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The intercellular communications mediating radiation-induced bystander effects and their relevance to environmental, occupational, and therapeutic exposures

ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon
Pages 964-982 | Received 26 Mar 2022, Accepted 10 May 2022, Published online: 27 May 2022

References

  • Aasen T, Leithe E, Graham SV, Kameritsch P, Mayan MD, Mesnil M, Pogoda K, Tabernero A. 2019. Connexins in cancer: bridging the gap to the clinic. Oncogene. 38(23):4429–4451.
  • Abdelrazzak AB, Pottgießer SJ, Hill MA, O'Neill P, Bauer G. 2016. Enhancement of peroxidase release from non-malignant and malignant cells through low-dose irradiation with different radiation quality. Radiat Res. 185(2):199–213.
  • Abramowicz A, Wojakowska A, Marczak L, Lysek-Gladysinska M, Smolarz M, Story MD, Polanska J, Widlak P, Pietrowska M. 2019. Ionizing radiation affects the composition of the proteome of extracellular vesicles released by head-and-neck cancer cells in vitro. J Radiat Res. 60(3):289–297.
  • Aguirre A, Shoji KF, Saez JC, Henriquez M, Quest AF. 2013. FasL-triggered death of Jurkat cells requires caspase 8-induced, ATP-dependent cross-talk between Fas and the purinergic receptor P2X(7). J Cell Physiol. 228(2):485–493.
  • Al-Mayah AH, Bright S, Chapman K, Irons S, Luo P, Carter D, Goodwin E, Kadhim M. 2015. The non-targeted effects of radiation are perpetuated by exosomes. Mutat Res. 772:38–45.
  • Al-Mayah AH, Irons SL, Pink RC, Carter DR, Kadhim M. 2012. Possible role of exosomes containing RNA in mediating nontargeted effect of ionizing radiation. Radiat Res. 177(5):539–545.
  • Alper T. 1977. The role of membrane damage in radiation-induced cell death. Adv Exp Med Biol. 84:139–165.
  • Ariazi J, Benowitz A, De Biasi V, Den Boer ML, Cherqui S, Cui H, Douillet N, Eugenin EA, Favre D, Goodman S, et al. 2017. Tunneling nanotubes and gap junctions-their role in long-range intercellular communication during development, health, and disease conditions. Front Mol Neurosci. 10:333.
  • Ariyoshi K, Miura T, Kasai K, Fujishima Y, Nakata A, Yoshida M. 2019. Radiation-induced bystander effect is mediated by mitochondrial DNA in exosome-like vesicles. Sci Rep. 9(1):9103.
  • Asur R, Butterworth KT, Penagaricano JA, Prise KM, Griffin RJ. 2015. High dose bystander effects in spatially fractionated radiation therapy. Cancer Lett. 356(1):52–57.
  • Asur RS, Sharma S, Chang CW, Penagaricano J, Kommuru IM, Moros EG, Corry PM, Griffin RJ. 2012. Spatially fractionated radiation induces cytotoxicity and changes in gene expression in bystander and radiation adjacent murine carcinoma cells. Radiat Res. 177(6):751–765.
  • Auerbach C. 1947. The induction by mustard gas of chromosomal instabilities in Drosophila melanogaster. Proc R Soc Edinb Biol. 62:307–320.
  • Autsavapromporn N, De Toledo SM, Buonanno M, Jay-Gerin JP, Harris AL, Azzam EI. 2011. Intercellular communication amplifies stressful effects in high-charge, high-energy (HZE) particle-irradiated human cells. J Radiat Res. 52(4):408–414.
  • Autsavapromporn N, Plante I, Liu C, Konishi T, Usami N, Funayama T, Azzam EI, Murakami T, Suzuki M. 2015. Genetic changes in progeny of bystander human fibroblasts after microbeam irradiation with X-rays, protons or carbon ions: the relevance to cancer risk. Int J Radiat Biol. 91(1):62–70.
  • Autsavapromporn N, Suzuki M, Funayama T, Usami N, Plante I, Yokota Y, Mutou Y, Ikeda H, Kobayashi K, Kobayashi Y, et al. 2013. Gap junction communication and the propagation of bystander effects induced by microbeam irradiation in human fibroblast cultures: the impact of radiation quality. Radiat Res. 180(4):367–375.
  • 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):497–504.
  • Azzam EI, de Toledo SM, Harris AL, Ivanov V, Zhou S, Amundson S, Lieberman H, Hei TH. 2013. The ionizing radiation-induced bystander effect: evidence, mechanism and significance. In: Sonis S, Keefe D, editors. Pathobiology of cancer regimen-related toxicities. New York, NY: Springer. p. 42–68. https://doi.org/10.1007/978-1-4614-5438-0_3
  • 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.
  • Azzam EI, de Toledo SM, Little JB. 2003a. Expression of CONNEXIN43 is highly sensitive to ionizing radiation and other environmental stresses. Cancer Res. 63(21):7128–7135.
  • Azzam EI, de Toledo SM, Little JB. 2003b. Oxidative metabolism, gap junctions and the ionizing radiation-induced bystander effect. Oncogene. 22(45):7050–7057.
  • Azzam EI, de Toledo SM, Spitz DR, Little JB. 2002. Oxidative metabolism modulates signal transduction and micronucleus formation in bystander cells from alpha-particle-irradiated normal human fibroblast cultures. Cancer Res. 62(19):5436–5442.
  • Azzam EI, Jay-Gerin JP, Pain D. 2012. Ionizing radiation-induced metabolic oxidative stress and prolonged cell injury. Cancer Lett. 327(1–2):48–60.
  • Balduzzi M, Sapora O, Matteucci A, Paradisi S. 2010. Modulation of the bystander effects induced by soluble factors in HaCaT cells by different exposure strategies. Radiat Res. 173(6):779–788.
  • Barendsen GW. 1994. The relationships between RBE and LET for different types of lethal damage in mammalian cells: biophysical and molecular mechanisms. Radiat Res. 139(3):257–270.
  • Baulch JE. 2019. Radiation-induced genomic instability, epigenetic mechanisms and the mitochondria: a dysfunctional ménage a trois? Int J Radiat Biol. 95(4):516–525.
  • Bedford JS, Dewey WC. 2002. Historical and current highlights in radiation biology: has anything important been learned by irradiating cells? Radiat Res. 158(3):251–291.
  • Belyakov OV, Folkard M, Mothersill C, Prise KM, Michael BD. 2002. Bystander-induced apoptosis and premature differentiation in primary urothelial explants after charged particle microbeam irradiation. Radiat Prot Dosimetry. 99(1–4):249–251.
  • Bergonié J, Tribondeau L. 2003. Interpretation of some results from radiotherapy and an attempt to determine a rational treatment technique. 1906. Yale J Biol Med. 76:181–182.
  • Bertucci A, Pocock RD, Randers-Pehrson G, Brenner DJ. 2009. Microbeam irradiation of the C. elegans nematode. J Radiat Res. 50(Suppl. A):A49–A54.
  • Bishayee A, Rao DV, Howell RW. 1999. Evidence for pronounced bystander effects caused by nonuniform distributions of radioactivity using a novel three-dimensional tissue culture model. Radiat Res. 152(1):88–97.
  • Blakely EA. 2000. Biological effects of cosmic radiation: deterministic and stochastic. Health Phys. 79(5):495–506.
  • Brenner DJ, Little JB, Sachs RK. 2001. The bystander effect in radiation oncogenesis: II. A quantitative model. Radiat Res. 155(3):402–408.
  • Brenner DJ, Sachs RK. 2002. Do low dose-rate bystander effects influence domestic radon risks? Int J Radiat Biol. 78(7):593–604.
  • Brenner DJ, Sachs RK. 2003. Domestic radon risks may be dominated by bystander effects—but the risks are unlikely to be greater than we thought. Health Phys. 85(1):103–108.
  • Brooks AL, Retherford JC, McClellan RO. 1974. Effect of 239PuO2 particle number and size on the frequency and distribution of chromosome aberrations in the liver of the Chinese hamster. Radiat Res. 59(3):693–709.
  • Buonanno M, de Toledo SM, Azzam EI. 2011. Increased frequency of spontaneous neoplastic transformation in progeny of bystander cells from cultures exposed to densely ionizing radiation. PLOS One. 6(6):e21540.
  • Buonanno M, de Toledo SM, Howell RW, Azzam EI. 2015. Low-dose energetic protons induce adaptive and bystander effects that protect human cells against DNA damage caused by a subsequent exposure to energetic iron ions. J Radiat Res. 56(3):502–508.
  • Buonanno M, de Toledo SM, Pain D, Azzam EI. 2011. Long-term consequences of radiation-induced bystander effects depend on radiation quality and dose and correlate with oxidative stress. Radiat Res. 175(4):405–415.
  • Buonanno M, Randers-Pehrson G, Smilenov LB, Kleiman NJ, Young E, Ponnayia B, Brenner DJ. 2015. A mouse ear model for bystander studies induced by microbeam irradiation. Radiat Res. 184(2):219–225.
  • Burdak-Rothkamm S, Rothkamm K, Prise KM. 2008. ATM acts downstream of ATR in the DNA damage response signaling of bystander cells. Cancer Res. 68(17):7059–7065.
  • Butterworth KT, McGarry CK, Trainor C, O'Sullivan JM, Hounsell AR, Prise KM. 2011. Out-of-field cell survival following exposure to intensity-modulated radiation fields. Int J Radiat Oncol Biol Phys. 79(5):1516–1522.
  • Cagatay T, Mayah S, Mancuso A, Giardullo M, Pazzaglia P, Saran S, Daniel A, Traynor A, Meade D, Lyng AD, et al. 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. 21:8389.
  • Cai S, Shi GS, Cheng HY, Zeng YN, Li G, Zhang M, Song M, Zhou PK, Tian Y, Cui FM, et al. 2017. Exosomal miR-7 mediates bystander autophagy in lung after focal brain irradiation in mice. Int J Biol Sci. 13(10):1287–1296.
  • Canter BS, Leung CN, Fritton JC, Bäck T, Rajon D, Azzam EI, Howell RW. 2021. Radium-223-induced bystander effects cause DNA damage and apoptosis in disseminated tumor cells in bone marrow. Mol Cancer Res. 19(10):1739–1750.
  • Chai Y, Calaf GM, Zhou H, Ghandhi SA, Elliston CD, Wen G, Nohmi T, Amundson SA, Hei TK. 2013. Radiation induced COX-2 expression and mutagenesis at non-targeted lung tissues of gpt delta transgenic mice. Br J Cancer. 108(1):91–98.
  • Chang WP, Little JB. 1992. Persistently elevated frequency of spontaneous mutations in progeny of CHO clones surviving X-irradiation: association with delayed reproductive death phenotype. Mutat Res. 270(2):191–199.
  • Colangelo NW, Azzam EI. 2020. Extracellular vesicles originating from glioblastoma cells increase metalloproteinase release by astrocytes: the role of CD147 (EMMPRIN) and ionizing radiation. Cell Commun Signal. 18(1):21.
  • Constanzo J, Faget J, Ursino C, Badie C, Pouget JP. 2021. Radiation-induced immunity and toxicities: the versatility of the cGAS-STING pathway. Front Immunol. 12:680503.
  • Cucinotta FA, Nikjoo H, Goodhead DT. 1998. The effects of delta rays on the number of particle-track traversals per cell in laboratory and space exposures. Radiat Res. 150(1):115–119.
  • de Toledo SM, Buonanno M, Harris AL, Azzam EI. 2017. Genomic instability induced in distant progeny of bystander cells depends on the connexins expressed in the irradiated cells. Int J Radiat Biol. 93(10):1182–1194.
  • 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.
  • Desai S, Kobayashi A, Konishi T, Oikawa M, Pandey BN. 2014. Damaging and protective bystander cross-talk between human lung cancer and normal cells after proton microbeam irradiation. Mutat Res. 763–764:39–44.
  • Desai S, Kumar A, Laskar S, Pandey BN. 2013. Cytokine profile of conditioned medium from human tumor cell lines after acute and fractionated doses of gamma radiation and its effect on survival of bystander tumor cells. Cytokine. 61(1):54–62.
  • Desai S, Srambikkal N, Yadav HD, Shetake N, Balla MM, Kumar A, Ray P, Ghosh A, Pandey BN. 2016. Molecular understanding of growth inhibitory effect from irradiated to bystander tumor cells in mouse fibrosarcoma tumor model. PLOS One. 11(8):e0161662.
  • Deshpande A, Goodwin EH, Bailey SM, Marrone BL, Lehnert BE. 1996. Alpha-particle-induced sister chromatid exchange in normal human lung fibroblasts: evidence for an extranuclear target. Radiat Res. 145(3):260–267.
  • Devhare PB, Ray RB. 2018. Extracellular vesicles: novel mediator for cell to cell communications in liver pathogenesis. Mol Aspects Med. 60:115–122.
  • Dilmanian FA, Qu Y, Feinendegen LE, Pena LA, Bacarian T, Henn FA, Kalef-Ezra J, Liu S, Zhong Z, McDonald JW. 2007. Tissue-sparing effect of X-ray microplanar beams particularly in the CNS: is a bystander effect involved? Exp Hematol. 35(4 Suppl. 1):69–77.
  • Durante M, Brenner DJ, Formenti SC. 2016. Does heavy ion therapy work through the immune system? Int J Radiat Oncol Biol Phys. 96(5):934–936.
  • Emerit I, Oganesian N, Sarkisian T, Arutyunyan R, Pogosian A, Asrian K, Levy A, Cernjavski L. 1995. Clastogenic factors in the plasma of Chernobyl accident recovery workers: anticlastogenic effect of Ginkgo biloba extract. Radiat Res. 144(2):198–205.
  • Failla G. 1921. Dosage in radium therapy. Am J Roentgenol. 8:674–685.
  • Failla G. 1926. The question of a biologic unit of radiation. Acta Radiol. 6(1–6):413–439.
  • Folkard M, Schettino G, Vojnovic B, Gilchrist S, Michette AG, Pfauntsch SJ, Prise KM, Michael BD. 2001. A focused ultrasoft X-ray microbeam for targeting cells individually with submicrometer accuracy. Radiat Res. 156(6):796–804.
  • Frankenberg D, Greif KD, Giesen U. 2006. Radiation response of primary human skin fibroblasts and their bystander cells after exposure to counted particles at low and high LET. Int J Radiat Biol. 82(1):59–67.
  • Friedman DL, Whitton J, Leisenring W, Mertens AC, Hammond S, Stovall M, Donaldson SS, Meadows AT, Robison LL, Neglia JP. 2010. Subsequent neoplasms in 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst. 102(14):1083–1095.
  • Gaillard S, Pusset D, de Toledo SM, Fromm M, Azzam EI. 2009. Propagation distance of the alpha-particle-induced bystander effect: the role of nuclear traversal and gap junction communication. Radiat Res. 171(5):513–520.
  • Gao Y, Ma H, Lv C, Lan F, Wang Y, Deng Y. 2021. Exosomes and exosomal microRNA in non-targeted radiation bystander and abscopal effects in the central nervous system. Cancer Lett. 499:73–84.
  • Gerashchenko BI, Howell RW. 2003. Cell proximity is a prerequisite for the proliferative response of bystander cells co-cultured with cells irradiated with gamma-rays. Cytometry A. 56(2):71–80.
  • Goh K, Sumner H. 1968. Breaks in normal human chromosomes: are they induced by a transferable substance in the plasma of persons exposed to total-body irradiation? Radiat Res. 35(1):171–181.
  • Golden EB, Apetoh L. 2015. Radiotherapy and immunogenic cell death. Semin Radiat Oncol. 25(1):11–17.
  • Golden EB, Chhabra A, Chachoua A, Adams S, Donach M, Fenton-Kerimian M, Friedman K, Ponzo F, Babb JS, Goldberg J, et al. 2015. Local radiotherapy and granulocyte-macrophage colony-stimulating factor to generate abscopal responses in patients with metastatic solid tumours: a proof-of-principle trial. Lancet Oncol. 16(7):795–803.
  • Golden EB, Frances D, Pellicciotta I, Demaria S, Barcellos-Hoff MH, Formenti SC. 2014. Radiation fosters dose-dependent and chemotherapy-induced immunogenic cell death. Oncoimmunology. 3:e28518.
  • Gonon G, Groetz JE, de Toledo SM, Howell RW, Fromm M, Azzam EI. 2013. Nontargeted stressful effects in normal human fibroblast cultures exposed to low fluences of high charge, high energy (HZE) particles: kinetics of biologic responses and significance of secondary radiations. Radiat Res. 179(4):444–457.
  • Goodenough DA, Goliger JA, Paul DL. 1996. Connexins, connexons, and intercellular communication. Annu Rev Biochem. 65:475–502.
  • Goodhead DT, Nikjoo H. 1989. Track structure analysis of ultrasoft X-rays compared to high- and low-LET radiations. Int J Radiat Biol. 55(4):513–529.
  • Gow MD, Seymour CB, Ryan LA, Mothersill CE. 2010. Induction of bystander response in human glioma cells using high-energy electrons: a role for TGF-beta1. Radiat Res. 173(6):769–778.
  • Grass GD, Krishna N, Kim S. 2016. The immune mechanisms of abscopal effect in radiation therapy. Curr Probl Cancer. 40(1):10–24.
  • Griffin RJ, Prise KM, McMahon SJ, Zhang X, Penagaricano J, Butterworth KT. 2020. History and current perspectives on the biological effects of high-dose spatial fractionation and high dose-rate approaches: GRID, microbeam & FLASH radiotherapy. Br J Radiol. 93(1113):20200217.
  • Grosovsky AJ, Parks KK, Giver CR, Nelson SL. 1996. Clonal analysis of delayed karyotypic abnormalities and gene mutations in radiation-induced genetic instability. Mol Cell Biol. 16(11):6252–6262.
  • Hamada N, Ni M, Funayama T, Sakashita T, Kobayashi Y. 2008. Temporally distinct response of irradiated normal human fibroblasts and their bystander cells to energetic heavy ions. Mutat Res. 639(1–2):35–44.
  • Han W, Chen S, Yu KN, Wu L. 2010. Nitric oxide mediated DNA double strand breaks induced in proliferating bystander cells after alpha-particle irradiation. Mutat Res. 684(1–2):81–89.
  • Hanahan D, Weinberg RA. 2011. Hallmarks of cancer: the next generation. Cell. 144(5):646–674.
  • Harper K, Lorimore SA, Wright EG. 1997. Delayed appearance of radiation-induced mutations at the Hprt locus in murine hemopoietic cells. Exp Hematol. 25(3):263–269.
  • Harris AL. 2007. Connexin channel permeability to cytoplasmic molecules. Prog Biophys Mol Biol. 94(1–2):120–143.
  • Harris AL. 2018. Electrical coupling and its channels. J Gen Physiol. 150(12):1606–1639.
  • He C, Li L, Wang L, Meng W, Hao Y, Zhu G. 2021. Exosome-mediated cellular crosstalk within the tumor microenvironment upon irradiation. Cancer Biol Med. 18(1):21–33.
  • He M, Dong C, Xie Y, Li J, Yuan D, Bai Y, Shao C. 2014. Reciprocal bystander effect between α-irradiated macrophage and hepatocyte is mediated by cAMP through a membrane signaling pathway. Mutat Res. 763–764:1–9.
  • Heeran AB, Berrigan HP, O'Sullivan J. 2019. The radiation-induced bystander effect (RIBE) and its connections with the hallmarks of cancer. Radiat Res. 192(6):668–679.
  • Held KD. 2009. Effects of low fluences of radiations found in space on cellular systems. Int J Radiat Biol. 85(5):379–390.
  • 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.
  • Holmberg K, Meijer AE, Auer G, Lambert BO. 1995. Delayed chromosomal instability in human T-lymphocyte clones exposed to ionizing radiation. Int J Radiat Biol. 68(3):245–255.
  • Hong X, Sin WC, Harris AL, Naus CC. 2015. Gap junctions modulate glioma invasion by direct transfer of microRNA. Oncotarget. 6(17):15566–15577.
  • Hoorelbeke D, Decrock E, De Smet M, De Bock M, Descamps B, Van Haver V, Delvaeye T, Krysko DV, Vanhove C, Bultynck G, et al. 2020. Cx43 channels and signaling via IP3/Ca2+, ATP, and ROS/NO propagate radiation-induced DNA damage to non-irradiated brain microvascular endothelial cells. Cell Death Dis. 11:194.
  • Hu B, Grabham P, Nie J, Balajee AS, Zhou H, Hei TK, Geard CR. 2012. Intrachromosomal changes and genomic instability in site-specific microbeam-irradiated and bystander human-hamster hybrid cells. Radiat Res. 177(1):25–34.
  • Hu W, Xu S, Yao B, Hong M, Wu X, Pei H, Chang L, Ding N, Gao X, Ye C, et al. 2014. MiR-663 inhibits radiation-induced bystander effects by targeting TGFB1 in a feedback mode. RNA Biol. 11(9):1189–1198.
  • Huo L, Nagasawa H, Little JB. 2001. HPRT mutants induced in bystander cells by very low fluences of alpha particles result primarily from point mutations. Radiat Res. 156(5 Pt 1):521–525.
  • Ivanov VN, Zhou NH, Ghandhi SA, Karasic TB, Yaghoubian B, Amundson SA, Hei TK. 2010. Radiation-induced bystander signaling pathways in human fibroblasts: a role for interleukin-33 in the signal transmission. Cell Signal. 22(7):1076–1087.
  • Iyer R, Lehnert BE, Svensson R. 2000. Factors underlying the cell growth-related bystander responses to alpha particles. Cancer Res. 60(5):1290–1298.
  • Jain MR, Li ML, Chen W, Liu T, de Toledo SM, Pandey BN, Li H, Rabin BM, Azzam EI. 2011. In vivo space radiation-induced non-targeted responses: late effects on molecular signaling in mitochondria. Curr Mol Pharmacol. 4(2):106–114.
  • 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.
  • Jelonek K, Widlak P, Pietrowska M. 2016. The influence of ionizing radiation on exosome composition, secretion and intercellular communication. Protein Pept Lett. 23(7):656–663.
  • Jesenko T, Bosnjak M, Markelc B, Sersa G, Znidar K, Heller L, Cemazar M. 2020. Radiation induced upregulation of DNA sensing pathways is cell-type dependent and can mediate the off-target effects. Cancers. 12(11):3365.
  • 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.
  • Kanagavelu S, Gupta S, Wu X, Philip S, Wattenberg MM, Hodge JW, Couto MD, Chung KD, Ahmed MM. 2014. In vivo effects of lattice radiation therapy on local and distant lung cancer: potential role of immunomodulation. Radiat Res. 182(2):149–162.
  • Khan MA, Hill RP, Van Dyk J. 1998. Partial volume rat lung irradiation: an evaluation of early DNA damage. Int J Radiat Oncol Biol Phys. 40(2):467–476.
  • Kobayashi Y, Funayama T, Hamada N, Sakashita T, Konishi T, Imaseki H, Yasuda K, Hatashita M, Takagi K, Hatori S, et al. 2009. Microbeam irradiation facilities for radiobiology in Japan and China. J Radiat Res. 50(Suppl. A):A29–A47.
  • Kong EY, Cheng SH, Yu KN. 2018. Induction of autophagy and interleukin 6 secretion in bystander cells: metabolic cooperation for radiation-induced rescue effect? J Radiat Res. 59(2):129–140.
  • Koturbash I, Loree J, Kutanzi K, Koganow C, Pogribny I, Kovalchuk O. 2008. In vivo bystander effect: cranial X-irradiation leads to elevated DNA damage, altered cellular proliferation and apoptosis, and increased p53 levels in shielded spleen. Int J Radiat Oncol Biol Phys. 70(2):554–562.
  • Kovalchuk A, Mychasiuk R, Muhammad A, Hossain S, Ilnytskyy S, Ghose A, Kirkby C, Ghasroddashti E, Kovalchuk O, Kolb B. 2016. Liver irradiation causes distal bystander effects in the rat brain and affects animal behaviour. Oncotarget. 7(4):4385–4398.
  • Kronenberg A. 1994. Radiation-induced genomic instability. Int J Radiat Biol. 66(5):603–609.
  • Laiakis EC, Strassburg K, Bogumil R, Lai S, Vreeken RJ, Hankemeier T, Langridge J, Plumb RS, Fornace AJ Jr, Astarita G. 2014. Metabolic phenotyping reveals a lipid mediator response to ionizing radiation. J Proteome Res. 13(9):4143–4154.
  • Lampe PD, Lau AF. 2004. The effects of connexin phosphorylation on gap junctional communication. Int J Biochem Cell Biol. 36(7):1171–1186.
  • Lea DE. 1947. Actions of radiations of living cells. Cambridge (UK); New York: University Press; The Macmillan Company; p. 402.
  • Lehnert BE, Goodwin EH, Deshpande A. 1997. Extracellular factor(s) following exposure to alpha particles can cause sister chromatid exchanges in normal human cells. Cancer Res. 57(11):2164–2171.
  • Leung CN, Canter BS, Rajon D, Bäck TA, Fritton JC, Azzam EI, Howell RW. 2020. Dose-dependent growth delay of breast cancer xenografts in the bone marrow of mice treated with 223Ra: the role of bystander effects and their potential for therapy. J Nucl Med. 61(1):89–95.
  • Little JB, Gorgojo L, Vetrovs H. 1990. Delayed appearance of lethal and specific gene mutations in irradiated mammalian cells. Int J Radiat Oncol Biol Phys. 19(6):1425–1429.
  • Little JB, Nagasawa H, Li GC, Chen DJ. 2003. Involvement of the nonhomologous end joining DNA repair pathway in the bystander effect for chromosomal aberrations. Radiat Res. 159(2):262–267.
  • Little JB, Nagasawa H, Pfenning T, Vetrovs H. 1997. Radiation-induced genomic instability: delayed mutagenic and cytogenetic effects of X rays and alpha particles. Radiat Res. 148(4):299–307.
  • Little JB. 2003. Genomic instability and bystander effects: a historical perspective. Oncogene. 22(45):6978–6987.
  • Liu Z, Mothersill CE, McNeill FE, Lyng FM, Byun SH, Seymour CB, Prestwich WV. 2006. A dose threshold for a medium transfer bystander effect for a human skin cell line. Radiat Res. 166(1 Pt 1):19–23.
  • Lorimore SA, Coates PJ, Scobie GE, Milne G, Wright EG. 2001. Inflammatory-type responses after exposure to ionizing radiation in vivo: a mechanism for radiation-induced bystander effects? Oncogene. 20(48):7085–7095.
  • Lyng FM, Maguire P, McClean B, Seymour CB, Mothersill CE. 2006. The involvement of calcium and MAP kinase signaling pathways in the production of radiation-induced bystander effects. Radiat Res. 165(4):400–409.
  • Lyng FM, Seymour CB, Mothersill CE. 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.
  • Maguire P, Mothersill CE, Seymour CB, Lyng FM. 2005. Medium from irradiated cells induces dose-dependent mitochondrial changes and BCL2 responses in unirradiated human keratinocytes. Radiat Res. 163(4):384–390.
  • Malloci M, Perdomo L, Veerasamy M, Andriantsitohaina R, Simard G, Martínez MC. 2019. Extracellular vesicles: mechanisms in human health and disease. Antioxid Redox Signal. 30(6):813–856.
  • Mancuso M, Pasquali E, Leonardi S, Rebessi S, Tanori M, Giardullo P, Borra F, Pazzaglia S, Naus CC, Di Majo V, et al. 2011. Role of connexin43 and ATP in long-range bystander radiation damage and oncogenesis in vivo. Oncogene. 30(45):4601–4608.
  • Mancuso M, Pasquali E, Leonardi S, Tanori M, Rebessi S, Di Majo V, Pazzaglia S, Toni MP, Pimpinella M, Covelli V, et al. 2008. Oncogenic bystander radiation effects in patched heterozygous mouse cerebellum. Proc Natl Acad Sci U S A. 105(34):12445–12450.
  • Mansell E, Zareian N, Malouf C, Kapeni C, Brown N, Badie C, Baird D, Lane J, Ottersbach K, Blair A, et al. 2019. DNA damage signalling from the placenta to foetal blood as a potential mechanism for childhood leukaemia initiation. Sci Rep. 9(1):4370.
  • Mariotti LG, Bertolotti A, Ranza E, Babini G, Ottolenghi A. 2012. Investigation of the mechanisms underpinning IL-6 cytokine release in bystander responses: the roles of radiation dose, radiation quality and specific ROS/RNS scavengers. Int J Radiat Biol. 88(10):751–762.
  • Matejka N, Reindl J. 2020. Influence of α-particle radiation on intercellular communication networks of tunneling nanotubes in U87 glioblastoma cells. Front Oncol. 10:1691.
  • Menezes ME, Bhatia S, Bhoopathi P, Das SK, Emdad L, Dasgupta S, Dent P, Wang XY, Sarkar D, Fisher PB. 2014. MDA-7/IL-24: multifunctional cancer killing cytokine. Adv Exp Med Biol. 818:127–153.
  • Meşe G, Richard G, White TW. 2007. Gap junctions: basic structure and function. J Invest Dermatol. 127(11):2516–2524.
  • Metting NF, Rossi HH, Braby LA, Kliauga PJ, Howard J, Zaider M, Schimmerling W, Wong M, Rapkin M. 1988. Microdosimetry near the trajectory of high-energy heavy ions. Radiat Res. 116(2):183–195.
  • Mitchell SA, Randers-Pehrson G, Brenner DJ, Hall EJ. 2004. The bystander response in C3H 10T1/2 cells: the influence of cell-to-cell contact. Radiat Res. 161(4):397–401.
  • Mo LJ, Song M, Huang QH, Guan H, Liu XD, Xie DF, Huang B, Huang RX, Zhou PK. 2018. Exosome-packaged miR-1246 contributes to bystander DNA damage by targeting LIG4. Br J Cancer. 119(4):492–502.
  • Morgan WF. 2003a. Non-targeted and delayed effects of exposure to ionizing radiation: I. Radiation-induced genomic instability and bystander effects in vitro. Radiat Res. 159(5):567–580.
  • Morgan WF. 2003b. 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):581–596.
  • Mothersill CE, Rusin A, Fernandez-Palomo C, Seymour CB. 2018. History of bystander effects research 1905-present; what is in a name? Int J Radiat Biol. 94(8):696–707.
  • Mothersill CE, Seymour CB. 1997. Medium from irradiated human epithelial cells but not human fibroblasts reduces the clonogenic survival of unirradiated cells. Int J Radiat Biol. 71:421–427.
  • Munro TR. 1970. The relative radiosensitivity of the nucleus and cytoplasm of Chinese hamster fibroblasts. Radiat Res. 42(3):451–470.
  • Murphy JB, Morton JJ. 1915. The effect of Roentgen rays on the rate of growth of spontaneous tumors in mice. J Exp Med. 22(6):800–803.
  • Nagasawa H, Huo L, Little JB. 2003. Increased bystander mutagenic effect in DNA double-strand break repair-deficient mammalian cells. Int J Radiat Biol. 79(1):35–41.
  • Nagasawa H, Little JB. 1992. Induction of sister chromatid exchanges by extremely low doses of alpha-particles. Cancer Res. 52(22):6394–6396.
  • Nakaoka A, Nakahana M, Inubushi S, Akasaka H, Salah M, Fujita Y, Kubota H, Hassan M, Nishikawa R, Mukumoto N, et al. 2021. Exosome-mediated radiosensitizing effect on neighboring cancer cells via increase in intracellular levels of reactive oxygen species. Oncol Rep. 45(4):13.
  • Narayanan PK, Goodwin EH, Lehnert BE. 1997. Alpha particles initiate biological production of superoxide anions and hydrogen peroxide in human cells. Cancer Res. 57(18):3963–3971.
  • National Research Council. 2008. Managing space radiation risk in the new era of space exploration. In: National Research Council, National Academies (U.S.A). Committee on the Evaluation of Radiation Shielding for Space Exploration, editor. Vol. xiii. Washington (DC): National Academies Press; p. 117.
  • National Council on Radiation Protection and Measurements (NCRP). 2020. Approaches for integrating information from radiation biology and epidemiology to enhance low-dose health risk assessment: recommendations of the National Council on Radiation Protection and Measurements. In: Scientific Committee 1–26 of the NCRP, editors. NCRP report no. 186, 1 online resource. Bethesda (MD): National Council on Radiation Protection and Measurements.
  • Newcombe HB, Scott GW. 1949. Factors responsible for the delayed appearance of radiation-induced mutants in Escherichia coli. Genetics. 34(5):475–492.
  • Newhauser WD, Durante M. 2011. Assessing the risk of second malignancies after modern radiotherapy. Nat Rev Cancer. 11(6):438–448.
  • Niessen H, Harz H, Bedner P, Kramer K, Willecke K. 2000. Selective permeability of different connexin channels to the second messenger inositol 1,4,5-trisphosphate. J Cell Sci. 113(8):1365–1372.
  • Ochoa de Olza M, Bourhis J, Irving M, Coukos G, Herrera FG. 2020. High versus low dose irradiation for tumor immune reprogramming. Curr Opin Biotechnol. 65:268–283.
  • Ohba K, Omagari K, Nakamura T, Ikuno N, Saeki S, Matsuo I, Kinoshita H, Masuda J, Hazama H, Sakamoto I, et al. 1998. Abscopal regression of hepatocellular carcinoma after radiotherapy for bone metastasis. Gut. 43(4):575–577.
  • Ohshima Y, Tsukimoto M, Harada H, Kojima S. 2012. Involvement of connexin43 hemichannel in ATP release after γ-irradiation. J Radiat Res. 53(4):551–557.
  • Pampfer S, Streffer C. 1989. Increased chromosome aberration levels in cells from mouse fetuses after zygote X-irradiation. Int J Radiat Biol. 55(1):85–92.
  • Pant GS, Kamada N. 1977. Chromosome aberrations in normal leukocytes induced by the plasma of exposed individuals. Hiroshima J Med Sci. 26(2–3):149–154.
  • Patheja P, Dasgupta R, Dube A, Ahlawat S, Verma RS, Gupta PK. 2015. The use of optical trap and microbeam to investigate the mechanical and transport characteristics of tunneling nanotubes in tumor spheroids. J Biophotonics. 8(9):694–704.
  • Patheja P, Sahu K. 2017. Macrophage conditioned medium induced cellular network formation in MCF-7 cells through enhanced tunneling nanotube formation and tunneling nanotube mediated release of viable cytoplasmic fragments. Exp Cell Res. 355(2):182–193.
  • Peng Y, Wang X, Guo Y, Peng F, Zheng N, He B, Ge H, Tao L, Wang Q. 2019. Pattern of cell-to-cell transfer of microRNA by gap junction and its effect on the proliferation of glioma cells. Cancer Sci. 110(6):1947–1958.
  • Penuela S, Gehi R, Laird DW. 2013. The biochemistry and function of pannexin channels. Biochim Biophys Acta. 1828(1):15–22.
  • Persaud R, Zhou H, Baker SE, Hei TK, Hall EJ. 2005. Assessment of low linear energy transfer radiation-induced bystander mutagenesis in a three-dimensional culture model. Cancer Res. 65(21):9876–9882.
  • Petkau A. 1980. Radiation carcinogenesis from a membrane perspective. Acta Physiol Scand Suppl. 492:81–90.
  • Ponnaiya B, Jenkins-Baker G, Brenner DJ, Hall EJ, Randers-Pehrson G, Geard CR. 2004. Biological responses in known bystander cells relative to known microbeam-irradiated cells. Radiat Res. 162(4):426–432.
  • 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.
  • Pouget JP, Georgakilas AG, Ravanat JL. 2018. Targeted and off-target (bystander and abscopal) effects of radiation therapy: redox mechanisms and risk/benefit analysis. Antioxid Redox Signal. 29(15):1447–1487.
  • Prezado Y, Jouvion G, Patriarca A, Nauraye C, Guardiola C, Juchaux M, Lamirault C, Labiod D, Jourdain L, Sebrie C, et al. 2018. Proton minibeam radiation therapy widens the therapeutic index for high-grade gliomas. Sci Rep. 8(1):16479.
  • Prise KM, Belyakov OV, Folkard M, Michael BD. 1998. Studies of bystander effects in human fibroblasts using a charged particle microbeam. Int J Radiat Biol. 74(6):793–798.
  • Prise KM, O'Sullivan JM. 2009. Radiation-induced bystander signalling in cancer therapy. Nat Rev Cancer. 9(5):351–360.
  • Rajan V, Pandey BN. 2021. Cytoproliferative effect of low dose alpha radiation in human lung cancer cells is associated with connexin 43, caveolin-1, and survivin pathway. Int J Radiat Biol. 97(3):356–366.
  • Randers-Pehrson G, Geard CR, Johnson G, Elliston CD, Brenner DJ. 2001. The Columbia University single-ion microbeam. Radiat Res. 156(2):210–214.
  • Regaud C, Ferroux R. 1927. Discordance des effects de rayons X, d’une part dans le testicile, par le peau, d’autre parts dans le fractionment de la dose. Compt Rend Soc Biol. 97:431–434.
  • Reynders K, Illidge T, Siva S, Chang JY, De Ruysscher D. 2015. The abscopal effect of local radiotherapy: using immunotherapy to make a rare event clinically relevant. Cancer Treat Rev. 41(6):503–510.
  • Rodriguez-Ruiz ME, Vanpouille-Box C, Melero I, Formenti SC, Demaria S. 2018. Immunological mechanisms responsible for radiation-induced abscopal effect. Trends Immunol. 39(8):644–655.
  • Rustom A, Saffrich R, Markovic I, Walther P, Gerdes HH. 2004. Nanotubular highways for intercellular organelle transport. Science. 303(5660):1007–1010.
  • Sabatier L, Dutrillaux B, Martin MB. 1992. Chromosomal instability. Nature. 357(6379):548.
  • Sawant SG, Randers-Pehrson G, Geard CR, Brenner DJ, Hall EJ. 2001. The bystander effect in radiation oncogenesis: I. Transformation in C3H 10T1/2 cells in vitro can be initiated in the unirradiated neighbors of irradiated cells. Radiat Res. 155(3):397–401.
  • Schettino G, Folkard M, Prise KM, Vojnovic B, Michael BD. 2002. Upgrading of the Gray Laboratory soft X ray microprobe and V79 survival measurements following irradiation of one or all cells with a CK X ray beam of different size. Radiat Prot Dosimetry. 99(1):287–288.
  • Shao C, Aoki M, Furusawa Y. 2003. Bystander effect on cell growth stimulation in neoplastic HSGc cells induced by heavy-ion irradiation. Radiat Environ Biophys. 42(3):183–187.
  • Shao C, Folkard M, Michael BD, Prise KM. 2004. Targeted cytoplasmic irradiation induces bystander responses. Proc Natl Acad Sci USA. 101(37):13495–13500.
  • Shao C, Folkard M, Prise KM. 2008. Role of TGF-beta1 and nitric oxide in the bystander response of irradiated glioma cells. Oncogene. 27(4):434–440.
  • Shao C, Furusawa Y, Kobayashi Y, Funayama T, Wada S. 2003. Bystander effect induced by counted high-LET particles in confluent human fibroblasts: a mechanistic study. FASEB J. 17(11):1422–1427.
  • Shao C, Stewart V, Folkard M, Michael BD, Prise KM. 2003. Nitric oxide-mediated signaling in the bystander response of individually targeted glioma cells. Cancer Res. 63:8437–8442.
  • Song M, Wang Y, Shang ZF, Liu XD, Xie DF, Wang Q, Guan H, Zhou PK. 2016. Bystander autophagy mediated by radiation-induced exosomal miR-7-5p in non-targeted human bronchial epithelial cells. Sci Rep. 6:30165.
  • Song Y, Hu S, Zhang J, Zhu L, Zhao X, Chen Q, Bai Y, Pan Y, Shao C. 2021. Fractionated irradiation of right thorax induces abscopal damage on bone marrow cells via TNF-α and SAA. Int J Mol Sci. 22:9964.
  • Spitz DR, Azzam EI, Li JJ, Gius D. 2004. Metabolic oxidation/reduction reactions and cellular responses to ionizing radiation: a unifying concept in stress response biology. Cancer Metastasis Rev. 23(3–4):311–322.
  • Stone HB, Peters LJ, Milas L. 1979. Effect of host immune capability on radiocurability and subsequent transplantability of a murine fibrosarcoma. J Natl Cancer Inst. 63(5):1229–1235.
  • Su Z, Emdad L, Sauane M, Lebedeva IV, Sarkar D, Gupta P, James CD, Randolph A, Valerie K, Walter MR, et al. 2005. Unique aspects of MDA-7/IL-24 antitumor bystander activity: establishing a role for secretion of MDA-7/IL-24 protein by normal cells. Oncogene. 24(51):7552–7566.
  • Suchowerska N, Ebert MA, Zhang M, Jackson M. 2005. In vitro response of tumour cells to non-uniform irradiation. Phys Med Biol. 50(13):3041–3051.
  • Sudo H, Garbe J, Stampfer MR, Barcellos-Hoff MH, Kronenberg A. 2008. Karyotypic instability and centrosome aberrations in the progeny of finite life-span human mammary epithelial cells exposed to sparsely or densely ionizing radiation. Radiat Res. 170(1):23–32.
  • Sugimoto T, Dazai K, Sakashita T, Funayama T, Wada S, Hamada N, Kakizaki T, Kobayashi Y, Higashitani A. 2006. Cell cycle arrest and apoptosis in Caenorhabditis elegans germline cells following heavy-ion microbeam irradiation. Int J Radiat Biol. 82(1):31–38.
  • Sui H, Goldberg S, Niemierko A, Ancukiewicz M, Hall E, Goitein M, Wong W, Paganetti H. 2007. Secondary carcinogenesis in patients treated with radiation: a review of data on radiation-induced cancers in human, non-human primate, canine and rodent subjects. Radiat Res. 167:12–42.
  • Suzuki M, Tsuruoka C. 2004. Heavy charged particles produce a bystander effect via cell–cell junctions. Biol Sci Space. 18(4):241–246.
  • Suzuki M, Yasuda N, Kitamura H. 2020. Lethal and mutagenic bystander effects in human fibroblast cell cultures subjected to low-energy-carbon ions. Int J Radiat Biol. 96(2):179–186.
  • Tamminga J, Kovalchuk O. 2011. Role of DNA damage and epigenetic DNA methylation changes in radiation-induced genomic instability and bystander effects in germline in vivo. Curr Mol Pharmacol. 4(2):115–125.
  • Terzaghi M, Little JB. 1976. X-radiation-induced transformation in a C3H mouse embryo-derived cell line. Cancer Res. 36:1367–1374.
  • Tomita M, Matsumoto H, Funayama T, Yokota Y, Otsuka K, Maeda M, Kobayashi Y. 2015. Nitric oxide-mediated bystander signal transduction induced by heavy-ion microbeam irradiation. Life Sci Space Res. 6:36–43.
  • Tubin S, Yan W, Mourad WF, Fossati P, Khan MK. 2020. The future of radiation-induced abscopal response: beyond conventional radiotherapy approaches. Future Oncol. 16(16):1137–1151.
  • Upham BL, Trosko JE. 2009. Oxidative-dependent integration of signal transduction with intercellular gap junctional communication in the control of gene expression. Antioxid Redox Signal. 11(2):297–307.
  • Usami N, Maeda M, Eguchi-Kasai K, Maezawa H, Kobayashi K. 2006. Radiation-induced gamma-H2AX in mammalian cells irradiated with a synchrotron X-ray microbeam. Radiat Prot Dosimetry. 122(1–4):307–309.
  • Wan C, Sun Y, Tian Y, Lu L, Dai X, Meng J, Huang J, He Q, Wu B, Zhang Z, et al. 2020. Irradiated tumor cell-derived microparticles mediate tumor eradication via cell killing and immune reprogramming. Sci Adv. 6(13):eaay9789.
  • Wang X, Veruki ML, Bukoreshtliev NV, Hartveit E, Gerdes HH. 2010. Animal cells connected by nanotubes can be electrically coupled through interposed gap-junction channels. Proc Natl Acad Sci USA. 107(40):17194–17199.
  • Ward JF. 1988. DNA damage produced by ionizing radiation in mammalian cells: identities, mechanisms of formation, and reparability. Prog Nucleic Acid Res Mol Biol. 35:95–125.
  • Watson GE, Pocock DA, Papworth D, Lorimore SA, Wright EG. 2001. In vivo chromosomal instability and transmissible aberrations in the progeny of haemopoietic stem cells induced by high- and low-LET radiations. Int J Radiat Biol. 77(4):409–417.
  • Wiese C, Pierce AJ, Gauny SS, Jasin M, Kronenberg A. 2002. Gene conversion is strongly induced in human cells by double-strand breaks and is modulated by the expression of BCL-x(L). Cancer Res. 62(5):1279–1283.
  • Wu C, Liu T, Chen W, Oka S-i, Fu C, Jain MR, Parrott AM, Baykal AT, Sadoshima J, Li H. 2010. Redox regulatory mechanism of transnitrosylation by thioredoxin. Mol Cell Proteomics. 9(10):2262–2275.
  • Wu LJ, Randers-Pehrson G, Xu A, Waldren CA, Geard CR, Yu Z, Hei TK. 1999. Targeted cytoplasmic irradiation with alpha particles induces mutations in mammalian cells. Proc Natl Acad Sci USA. 96(9):4959–4964.
  • 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.
  • 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.
  • Yakovlev VA. 2015. Role of nitric oxide in the radiation-induced bystander effect. Redox Biol. 6:396–400.
  • Yan W, Khan MK, Wu X, Simone CB, Fan J, Gressen E, Zhang X, Limoli CL, Bahig H, Tubin S, et al. 2020. Spatially fractionated radiation therapy: history, present and the future. Clin Transl Radiat Oncol. 20:30–38.
  • Yang H, Anzenberg V, Held KD. 2007. The time dependence of bystander responses induced by iron-ion radiation in normal human skin fibroblasts. Radiat Res. 168(3):292–298.
  • Yang H, Asaad N, Held KD. 2005. Medium-mediated intercellular communication is involved in bystander responses of X-ray-irradiated normal human fibroblasts. Oncogene. 24(12):2096–2103.
  • Yang X, Ma L, Ye Z, Shi W, Zhang L, Wang J, Yang H. 2021. Radiation-induced bystander effects may contribute to radiation-induced cognitive impairment. Int J Radiat Biol. 97(3):329–340.
  • Yang X, Xu S, Su Y, Chen B, Yuan H, Xu A, Wu L. 2018. Autophagy-Src regulates Connexin43-mediated gap junction intercellular communication in irradiated HepG2 cells. Radiat Res. 190(5):494–503.
  • Yokota Y, Funayama T, Mutou-Yoshihara Y, Ikeda H, Kobayashi Y. 2015. The bystander cell-killing effect mediated by nitric oxide in normal human fibroblasts varies with irradiation dose but not with radiation quality. Int J Radiat Biol. 91(5):383–388.
  • Yu KN. 2019. Radiation-induced rescue effect. J Radiat Res. 60(2):163–170.
  • Zhang Q, Matzke M, Schepmoes AA, Moore RJ, Webb-Robertson BJ, Hu Z, Monroe ME, Qian WJ, Smith RD, Morgan WF. 2014. High and low doses of ionizing radiation induce different secretome profiles in a human skin model. PLOS One. 9(3):e92332.
  • Zhao Y, de Toledo SM, Hu G, Hei TK, Azzam EI. 2014. Connexins and cyclooxygenase-2 crosstalk in the expression of radiation-induced bystander effects. Br J Cancer. 111(1):125–131.
  • Zhou H, Ivanov VN, Gillespie J, Geard CR, Amundson SA, Brenner DJ, Yu Z, Lieberman HB, Hei TK. 2005. Mechanism of radiation-induced bystander effect: role of the cyclooxygenase-2 signaling pathway. Proc Natl Acad Sci USA. 102(41):14641–14646.
  • Zhou H, Ivanov VN, Lien YC, Davidson M, Hei TK. 2008. Mitochondrial function and nuclear factor-kappaB-mediated signaling in radiation-induced bystander effects. Cancer Res. 68(7):2233–2240.
  • Zhou H, Randers-Pehrson G, Waldren CA, Vannais D, Hall EJ, Hei TK. 2000. Induction of a bystander mutagenic effect of alpha particles in mammalian cells. Proc Natl Acad Sci USA. 97(5):2099–2104.
  • Zhou H, Suzuki M, Randers-Pehrson G, Vannais D, Chen G, Trosko JE, Waldren CA, Hei TK. 2001. Radiation risk to low fluences of alpha particles may be greater than we thought. Proc Natl Acad Sci USA. 98(25):14410–14415.
  • Zhu A, Zhou H, Leloup C, Marino SA, Geard CR, Hei TK, Lieberman HB. 2005. Differential impact of mouse Rad9 deletion on ionizing radiation-induced bystander effects. Radiat Res. 164(5):655–661.
  • Zhu L, Hu S, Chen Q, Zhang H, Fu J, Zhou Y, Bai Y, Pan Y, Shao C. 2021. Macrophage contributes to radiation-induced anti-tumor abscopal effect on transplanted breast cancer by HMGB1/TNF-α signaling factors. Int J Biol Sci. 17(4):926–941.
  • Zirkle RE, Bloom W. 1953. Irradiation of parts of individual cells. Science. 117(3045):487–493.
  • Zirkle RE, Tobias CA. 1953. Effects of ploidy and linear energy transfer on radiobiological survival curves. Arch Biochem Biophys. 47(2):282–306.
  • Zong L, Zhu Y, Liang R, Zhao HB. 2016. Gap junction mediated miRNA intercellular transfer and gene regulation: a novel mechanism for intercellular genetic communication. Sci Rep. 6:19884.

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