bystander effect


Summary: The result of a positive or negative response (to drugs, for example) in one cell being passed onto other cells via the GAP JUNCTIONS or the intracellular milieu.

Top Publications

  1. Harada K, Nonaka T, Hamada N, Sakurai H, Hasegawa M, Funayama T, et al. Heavy-ion-induced bystander killing of human lung cancer cells: role of gap junctional intercellular communication. Cancer Sci. 2009;100:684-8 pubmed
    ..present study was to clarify the mechanisms of cell death induced by heavy-ion irradiation focusing on the bystander effect in human lung cancer A549 cells...
  2. Ebert M, Suchowerska N, Jackson M, McKenzie D. A mathematical framework for separating the direct and bystander components of cellular radiation response. Acta Oncol. 2010;49:1334-43 pubmed publisher
    ..A mathematical model for fractional tumor cell survival was developed incorporating components of cell killing due to direct radiation interactions and bystander signals resulting from non-local dose deposition...
  3. Choi V, Yum E, Konishi T, Oikawa M, Cheng S, Yu K. Triphasic low-dose response in zebrafish embryos irradiated by microbeam protons. J Radiat Res. 2012;53:475-81 pubmed
    ..At the same time, the experimental data were in line with induction of radiation-induced bystander effect as well as rescue effect in the zebrafish embryos, particular in those embryos with unirradiated cells.
  4. Mutou Yoshihara Y, Funayama T, Yokota Y, Kobayashi Y. Involvement of bystander effect in suppression of the cytokine production induced by heavy-ion broad beams. Int J Radiat Biol. 2012;88:258-66 pubmed publisher
    ..The suppression of cytokine production arose after irradiation with heavy-ions, and may also be induced in the surrounding non-irradiated cells via the bystander effect.
  5. Belloni P, Latini P, Palitti F. Radiation-induced bystander effect in healthy G(o) human lymphocytes: biological and clinical significance. Mutat Res. 2011;713:32-8 pubmed publisher
    ..However, when lymphocytes were irradiated with 0.1 Gy, no bystander effect with regard to viability, apoptosis, telomere length, and micronuclei was observed, although a high ..
  6. Garcia Rodríguez L, Pérez Torras S, Carrio M, Cascante A, Garcia Ribas I, Mazo A, et al. Connexin-26 is a key factor mediating gemcitabine bystander effect. Mol Cancer Ther. 2011;10:505-17 pubmed publisher
    ..killing whereas overexpression of Cx26 triggered increased GJIC and enhanced the gemcitabine cytotoxic bystander effect. Gemcitabine treatment of mice bearing tumors, with a high GJIC capacity, resulted in a significant delay in ..
  7. Hei T, Zhou H, Chai Y, Ponnaiya B, Ivanov V. Radiation induced non-targeted response: mechanism and potential clinical implications. Curr Mol Pharmacol. 2011;4:96-105 pubmed
    ..A better understanding of the mechanism of the non-targeted effects will be invaluable to assess its clinical relevance and ways in which the bystander phenomenon can be manipulated to increase therapeutic gain in radiotherapy. ..
  8. Gow M, Seymour C, Ryan L, Mothersill C. Induction of bystander response in human glioma cells using high-energy electrons: a role for TGF-beta1. Radiat Res. 2010;173:769-78 pubmed publisher
    ..These results indicate that bystander cell death can be induced in T98G glioma if a large enough radiation stress is applied and that TGF-beta1 plays a downstream role in this response. ..
  9. Boyman O. Bystander activation of CD4+ T cells. Eur J Immunol. 2010;40:936-9 pubmed publisher
    ..A study in this issue of the European Journal of Immunology sheds light on this aspect, suggesting that common gamma-chain cytokines including IL-2 might be involved in bystander activation of CD4(+) T cells. ..

More Information


  1. Cockburn I, Tse S, Zavala F. CD8+ T cells eliminate liver-stage Plasmodium berghei parasites without detectable bystander effect. Infect Immun. 2014;82:1460-4 pubmed publisher
    ..Rather, elimination of infected parasites is likely mediated by direct recognition of infected hepatocytes by antigen-specific CD8(+) T cells. ..
  2. Chai Y, Calaf G, Zhou H, Ghandhi S, Elliston C, Wen G, et al. Radiation induced COX-2 expression and mutagenesis at non-targeted lung tissues of gpt delta transgenic mice. Br J Cancer. 2013;108:91-8 pubmed publisher
    ..The PBIR induces DNA damage and mutagenesis in non-targeted lung tissues, especially in bronchial epithelial cells, and COX-2 has an essential role in bystander mutagenesis. ..
  3. Maeda M, Tomita M, Usami N, Kobayashi K. Bystander cell death is modified by sites of energy deposition within cells irradiated with a synchrotron X-ray microbeam. Radiat Res. 2010;174:37-45 pubmed publisher
    ..Our findings demonstrate that the induction of bystander cell death depends on the sites of energy deposition in irradiated cells. ..
  4. Ghandhi S, Ming L, Ivanov V, Hei T, Amundson S. Regulation of early signaling and gene expression in the alpha-particle and bystander response of IMR-90 human fibroblasts. BMC Med Genomics. 2010;3:31 pubmed publisher
    The existence of a radiation bystander effect, in which non-irradiated cells respond to signals from irradiated cells, is well established...
  5. Pozner R, Ure A, Jaquenod de Giusti C, D Atri L, Italiano J, Torres O, et al. Junín virus infection of human hematopoietic progenitors impairs in vitro proplatelet formation and platelet release via a bystander effect involving type I IFN signaling. PLoS Pathog. 2010;6:e1000847 pubmed publisher decreasing in vitro proplatelet formation, platelet release, and P-selectin externalization via a bystander effect. The decrease in platelet release was also TfR1-dependent, mimicked by poly(I:C), and type I interferon (IFN ..
  6. Tomita M, Maeda M, Maezawa H, Usami N, Kobayashi K. Bystander cell killing in normal human fibroblasts is induced by synchrotron X-ray microbeams. Radiat Res. 2010;173:380-5 pubmed publisher
    ..These results suggest that NO is the chief initiator/mediator of bystander cell killing induced by X-ray microbeams. ..
  7. Kobayashi Y, Funayama T, Hamada N, Sakashita T, Konishi T, Imaseki H, et al. Microbeam irradiation facilities for radiobiology in Japan and China. J Radiat Res. 2009;50 Suppl A:A29-47 pubmed
  8. Trepel M, Stoneham C, Eleftherohorinou H, Mazarakis N, Pasqualini R, Arap W, et al. A heterotypic bystander effect for tumor cell killing after adeno-associated virus/phage-mediated, vascular-targeted suicide gene transfer. Mol Cancer Ther. 2009;8:2383-91 pubmed publisher
    ..Finally, this heterotypic bystander effect is accompanied by a suppression of tumor growth in vivo that is independent of primary gene transfer into ..
  9. Ermakov A, Konkova M, Kostyuk S, Egolina N, Efremova L, Veiko N. Oxidative stress as a significant factor for development of an adaptive response in irradiated and nonirradiated human lymphocytes after inducing the bystander effect by low-dose X-radiation. Mutat Res. 2009;669:155-61 pubmed publisher
    ..effects are transmitted by means of extracellular DNA (ecDNA) fragments to nonirradiated cells (the so-called bystander effect, BE)...
  10. Facoetti A, Mariotti L, Ballarini F, Bertolotti A, Nano R, Pasi F, et al. Experimental and theoretical analysis of cytokine release for the study of radiation-induced bystander effect. Int J Radiat Biol. 2009;85:690-9 pubmed publisher
  11. Garcia Rodriguez L, Abate Daga D, Rojas A, Gonzalez J, Fillat C. E-cadherin contributes to the bystander effect of TK/GCV suicide therapy and enhances its antitumoral activity in pancreatic cancer models. Gene Ther. 2011;18:73-81 pubmed publisher
    ..A bystander effect, mediated by gap junctions, accounts for the transfer of toxic metabolites from TK-expressing cells to ..
  12. Rzeszowska Wolny J, Przybyszewski W, Widel M. Ionizing radiation-induced bystander effects, potential targets for modulation of radiotherapy. Eur J Pharmacol. 2009;625:156-64 pubmed publisher
  13. Mothersill C, Saroya R, Smith R, Singh H, Seymour C. Serum serotonin levels determine the magnitude and type of bystander effects in medium transfer experiments. Radiat Res. 2010;174:119-23 pubmed publisher
    ..variation in the ability to produce bystander effects and further suggest that serum batches should be protected from light and prescreened for their ability to produce a bystander effect using a positive control cell line.
  14. Määttä A, Samaranayake H, Pikkarainen J, Wirth T, Yla Herttuala S. Adenovirus mediated herpes simplex virus-thymidine kinase/ganciclovir gene therapy for resectable malignant glioma. Curr Gene Ther. 2009;9:356-67 pubmed
    ..Thus, the adenoviral mediated HSV-tk gene therapy is a promising new adjuvant treatment for patients with operable high-grade glioma. ..
  15. Ito S, Natsume A, Shimato S, Ohno M, Kato T, Chansakul P, et al. Human neural stem cells transduced with IFN-beta and cytosine deaminase genes intensify bystander effect in experimental glioma. Cancer Gene Ther. 2010;17:299-306 pubmed publisher
    ..In vitro studies showed that CD/IFN-beta-expressing NSCs exerted a remarkable bystander effect on human glioma cells after the application of 5-FC, as compared with parental NSCs and CD-expressing NSCs...
  16. Smith R, Wang J, Schultke E, Seymour C, Bräuer Krisch E, Laissue J, et al. Proteomic changes in the rat brain induced by homogenous irradiation and by the bystander effect resulting from high energy synchrotron X-ray microbeams. Int J Radiat Biol. 2013;89:118-27 pubmed publisher
    ..MBI) as a potential means of non-invasive brain tumor treatment by investigating the induction of a bystander effect in non-irradiated tissue...
  17. Chen S, Zhao Y, Zhao G, Han W, Bao L, Yu K, et al. Up-regulation of ROS by mitochondria-dependent bystander signaling contributes to genotoxicity of bystander effects. Mutat Res. 2009;666:68-73 pubmed publisher
    ..rho(0)) human-hamster hybrid cells to investigate mitochondrial effects on the genotoxicity in bystander effect through medium transfer experiments...
  18. Nelson G, Wordsworth J, Wang C, Jurk D, Lawless C, Martin Ruiz C, et al. A senescent cell bystander effect: senescence-induced senescence. Aging Cell. 2012;11:345-9 pubmed publisher
    ..Hepatocytes bearing senescence markers clustered together in mice livers. Thus, senescent cells can induce a bystander effect, spreading senescence towards their neighbours in vitro and, possibly, in vivo.
  19. Chakraborty A, Held K, Prise K, Liber H, Redmond R. Bystander effects induced by diffusing mediators after photodynamic stress. Radiat Res. 2009;172:74-81 pubmed publisher
    The bystander effect, whereby cells that are not traversed by ionizing radiation exhibit various responses when in proximity to irradiated cells, is well documented in the field of radiation biology, Here we demonstrate that considerable ..
  20. McMahon S, Butterworth K, McGarry C, Trainor C, O Sullivan J, Hounsell A, et al. A computational model of cellular response to modulated radiation fields. Int J Radiat Oncol Biol Phys. 2012;84:250-6 pubmed publisher
    ..The model predicts that the bystander effect makes a significant contribution to cell killing even in uniformly irradiated cells...
  21. Amano S, Gu C, Koizumi S, Tokuyama T, Namba H. Tumoricidal bystander effect in the suicide gene therapy using mesenchymal stem cells does not injure normal brain tissues. Cancer Lett. 2011;306:99-105 pubmed publisher
    ..In the present study, effect of the "bystander effect" associated with the MSCtk/GCV strategy on the background normal brain tissues was examined in both in ..
  22. Mancuso M, Pasquali E, Leonardi S, Rebessi S, Tanori M, Giardullo P, et al. Role of connexin43 and ATP in long-range bystander radiation damage and oncogenesis in vivo. Oncogene. 2011;30:4601-8 pubmed publisher
    ..Our data provide a novel hypothesis for transduction of distant bystander effects and suggest that the highly branched nervous system, similar to the vascular network, has an important role. ..
  23. Butterworth K, McGarry C, Trainor C, O Sullivan J, Hounsell A, Prise K. Out-of-field cell survival following exposure to intensity-modulated radiation fields. Int J Radiat Oncol Biol Phys. 2011;79:1516-22 pubmed publisher
    ..Validation of these observations in additional cell models may facilitate the refinement of existing radiobiological models and the observations considered important determinants of cell survival. ..
  24. Han W, Wu L, Chen S, Yu K. Exogenous carbon monoxide protects the bystander Chinese hamster ovary cells in mixed coculture system after alpha-particle irradiation. Carcinogenesis. 2010;31:275-80 pubmed publisher
    ..II) dimer [CO-releasing molecule (CORM-2)], on the toxicity of radiation-induced bystander effect (RIBE) after alpha-particle irradiation was studied in a mixed coculture system...
  25. Prise K, O Sullivan J. Radiation-induced bystander signalling in cancer therapy. Nat Rev Cancer. 2009;9:351-60 pubmed publisher
    ..has become clear is that, as well as responses to direct DNA damage, cell-cell signalling -- known as the bystander effect -- mediated through gap junctions and inflammatory responses may have an important role in the response of ..
  26. Ermakov A, Konkova M, Kostyuk S, Smirnova T, Malinovskaya E, Efremova L, et al. An extracellular DNA mediated bystander effect produced from low dose irradiated endothelial cells. Mutat Res. 2011;712:1-10 pubmed publisher
    ..cells was then supplemented with ecDNA(R), followed by analysing the cells along the series of parameters (bystander effect)...
  27. Kadhim M, Lee R, Moore S, Macdonald D, Chapman K, Patel G, et al. Genomic instability after targeted irradiation of human lymphocytes: evidence for inter-individual differences under bystander conditions. Mutat Res. 2010;688:91-4 pubmed publisher
    ..The findings may also be regarded as a radiation-induced genotype-dependent bystander effect triggering an instability phenotype.
  28. Yang G, Wu L, Chen S, Zhu L, Huang P, Tong L, et al. Mitochondrial dysfunction resulting from loss of cytochrome c impairs radiation-induced bystander effect. Br J Cancer. 2009;100:1912-6 pubmed publisher
    ..c, we showed here that cytochrome c-deficient cells had attenuated reactive oxygen species/nitric oxide and micronuclei induction to radiation-induced bystander signals, indicating cytochrome c is essential for the bystander effect.
  29. Lee F, Halliley J, Walsh E, Moscatiello A, Kmush B, Falsey A, et al. Circulating human antibody-secreting cells during vaccinations and respiratory viral infections are characterized by high specificity and lack of bystander effect. J Immunol. 2011;186:5514-21 pubmed publisher
    ..Additionally, high specificity of circulating ASCs after antigenic challenge highlights the diagnostic value of interrogating ASCs as an ideal single-time-point diagnostic immune surrogate for serology during acute infection. ..
  30. Trainor C, Butterworth K, McGarry C, McMahon S, O Sullivan J, Hounsell A, et al. DNA damage responses following exposure to modulated radiation fields. PLoS ONE. 2012;7:e43326 pubmed publisher
  31. Blyth B, Sykes P. Radiation-induced bystander effects: what are they, and how relevant are they to human radiation exposures?. Radiat Res. 2011;176:139-57 pubmed
    The term radiation-induced bystander effect is used to describe radiation-induced biological changes that manifest in unirradiated cells remaining within an irradiated cell population...
  32. Mothersill C, Smith R, Fazzari J, McNeill F, Prestwich W, Seymour C. Evidence for a physical component to the radiation-induced bystander effect?. Int J Radiat Biol. 2012;88:583-91 pubmed publisher
    ..We conclude that there must be a physical component in the mechanism such as a weak acoustic or electromagnetic signal. ..
  33. Li S, Gao Y, Pu K, Ma L, Song X, Liu Y. All-trans retinoic acid enhances bystander effect of suicide-gene therapy against medulloblastomas. Neurosci Lett. 2011;503:115-9 pubmed publisher
    ..2. However, our findings indicated that the bystander effect between C17.2tk and Daoy MB cells was weak compared to the bystander effect between NSCtk and C6 glioma cells...
  34. Fournier C, Barberet P, Pouthier T, Ritter S, Fischer B, Voss K, et al. No evidence for DNA and early cytogenetic damage in bystander cells after heavy-ion microirradiation at two facilities. Radiat Res. 2009;171:530-40 pubmed publisher
  35. Ivanov V, Zhou H, Ghandhi S, Karasic T, Yaghoubian B, Amundson S, et al. Radiation-induced bystander signaling pathways in human fibroblasts: a role for interleukin-33 in the signal transmission. Cell Signal. 2010;22:1076-87 pubmed publisher
  36. Sowa M, Goetz W, Baulch J, Pyles D, Dziegielewski J, Yovino S, et al. Lack of evidence for low-LET radiation induced bystander response in normal human fibroblasts and colon carcinoma cells. Int J Radiat Biol. 2010;86:102-13 pubmed publisher
    ..Nor did we see evidence of a high-LET, Fe ion radiation (1 GeV/n) induced bystander effect. However, direct comparison for 3...
  37. Hanot M, Hoarau J, Carriere M, Angulo J, Khodja H. Membrane-dependent bystander effect contributes to amplification of the response to alpha-particle irradiation in targeted and nontargeted cells. Int J Radiat Oncol Biol Phys. 2009;75:1247-53 pubmed publisher
    ..This study investigated their origin as well as their temporal and spatial impacts in the bystander effect. We employed a precise alpha-particle microbeam to target a small fraction of subconfluent osteoblastic cells ..
  38. Gerardi S. Ionizing radiation microbeam facilities for radiobiological studies in Europe. J Radiat Res. 2009;50 Suppl A:A13-20 pubmed
    ..An overview of the European microbeam facilities for radiobiological studies is presented and discussed in this paper. ..
  39. Rastogi S, Coates P, Lorimore S, Wright E. Bystander-type effects mediated by long-lived inflammatory signaling in irradiated bone marrow. Radiat Res. 2012;177:244-50 pubmed
    ..The findings also demonstrate the importance of studying tissue responses when considering the mechanisms underlying the consequences of radiation exposures. ..
  40. Shen H, Yu H, Liang P, Cheng H, XuFeng R, Yuan Y, et al. An acute negative bystander effect of ?-irradiated recipients on transplanted hematopoietic stem cells. Blood. 2012;119:3629-37 pubmed publisher
    ..However, whether irradiated recipients pose a proliferation-independent bystander effect on transplanted HSCs is unclear...
  41. Matsumoto H, Tomita M, Otsuka K, Hatashita M. A new paradigm in radioadaptive response developing from microbeam research. J Radiat Res. 2009;50 Suppl A:A67-79 pubmed
    ..The present review focuses on these two phenomena, and summarizes observations supporting their existence, and discusses the linkage between them in light of recent results obtained from experiments utilizing microbeams. ..
  42. Matuskova M, Hlubinova K, Pastorakova A, Hunakova L, Altanerova V, Altaner C, et al. HSV-tk expressing mesenchymal stem cells exert bystander effect on human glioblastoma cells. Cancer Lett. 2010;290:58-67 pubmed publisher
    ..GJIC) capability of AT-MSC with tumor cells further supports the exploitation of mesenchymal stem cells for approaches relying on the bystander effect. Biological consequences of these capabilities remain to be further explored.
  43. Xing L, Sun X, Deng X, Kotedia K, Urano M, Koutcher J, et al. Expression of the bifunctional suicide gene CDUPRT increases radiosensitization and bystander effect of 5-FC in prostate cancer cells. Radiother Oncol. 2009;92:345-52 pubmed publisher
    ..deaminase (CD) and uracil phosphoribosyltransferase (UPRT) can lead to greater radiosensitization and bystander effect than CD-expression alone. R3327-AT cell lines stably expressing CD or CDUPRT were generated...
  44. Han W, Yu K, Wu L, Wu Y, Wang H. Mechanism of protection of bystander cells by exogenous carbon monoxide: impaired response to damage signal of radiation-induced bystander effect. Mutat Res. 2011;709-710:1-6 pubmed publisher
    ..II) dimer (CORM-2), on the bystander cells from the toxicity of radiation-induced bystander effect (RIBE) was revealed in our previous study...
  45. Rajendran S, Harrison S, Thomas R, Tucker J. The role of mitochondria in the radiation-induced bystander effect in human lymphoblastoid cells. Radiat Res. 2011;175:159-71 pubmed
    Cells without intact mitochondrial DNA have been shown to lack the bystander effect, which is an energy-dependent process...
  46. Asur R, Thomas R, Tucker J. Chemical induction of the bystander effect in normal human lymphoblastoid cells. Mutat Res. 2009;676:11-6 pubmed publisher
    Many studies investigating the bystander effect have used ionizing radiation to evaluate this phenomenon, whereas very few have determined whether genotoxic chemicals are also capable of inducing this effect...
  47. Wang C, Smith R, Duhig J, Prestwich W, Byun S, McNeill F, et al. Neutrons do not produce a bystander effect in zebrafish irradiated in vivo. Int J Radiat Biol. 2011;87:964-73 pubmed publisher
    ..It was further found that neutrons did not induce a bystander effect in fish receiving signals from irradiated fish...
  48. Hamada N, Maeda M, Otsuka K, Tomita M. Signaling pathways underpinning the manifestations of ionizing radiation-induced bystander effects. Curr Mol Pharmacol. 2011;4:79-95 pubmed
    ..Such non-targeted responses are interrelated, and the bystander effect is further related with an adaptive response that manifests itself as the attenuated stressful biological ..
  49. Thomas Schoemann A, Lemare F, Mongaret C, Bermudez E, Chereau C, Nicco C, et al. Bystander effect of vinorelbine alters antitumor immune response. Int J Cancer. 2011;129:1511-8 pubmed publisher
    The bystander effect (BE) is the ability of malignant cells affected by an anticancer agent to induce damage in neighboring cancer cells...
  50. Cunha A, Oliveira R, Júnior A, Vaz N, Carvalho C. Different requirements for the adoptive transfer of oral tolerance and its indirect effects assessed by DTH and antibody responses in mice. Cell Immunol. 2009;258:152-60 pubmed publisher
    ..Interactions between cells and serum components may be necessary to bypass this barrier. ..
  51. Wright E. Manifestations and mechanisms of non-targeted effects of ionizing radiation. Mutat Res. 2010;687:28-33 pubmed publisher
  52. Cogan N, Baird D, Phillips R, Crompton L, Caldwell M, Rubio M, et al. DNA damaging bystander signalling from stem cells, cancer cells and fibroblasts after Cr(VI) exposure and its dependence on telomerase. Mutat Res. 2010;683:1-8 pubmed publisher
    The bystander effect is a feature of low dose radiation exposure and is characterized by a signaling process from irradiated cells to non irradiated cells, which causes DNA and chromosome damage in these 'nearest neighbour' cells...
  53. Zhang Y, Zhou J, Baldwin J, Held K, Prise K, Redmond R, et al. Ionizing radiation-induced bystander mutagenesis and adaptation: quantitative and temporal aspects. Mutat Res. 2009;671:20-5 pubmed publisher