarèse BFE, Lad J, Seymour C, Schofield PN, Mothersill C. 2020. Bio-acoustic signaling; exploring the potential of sound as a mediator of low-dose radiation and stress responses in the environment. Inter J Rad Biol. 0(0):1–15.
   PubMedGoogle Scholar
• McBride WH, Chiang C-S, Olson JL, Wang C-C, Hong J-H, Pajonk F, Dougherty GJ, Iwamoto KS, Pervan M, Liao Y-P. 2004. A sense of danger from radiation. Radiat Res. 162(1):1–19.
   PubMed Web of Science ®Google Scholar
• McBride WH, Ganapathy E, Lee M-H, Nesseler JP, Nguyen C, Schaue D. 2017. A perspective on the impact of radiation therapy on the immune rheostat. Br J Radiol. 90(1078):20170272.
   PubMed Web of Science ®Google Scholar
• McKeown SR, Hatfield P, Prestwich RJ, Shaffer RE, Taylor RE. 2015. Radiotherapy for benign disease; assessing the risk of radiation-induced cancer following exposure to intermediate dose radiation. Br J Radiol. 88(1056):20150405.
   PubMed Web of Science ®Google Scholar
• McMahon SJ. 2018. The linear quadratic model: usage, interpretation and challenges. Phys Med Biol. 64(1):01TR01.
   PubMed Web of Science ®Google Scholar
• Melief CJM. 2003. Mini-review: Regulation of cytotoxic T lymphocyte responses by dendritic cells: peaceful coexistence of cross-priming and direct priming? Eur J Immunol. 33(10):2645–2654.
   PubMed Web of Science ®Google Scholar
• Mitchel REJ. 2006. Low Doses of Radiation Reduce Risk In Vivo. Dose Response. 5(1):1–10.
   PubMedGoogle Scholar
• Moattari CR, Granstein RD. 2021. Neuropeptides and neurohormones in immune, inflammatory and cellular responses to ultraviolet radiation. Acta Physiol (Oxf). 232(1):e13644.
   PubMed Web of Science ®Google Scholar
• Mohammadi A, Blesso CN, Barreto GE, Banach M, Majeed M, Sahebkar A. 2019. Macrophage plasticity, polarization and function in response to curcumin, a diet-derived polyphenol, as an immunomodulatory agent. J Nutr Biochem. 66:1–16.
   PubMed Web of Science ®Google Scholar
• Mole RH. 1953. Whole Body irradiation; radiobiology or medicine? Br J Radiol. 26(305):234–241.
   PubMed Web of Science ®Google Scholar
• Montero A, Arenas M, Algara M. 2021. Low-dose radiation therapy: could it be a game-changer for COVID-19? Clin Transl Oncol. 23(1):1–4.
   PubMed Web of Science ®Google Scholar
• Morgan WF, Bair WJ. 2013. Issues in low dose radiation biology: the controversy continues. a perspective. Radiat Res. 179(5):501–510.
   PubMed Web of Science ®Google Scholar
• Morgan WF, Sowa MB. 2015. Non-targeted effects induced by ionizing radiation: mechanisms and potential impact on radiation induced health effects. Cancer Lett. 356(1):17–21.
   PubMed Web of Science ®Google Scholar
• Morrissy AS, Garzia L, Shih DJH, Zuyderduyn S, Huang X, Skowron P, Remke M, Cavalli FMG, Ramaswamy V, Lindsay PE, et al. 2016. Divergent clonal selection dominates medulloblastoma at recurrence. Nature. 529(7586):351–357.
   PubMed Web of Science ®Google Scholar
• Mosse IB. 2012. Genetic effects of ionizing radiation-some questions with no answers. J Environ Radioact. 112:70–75.
   PubMed Web of Science ®Google Scholar
• Mothersill C, Rusin A, Fernandez-Palomo C, Seymour C. 2018. History of bystander effects research 1905-present; what is in a name? Int J Radiat Biol. 94(8):696–707.
   PubMed Web of Science ®Google Scholar
• Mothersill C, Rusin A, Seymour C. 2017. Low doses and non-targeted effects in environmental radiation protection; where are we now and where should we go? Environ Res. 159:484–490.
   PubMed Web of Science ®Google Scholar
• Mothersill C, Seymour C. 1997. Lethal mutations and genomic instability. Int J Radiat Biol. 71(6):751–758.
   PubMed Web of Science ®Google Scholar
• Mothersill C, Seymour C. 2009. Communication of ionising radiation signals-a tale of two fish. Int J Radiat Biol. 85(11):909–919.
   PubMed Web of Science ®Google Scholar
• Mothersill C, Seymour C. 2013. Radiation-induced bystander effects and stress-induced mutagenesis. In: Mittelman D, editor. Stress-induced mutagenesis. New York (NY): Springer; p. 199–222.
   Google Scholar
• 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):256–262.
   PubMed Web of Science ®Google Scholar
• Mothersill C, Seymour CB, Joiner MC. 2002. Relationship between radiation-induced low-dose hypersensitivity and the bystander effect. Rare. 157(5):526–532.
   PubMed Web of Science ®Google Scholar
• Mothersill C, Smith RW, Fazzari J, McNeill F, Prestwich W, Seymour CB. 2012. Evidence for a physical component to the radiation-induced bystander effect? Int J Radiat Biol. 88(8):583–591.
   PubMed Web of Science ®Google Scholar
• Mothersill C, Stamato TD, Perez ML, Cummins R, Mooney R, Seymour CB. 2000. Involvement of energy metabolism in the production of ‘bystander effects’ by radiation. Br J Cancer. 82(10):1740–1746.
   PubMed Web of Science ®Google Scholar
• Mottram ME, Hill HA. 1949. Radiation therapy of ringworm of the scalp. Calif Med. 70(3):189–193.
   PubMedGoogle Scholar
• Muecke R, Micke O, Reichl B, Heyder R, Prott F-J, Seegenschmiedt MH, Glatzel M, Schneider O, Schäfer U, Kundt G. 2007. Demographic, clinical and treatment related predictors for event-free probability following low-dose radiotherapy for painful heel spurs – a retrospective multicenter study of 502 patients. Acta Oncologica. 46(2):239–246.
   PubMed Web of Science ®Google Scholar
• Müller WE, Blumbach B, Müller IM. 1999. Evolution of the innate and adaptive immune systems: relationships between potential immune molecules in the lowest metazoan phylum (Porifera) and those in vertebrates. Transplantation. 68(9):1215–1227.
   PubMed Web of Science ®Google Scholar
• Müller WEG. 2001. Review: How was metazoan threshold crossed? The hypothetical Urmetazoa. Compar Biochem Physiol Part A Mol Integr Physiol. 129(2-3):433–460.
   PubMed Web of Science ®Google Scholar
• Müller WEG, Wiens M, Gamulin AT, Schröder V, Müller Im HC. 2004. Bauplan of Urmetazoa: basis for genetic complexity of metazoa. Int Rev Cytol. 235:53–92.
   Google Scholar
• Murphy JB, Liu JH, Sturm E. 1922. Studies on X-ray effects : ix. the action of serum from x-rayed animals on lymphoid cells in vitro. J Exp Med. 35(3):373–384.
   PubMedGoogle Scholar
• Murphy JB, Morton JJ. 1915. The lymphocyte in natural and induced resistance to transplanted cancer : II. studies in lymphoid activity. J Exp Med. 22(2):204–211.
   PubMedGoogle Scholar
• Murphy JB, Taylor HD. 1918. The lymphocyte in natural and induced resistance to transplanted cancer : III. the effect of X-rays on artificially induced immunity. J Exp Med. 28(1):1–9.
   PubMedGoogle Scholar
• Nagasawa H, Little JB. 1992. Induction of sister chromatid exchanges by extremely low doses of α-particles. Cancer Res. 52(22):6394–6396.
   PubMed Web of Science ®Google Scholar
• Nakahara W, Murphy JB. 1920. Studies on X-ray effects. J Exp Med. 31(1):13–29.
   PubMedGoogle Scholar
• Nakahira K, Haspel JA, Rathinam VA, Lee S-J, Dolinay T, Lam HC, Englert JA, Rabinovitch M, Cernadas M, Kim HP, et al. 2011. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome . Nat Immunol. 12(3):222–230.
   PubMed Web of Science ®Google Scholar
• Nakanishi M, Tanaka K, Shintani T, Takahashi T, Kamada N. 1999. Chromosomal instability in acute myelocytic leukemia and myelodysplastic syndrome patients among atomic bomb survivors. JRR. 40(2):159–167.
   PubMed Web of Science ®Google Scholar
• Nicholson LB. 2016. The immune system. Essays Biochem. 60(3):275–301.
   PubMed Web of Science ®Google Scholar
• Nicolò P, Matteo C, Daniela P, Aiti V. 2016. Chapter 13 - inflammatory response of the ascidian ciona intestinalis. In: Ballarin L, Cammarata M, editors. Lessons in immunity. London (UK): Academic Press; p. 177–192.
   Google Scholar
• Niewald M, Seegenschmiedt MH, Micke O, Graeber S, Muecke R, Schaefer V, Scheid C, Fleckenstein J, Licht N, Ruebe C. 2012. Randomized, multicenter trial on the effect of radiation therapy on plantar fasciitis (painful heel spur) comparing a standard dose with a very low dose: mature results after 12 months’ follow-up. Inter J Rad Oncol Biol Phys. 84(4):e455–e462.
   PubMed Web of Science ®Google Scholar
• Nikitaki Z, Mavragani IV, Laskaratou DA, Gika V, Moskvin VP, Theofilatos K, Vougas K, Stewart RD, Georgakilas AG. 2016. Systemic mechanisms and effects of ionizing radiation: a new 'old' paradigm of how the bystanders and distant can become the players. Semin Cancer Biol. 37-38:77–95.
   PubMed Web of Science ®Google Scholar
• Nowosielska EM, Cheda A, Wrembel-Wargocka J, Janiak MK. 2012. Effect of low doses of low-let radiation on the innate anti-tumor reactions in radioresistant and radiosensitive mice. Dose Response. 10(4):500–515.
   PubMed Web of Science ®Google Scholar
• Nugent SME, Mothersill CE, Seymour C, McClean B, Lyng FM, Murphy JEJ. 2007. Increased mitochondrial mass in cells with functionally compromised mitochondria after exposure to both direct gamma radiation and bystander factors. Radiat Res. 168(1):134–142.
   PubMed Web of Science ®Google Scholar
• Olivieri G, Bodycote J, Wolff S. 1984. Adaptive response of human lymphocytes to low concentrations of radioactive thymidine. Science. 223(4636):594–597.
   PubMed Web of Science ®Google Scholar
• Padgham M. 2004. Reverberation and frequency attenuation in forests-implications for acoustic communication in animals. J Acoust Soc Am. 115(1):402–410.
   PubMed Web of Science ®Google Scholar
• Parsons WB, Watkins CH, Pease GL, Childs DS. 1954. Changes in sternal marrow following roentgen-ray therapy to the spleen in chronic granulocytic leukemia. Cancer. 7(1):179–189.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Prasanna A, Ahmed MM, Mohiuddin M, Coleman CN. 2014. Exploiting sensitization windows of opportunity in hyper and hypo-fractionated radiation therapy. J Thorac Dis. 6(4):287–302.
   PubMed Web of Science ®Google Scholar
• Prasanna PG, Woloschak GE, DiCarlo AL, Buchsbaum JC, Schaue D, Chakravarti A, Cucinotta FA, Formenti SC, Guha C, Hu DJ, et al. 2020. Low-Dose Radiation Therapy (LDRT) for COVID-19: benefits or risks? Radiat Res. 194(5):452–464.
   PubMed Web of Science ®Google Scholar
• Prise K, Folkard M, D. Michael (INVITED) B. 2003. A review of the bystander effect and its implications for low-dose exposure. Radiat Prot Dosimetry. 104(4):347–355.
   PubMed Web of Science ®Google Scholar
• Prise KV, Belyakov OC, Newman H, Patel S, Schettino G, Folkard MD, Michael (INVITED) B. 2002. Non-targeted Effects of radiation: bystander responses in cell and tissue models. Radiat Prot Dosimetry. 99(1-4):223–226.
   PubMed Web of Science ®Google Scholar
• Pusey WA, Caldwell E. 1903. The practical application of the Röntgen rays in therapeutics and diagnosis. Philadelphia: Saunders.
   Google Scholar
• Rinkevich B, Weissman IL. 1992. Allogeneic resorption in colonial protochordates: consequences of nonself recognition. Dev Comp Immunol. 16(4):275–286.
   PubMed Web of Science ®Google Scholar
• Rödel F, Keilholz L, Herrmann M, Sauer R, Hildebrandt G. 2007. Radiobiological mechanisms in inflammatory diseases of low-dose radiation therapy. Int J Radiat Biol. 83(6):357–366.
   PubMed Web of Science ®Google Scholar
• Rusin A, Seymour C, Mothersill C. 2018. Chronic fatigue and immune deficiency syndrome (CFIDS), cellular metabolism, and ionizing radiation: a review of contemporary scientific literature and suggested directions for future research. Int J Radiat Biol. 94(3):212–228.
   PubMed Web of Science ®Google Scholar
• Russ S, Chambers H, Scott GM, Mottram JC. 1919. Experimental studies with small doses of x rays. The Lancet. 193(4991):692–695.
   Google Scholar
• Ryan LA, Seymour CB, O'Neill-Mehlenbacher A, Mothersill CE. 2008. Radiation-induced adaptive response in fish cell lines. J Environ Radioact. 99(4):739–747.
   PubMed Web of Science ®Google Scholar
• Ryan MT, Poston JW. 2006. A half century of health physics: 50th anniversary of the health physics society. Baltimore (MD): Lippincott Williams & Wilkins.
   Google Scholar
• Salomaa S, Bouffler SD, Atkinson MJ, Cardis E, Hamada N. 2020. Is there any supportive evidence for low dose radiotherapy for COVID-19 pneumonia? Int J Radiat Biol. 96(10):1228–1235.
   PubMed Web of Science ®Google Scholar
• Schaue D. 2017. A century of radiation therapy and adaptive immunity. Front Immunol. 8:431.
   PubMed Web of Science ®Google Scholar
• Schaue D, Kachikwu EL, McBride WH. 2012. Cytokines in radiobiological responses: a review. Radiat Res. 178(6):505–523.
   PubMed Web of Science ®Google Scholar
• Schaue D, Marples B, Trott KR. 2002. The effects of low-dose X-irradiation on the oxidative burst in stimulated macrophages. Null. 78(7):567–576.
   Google Scholar
• Schirrmacher V. 2020. Mitochondria at work: new insights into regulation and dysregulation of cellular energy supply and metabolism. Biomedicines. 8(11):526.
   Web of Science ®Google Scholar
• Schneider O, Stückle CA, Bosch E, Gott C, Adamietz IA. 2004. Effectiveness and prognostic factors of radiotherapy for painful plantar heel spurs. Strahlenther Onkol. 180(8):502–509.
   PubMed Web of Science ®Google Scholar
• Scott BR. 2008. It's time for a new low-dose-radiation risk assessment paradigm-one that acknowledges hormesis. Dose Response. 6(4):333–351.
   PubMed Web of Science ®Google Scholar
• Scott BR. 2017. Small radiation doses enhance natural barriers to cancer. J Am Physic Surg. 22(4):105.
   Google Scholar
• Scott WR. 1939. X-ray therapy in the treatment of acute pneumonia. Radiology. 33(3):331–349.
   Google Scholar
• Seymour CB, Mothersill C, Alper T. 1986. High yields of lethal mutations in somatic mammalian cells that survive ionizing radiation. Int J Radiat Biol Relat Stud Phys Chem Med. 50(1):167–179.
   PubMed Web of Science ®Google Scholar
• Shamblott MJ, Litman GW. 1989. Complete nucleotide sequence of primitive vertebrate immunoglobulin light chain genes. Proc Natl Acad Sci USA. 86(12):4684–4688.
   PubMed Web of Science ®Google Scholar
• Shao C, Lyng FM, Folkard M, Prise KM. 2006. Calcium fluxes modulate the radiation-induced bystander responses in targeted glioma and fibroblast cells. Radiat Res. 166(3):479–487.
   PubMed Web of Science ®Google Scholar
• Shimura T, Kunugita N. 2016. Mitochondrial reactive oxygen species-mediated genomic instability in low-dose irradiated human cells through nuclear retention of cyclin D1. Cell Cycle. 15(11):1410–1414.
   PubMed Web of Science ®Google Scholar
• Sisakht M, Darabian M, Mahmoodzadeh A, Bazi A, Shafiee SM, Mokarram P, Khoshdel Z. 2020. The role of radiation induced oxidative stress as a regulator of radio-adaptive responses. Int J Radiat Biol. 96(5):561–576.
   PubMed Web of Science ®Google Scholar
• Smith LC, Davidson EH. 1994. The echinoderm immune system. characters shared with vertebrate immune systems and characters arising later in deuterostome phylogeny. Ann N Y Acad Sci. 712(1):213–226.
   PubMedGoogle Scholar
• Souto J. 1962. Tumour development in the rat induced by blood of irradiated animals. Nature. 195(4848):1317–1318.
   PubMed Web of Science ®Google Scholar
• Spix C, Schmiedel S, Kaatsch P, Schulze-Rath R, Blettner M. 2008. Case-control study on childhood cancer in the vicinity of nuclear power plants in Germany 1980-2003. Eur J Cancer. 44(2):275–284.
   PubMed Web of Science ®Google Scholar
• Surinov BP, Isaeva VG, Dukhova NN. 2004. Postirradiation volatile secretions of mice: syngeneic and allogeneic immune and behavioral effects. Bull Exp Biol Med. 138(4):384–386.
   PubMed Web of Science ®Google Scholar
• Sutou S. 2018. Low-dose radiation from A-bombs elongated lifespan and reduced cancer mortality relative to un-irradiated individuals. Genes Environ. 40:26.
   PubMed Web of Science ®Google Scholar
• Szatmári T, Persa E, Kis E, Benedek A, Hargitai R, Sáfrány G, Lumniczky K. 2019. Extracellular vesicles mediate low dose ionizing radiation-induced immune and inflammatory responses in the blood. Int J Radiat Biol. 95(1):12–22.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Taher M, Tik N, Susanti D. 2021. Drugs intervention study in COVID-19 management. Drug Metabol Personal Ther. 36(2):87–98.
   PubMedGoogle Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Taylor HD, Witherbee WD, Murphy JB. 1919. Studies on X-ray effects. J Exp Med. 29(1):53–73.
   PubMedGoogle Scholar
• Till JE, Beck HL, Aanenson JW, Grogan HA, Mohler HJ, Mohler SS, Voillequé PG. 2018. Dosimetry associated with veterans who participated in nuclear weapons testing. Int J Radiat Biol . 0(0):1–9.
   Google Scholar
• Tobaiqy M, Qashqary M, Al-Dahery S, Mujallad A, Hershan AA, Kamal MA, Helmi N. 2020. Therapeutic management of patients with COVID-19: a systematic review. Infect Prevent Prac. 2(3):100061.
   PubMedGoogle Scholar
• Tuncay Cagatay S, Mayah A, Mancuso M, Giardullo P, Pazzaglia S, Saran A, Daniel A, Traynor D, Meade AD, Lyng F. 2020. Phenotypic and functional characteristics of exosomes derived from irradiated mouse organs and their role in the mechanisms driving non-targeted effects. Int J Mol Sci. 21(21):8389.
   PubMed Web of Science ®Google Scholar
• Ullrich SE, Byrne SN. 2012. The immunologic revolution: photoimmunology. J Invest Dermatol. 132(3 Pt 2):896–905.
   PubMed Web of Science ®Google Scholar
• United Nations Scientific Committee on the Effects of Atomic Radiation 2017. Sources, Effects and Risks of Ionizing Radiation, UNSCEAR 2012 Report: Report to the General Assembly, with Scientific Annexes A and B. Geneva: UN; [accessed 2021 Mar 19].
   Google Scholar
• Valerie K, Yacoub A, Hagan MP, Curiel DT, Fisher PB, Grant S, Dent P. 2007. Radiation-induced cell signaling: inside-out and outside-in. Mol Cancer Ther. 6(3):789–801.
   PubMed Web of Science ®Google Scholar
• Wambersie A, Jr Caswell PMD, Menzel Hg RS. 2000. The International Commission on Radiation Units and Measurements (ICRU): Activities and Future Plans. ICRP Publication. 60:20–22.
   Google Scholar
• Warthin AS. 1907. The changes produced in the kidneys by röntgen irradiation. Am J Med Sci (1827–1924). 133(5):736.
   Google Scholar
• Watson GE, Lorimore SA, Macdonald DA, Wright EG. 2000. Chromosomal instability in unirradiated cells induced in vivo by a bystander effect of ionizing radiation. Cancer Res. 60(20):5608–5611.
   PubMed Web of Science ®Google Scholar
• Yahyapour R, Amini P, Rezapour S, Cheki M, Rezaeyan A, Farhood B, Shabeeb D, Musa AE, Fallah H, Najafi M. 2018. Radiation-induced inflammation and autoimmune diseases. Mil Med Res. 5(1):9.
   PubMed Web of Science ®Google Scholar
• York JM, Blevins NA, Meling DD, Peterlin MB, Gridley DS, Cengel KA, Freund GG. 2012. The biobehavioral and neuroimmune impact of low-dose ionizing radiation. Brain Behav Immun. 26(2):218–227.
   PubMed Web of Science ®Google Scholar
• Yoshida GJ, Saya H. 2021. Molecular pathology underlying the robustness of cancer stem cells. Regen Ther. 17:38–50.
   PubMedGoogle Scholar
• Zahnreich S, Rösler H-P, Schwanbeck C, Karle H, Schmidberger H. 2020. Radiation-induced DNA double-strand breaks in peripheral leukocytes and therapeutic response of heel spur patients treated by orthovoltage X-rays or a linear accelerator. Strahlenther Onkol. 196(12):1116–1127.
   PubMed Web of Science ®Google Scholar