Radiation-induced bystander effects: What are they, and how relevant are they to human radiation exposures?

Radiation Research

Volumn 176, Issue 2, 2011, Pages 139-157

  Blyth, Benjamin J ^a   Sykes, Pamela J ^a,b  

^a FLINDERS UNIVERSITY   (Australia)

^b FLINDERS MEDICAL CENTRE   (Australia)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOOXYGENASE 2; DNA FRAGMENT; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 8; NITRIC OXIDE; REACTIVE OXYGEN METABOLITE; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR ALPHA;

ABSCOPAL EFFECT; ASTROCYTE; BLADDER EPITHELIUM; BONE MARROW CELL; BYSTANDER EFFECT; CALCIUM TRANSPORT; CANCER RISK; CARCINOGENESIS; CARCINOMA CELL; CELL COMMUNICATION AND CELL CONTACT; CELL DAMAGE; CELL TYPE; DOSE RESPONSE; ENDOTHELIUM CELL; FIBROBLAST; GLIOMA CELL; HUMAN; INTESTINE EPITHELIUM CELL; KERATINOCYTE; LIVER CELL; LIVER CELL CARCINOMA; LUNG FIBROBLAST; LYMPHOMA CELL; NONHUMAN; PERIPHERAL LYMPHOCYTE; PRIORITY JOURNAL; RADIATION DOSE; RADIATION EXPOSURE; RADIATION RESPONSE; REVIEW; SIGNAL TRANSDUCTION; SKIN FIBROBLAST; SPLEEN LYMPHOCYTE; TUMOR CELL;

ANIMALS; BYSTANDER EFFECT; DOSE-RESPONSE RELATIONSHIP, RADIATION; ENVIRONMENTAL EXPOSURE; HUMANS; SIGNAL TRANSDUCTION; TIME FACTORS;

EID: 79961098043     PISSN: 00337587     EISSN: 19385404     Source Type: Journal    
DOI: 10.1667/RR2548.1     Document Type: Review

References (167)

1. H. Nagasawa and J. B. Little, Induction of sister chromatid exchanges by extremely low doses of alpha-particles. Cancer Res. 52, 6394-6396 (1992).
2. C. Mothersill and C. Seymour, Medium from irradiated human epithelial cells but not human fibroblasts reduces the clonogenic survival of unirradiated cells. Int. J. Radiat. Biol. 71, 421-427 (1997). (Pubitemid 27187398)
3. E. I. Azzam, S. M. de Toledo, T. Gooding and J. B. Little, 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, 497-504 (1998). (Pubitemid 28499048)
4. C. Mothersill and C. B. Seymour, 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, 256-262 (1998). (Pubitemid 28104286)
5. K. M. Prise, O. Belyakov, M. Folkard and B. D. Michael, Studies of bystander effects in human fibroblasts using a charged particle microbeam. Int. J. Radiat. Biol. 74, 793-798 (1998). (Pubitemid 28566248)
6. D. J. Brenner, J. B. Little and R. K. Sachs, The bystander effect in radiation oncogenesis: II. A quantitative model. Radiat. Res. 155, 402-408 (2001). (Pubitemid 32204256)
7. W. F. Morgan, Non-targeted and delayed effects of exposure to ionizing radiation: I. Radiation-induced genomic instability and bystander effects in vitro. Radiat. Res. 159, 567-580 (2003). (Pubitemid 36539236)
8. N. Hamada, H. Matsumoto, T. Hara and Y. Kobayashi, Intercellular and intracellular signaling pathways mediating ionizing radiation-induced bystander effects. J. Radiat. Res. (Tokyo) 48, 87-95 (2007). (Pubitemid 46535892)
9. C. A. Waldren, Classical radiation biology dogma, bystander effects and paradigm shifts. Hum. Exp. Toxicol. 23, 95 (2004).
10. R. Iyer and B. E. Lehnert, Alpha-particle-induced increases in the radioresistance of normal human bystander cells. Radiat. Res. 157, 3-7 (2002). (Pubitemid 34073381)
11. R. Iyer, B. E. Lehnert and R. Svensson, Factors underlying the cell growth-related bystander responses to α particles. Cancer Res. 60, 1290-1298 (2000). (Pubitemid 30151997)
12. Y. Ilnytskyy, I. Koturbash and O. Kovalchuk, Radiationinduced bystander effects in vivo are epigenetically regulated in a tissue-specific manner. Environ. Mol. Mutagen. 50, 105-113 (2009).
13. D. J. Newman, A natural products chemist looks at the bystander effect! Mutat. Res. 597, 39-42 (2006).
14. W. F. Morgan and M. B. Sowa, Non-targeted effects of ionizing radiation: implications for risk assessment and the radiation dose response profile. Health Phys. 97, 426-432 (2009).
15. S. R. Moore, S. Marsden, D. Macdonald, S. Mitchell, M. Folkard, B. Michael, D. T. Goodhead, K. M. Prise and M. A. Kadhim, Genomic instability in human lymphocytes irradiated with individual charged particles: involvement of tumor necrosis factor a in irradiated cells but not bystander cells. Radiat. Res. 163, 183-190 (2005). (Pubitemid 40170768)
16. G. Kashino, T. Kondoh, N. Nariyama, K. Umetani, T. Ohigashi, K. Shinohara, A. Kurihara, M. Fukumoto, H. Tanaka and K. Ono, Induction of DNA double-strand breaks and cellular migration through bystander effects in cells irradiated with the slit-type microplanar beam of the Spring-8 Synchrotron. Int. J. Radiat. Oncol. Biol. Phys. 74, 229-236 (2009).
17. B. I. Gerashchenko and R. W. Howell, Bystander cell proliferation is modulated by the number of adjacent cells that were exposed to ionizing radiation. Cytometry A 66, 62-70 (2005). (Pubitemid 40868920)
18. S. Gaillard, D. Pusset, S. M. de Toledo, M. Fromm and E. I. Azzam, Propagation distance of the alpha-particle-induced bystander effect: the role of nuclear traversal and gap junction communication. Radiat. Res. 171, 513-520 (2009).
19. I. Koturbash, A. Boyko, R. Rodriguez-Juarez, R. J. McDonald, V. P. Tryndyak, I. Kovalchuk, I. P. Pogribny and O. Kovalchuk, Role of epigenetic effectors in maintenance of the long-term persistent bystander effect in spleen in vivo. Carcinogenesis 28, 1831-1838 (2007). (Pubitemid 47289047)
20. C. Mothersill, C. Bucking, R. W. Smith, N. Agnihotri, A. O'Neill, M. Kilemade and C. B. Seymour, Communication of radiation-induced stress or bystander signals between fish in vivo. Environ. Sci. Technol. 40, 6859-6864 (2006). (Pubitemid 44721934)
21. M. Ojima, N. Ban and M. Kai, DNA double-strand breaks induced by very low X-ray doses are largely due to bystander effects. Radiat. Res. 170, 365-371 (2008).
22. C. Mothersill and C. Seymour, Radiation-induced bystander effects: past history and future directions. Radiat. Res. 155, 759-767 (2001). (Pubitemid 32494601)
23. A. Deshpande, E. H. Goodwin, S. M. Bailey, B. L. Marrone and B. E. Lehnert, Alpha-particle-induced sister chromatid exchange in normal human lung fibroblasts: evidence for an extranuclear target. Radiat. Res. 145, 260-267 (1996). (Pubitemid 26082619)
24. G. Schettino, M. Folkard, K. M. Prise, B. Vojnovic and B. D. Michael, Upgrading of the Gray Laboratory soft X ray microprobe with V79 survival measurements following irradiation of one or all cells with a Ck X ray beam of different size. Radiat. Prot. Dosimetry 99, 287-288 (2002).
25. T. K. Hei, H. Zhou, V. N. Ivanov, M. Hong, H. B. Lieberman, D. J. Brenner, S. A. Amundson and C. R. Geard, Mechanism of radiation-induced bystander effects: a unifying model. J. Pharm. Pharmacol. 60, 943-950 (2008).
26. G. Sgouros, S. J. Knox, M. C. Joiner, W. F. Morgan and A. I. Kassis, MIRD Continuing Education: Bystander and low doserate effects: Are these relevant to radionuclide therapy? J. Nucl. Med. 48, 1683-1691 (2007). (Pubitemid 47572716)
27. W. F. Morgan and M. B. Sowa, Non-targeted bystander effects induced by ionizing radiation. Mutat. Res. 616, 159-164 (2007). (Pubitemid 46206080)
28. K. Prise, M. Folkard and B. Michael, A review of the bystander effect and its implications for low-dose exposure. Radiat. Prot. Dosimetry 104, 347-355 (2003). (Pubitemid 37265729)
29. B. Djordjevic, Bystander effects: A concept in need of clarification. BioEssays 22, 286-290 (2000). (Pubitemid 30144421)
30. S. A. Lorimore and E. G. Wright, Radiation-induced genomic instability and bystander effects: related inflammatory-type responses to radiation-induced stress and injury? A review. Int. J. Radiat. Biol. 79, 15-25 (2003). (Pubitemid 36140233)
31. E. J. Hall, The bystander effect. Health Phys. 85, 31-35 (2003). (Pubitemid 36706037)
32. Z. Goldberg and B. E. Lehnert, Radiation-induced effects in unirradiated cells: a review and implications in cancer. Int. J. Oncol. 21, 337-349 (2002).
33. F. Ballarini, M. Biaggi, A. Ottolenghi and O. Sapora, Cellular communication and bystander effects: a critical review for modelling low-dose radiation action. Mutat. Res. 501, 1-12 (2002). (Pubitemid 34270645)
34. L. E. Feinendegen, Relative implications of protective responses versus damage induction at low dose and low-dose-rate exposures, using the microdose approach. Radiat. Prot. Dosimetry 104, 337-346 (2003). (Pubitemid 37265728)
35. NCRP, Evaluation of the Linear-Nonthreshold Dose-Response Model for Ionizing Radiation. Report No. 136, National Council on Radiation Protection and Measurements, Bethesda, MD, 2001.
36. J. B. Little, Cellular radiation effects and the bystander response. Mutat. Res. 597, 113-118 (2006).
37. NCRP, Screening of Humans for Security Purposes Using Ionizing Radiation Scanning Systems. Commentary No. 16, National Council on Radiation Protection and Measurements, Bethesda, MD, 2003.
38. United Nations Scientific Committee on the Effects of Atomic Radiation, Sources and Effects of Ionizing Radiation. UNSCEAR 2000 Report, Vol. I. United Nations, New York, 2000.
39. J. F. Bottollier-Depois, Q. Chau, P. Bouisset, G. Kerlau, L. Plawinski and L. Lebaron-Jacobs, Assessing exposure to cosmic radiation during long-haul flights. Radiat. Res. 153, 526-532 (2000). (Pubitemid 30252600)
40. R. H. Mole, Whole body irradiation: radiobiology or medicine? Br. J. Radiol. 26, 234-241 (1953).
41. S. J. Ko, X. Y. Liao, S. Molloi, E. Elmore and J. L. Redpath, Neoplastic transformation in vitro after exposure to low doses of mammographic-energy X rays: quantitative and mechanistic aspects. Radiat. Res. 162, 646-654 (2004). (Pubitemid 39552893)
42. C. Mothersill, R. W. Smith, N. Agnihotri and C. B. Seymour, Characterization of a radiation-induced stress response communicated in vivo between zebrafish. Environ. Sci. Technol. 41, 3382-3387 (2007). (Pubitemid 46713407)
43. K. Dowling, C. Seymour and C. Mothersill, Delayed cell death and bystander effects in the progeny of Chinook salmon embryo cells exposed to radiation and a range of aquatic pollutants. Int. J. Radiat. Biol. 81, 89-96 (2005). (Pubitemid 40674536)
44. L. C. DeVeaux, L. S. Durtschi, J. G. Case and D. P. Wells, Bystander effects in unicellular organisms. Mutat. Res. 597, 78-86 (2006).
45. P. K. McGregor, Ed., Animal Communication Networks. University Press, Cambridge, 2005.
46. P. Karlson and M. Lüscher, Pheromones: a new term for a class of biologically active substances. Nature 183, 55-56 (1959).
47. C. Fuqua, M. R. Parsek and E. P. Greenberg, Regulation of gene expression by cell-to-cell communication: Acylhomoserine lactone quorum sensing. Annu. Rev. Genet. 35, 439-468 (2001). (Pubitemid 34032983)
48. S. M. Freeman, C. N. Abboud, K. A. Whartenby, C. H. Packman, D. S. Koeplin, F. L. Moolten and G. N. Abraham, The "bystander effect": tumor regression when a fraction of the tumor mass is genetically modified. Cancer Res. 53, 5274-5283 (1993). (Pubitemid 23333399)
49. J. M. Kaminski, E. Shinohara, J. B. Summers, K. J. Niermann, A. Morimoto and J. Brousal, The controversial abscopal effect. Cancer Treat Rev. 31, 159-172 (2005). (Pubitemid 40790388)
50. K. Camphausen, M. A. Moses, C. Ménard, M. Sproull, W-D. Beecken, J. Folkman and M. S. O'Reilly, Radiation abscopal antitumor effect is mediated through p53. Cancer Res. 63, 1990-1993 (2003). (Pubitemid 36460868)
51. W. F. Morgan, 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, 581-596 (2003). (Pubitemid 36539237)
52. I. Koturbash, K. Kutanzi, K. Hendrickson, R. Rodriguez-Juarez, D. Kogosov and O. Kovalchuk, Radiation-induced bystander effects in vivo are sex specific. Mutat. Res. 642, 28-36 (2008).
53. C. Mothersill and C. B. Seymour, Bystander and delayed effects after fractionated radiation exposure. Radiat. Res. 158, 626-633 (2002). (Pubitemid 35266195)
54. C. Mothersill, R. J. Seymour and C. B. Seymour, Bystander effects in repair-deficient cell lines. Radiat. Res. 161, 256-263 (2004). (Pubitemid 40797067)
55. C. Mothersill, R. Saroya, R. W. Smith, H. Singh and C. B. Seymour, Serum serotonin levels determine the magnitude and type of bystander effects in medium transfer experiments. Radiat. Res. 174, 119-123 (2010).
56. ICRP, Low-Dose Extrapolation of Radiation Related Cancer Risk. Publication 99, Annals of the ICRP, Vol. 35, Elsevier, Amsterdam, 2006.
57. B. J. Blyth, E. I. Azzam, R. W. Howell, R. J. Ormsby, A. H. Staudacher and P. J. Sykes, An adoptive transfer method to detect low-dose radiation-induced bystander effects in vivo. Radiat. Res. 173, 125-137 (2010).
58. M. Mancuso, E. Pasquali, S. Leonardi, M. Tanori, S. Rebessi, V. Di Majo, S. Pazzaglia, M. P. Toni, M. Pimpinella and A. Saran, Oncogenic bystander radiation effects in Patched heterozygous mouse cerebellum. Proc. Natl. Acad. Sci. USA 105, 12445-12450 (2008).
59. H. Kishikawa, K. Wang, S. J. Adelstein and A. I. Kassis, Inhibitory and stimulatory bystander effects are differentially induced by iodine-125 and iodine-123. Radiat. Res. 165, 688-694 (2006). (Pubitemid 43831018)
60. G. E. Watson, S. A. Lorimore, D. A. Macdonald and E. G. Wright, chromosomal instability in unirradiated cells induced in vivo by a bystander effect of ionizing radiation. Cancer Res. 60, 5608-5611 (2000).
61. L. Y. Xue, N. J. Butler, G. M. Makrigiorgos, S. J. Adelstein and A. I. Kassis, Bystander effect produced by radiolabeled tumor cells in vivo. Proc. Natl. Acad. Sci. USA 99, 13765-13770 (2002). (Pubitemid 35215455)
62. I. K. Khvostunov and H. Nikjoo, Computer modelling of radiation-induced bystander effect. J. Radiol. Prot. 22, A33-37 (2002).
63. H. Nikjoo and I. K. Khvostunov, Biophysical model of the radiation-induced bystander effect. Int. J. Radiat. Biol. 79, 43-52 (2003). (Pubitemid 36140236)
64. M. P. Little, J. A. Filipe, K. M. Prise, M. Folkard and O. V. Belyakov, A model for radiation-induced bystander effects, with allowance for spatial position and the effects of cell turnover. J. Theor. Biol. 232, 329-338 (2005). (Pubitemid 39575105)
65. H. Schöllnberger, R. E. J. Mitchel, D. J. Crawford-Brown and W. Hofmann, A model for the induction of chromosome aberrations through direct and bystander mechanisms. Radiat. Prot. Dosimetry 122, 275-281 (2006). (Pubitemid 47090464)
66. I. Shuryak, R. K. Sachs and D. J. Brenner, Biophysical models of radiation bystander effects: 1. Spatial effects in three-dimensional tissues. Radiat. Res. 168, 741-749 (2007). (Pubitemid 351295111)
67. M. Richard, R. P. Webb, K. J. Kirkby and N. F. Kirkby, A computer model of the bystander effect: Effects of individual behaviours on the population response. Appl. Radiat. Isot. 67, 440-442 (2009).
68. H. Fakir, W. Hofmann, W. Y. Tan and R. K. Sachs, Triggering-response model for radiation-induced bystander effects. Radiat. Res. 171, 320-331 (2009).
69. M. P. Little, The bystander effect model of Brenner and Sachs fitted to lung cancer data in 11 cohorts of underground miners, and equivalence of fit of a linear relative risk model with adjustment for attained age and age at exposure. J. Radiol. Prot. 24, 243-255 (2004). (Pubitemid 39264305)
70. D. J. Brenner and R. K. Sachs, Do low dose-rate bystander effects influence domestic radon risks? Int. J. Radiat. Biol. 78, 593-604 (2002). (Pubitemid 34693919)
71. O. Belyakov, A. M. Malcolmson, M. Folkard, K. M. Prise and B. D. Michael, Direct evidence for a bystander effect of ionizing radiation in primary human fibroblasts. Br. J. Cancer 84, 674-679 (2001). (Pubitemid 32239002)
72. C. Shao, V. Stewart, M. Folkard, B. D. Michael and K. M. Prise, Nitric oxide-mediated signaling in the bystander response of individually targeted glioma cells. Cancer Res. 63, 8437-8442 (2003). (Pubitemid 37549500)
73. B. Ponnaiya, G. Jenkins-Baker, D. J. Brenner, E. J. Hall, G. Randers-Pehrson and C. R. Geard, Biological responses in known bystander cells relative to known microbeam-irradiated cells. Radiat. Res. 162, 426-432 (2004). (Pubitemid 39388164)
74. R. Wang and J. A. Coderre, A bystander effect in alpha-particle irradiations of human prostate tumor cells. Radiat. Res. 164, 711-722 (2005). (Pubitemid 41692718)
75. L. B. Smilenov, E. J. Hall, W. M. Bonner and O. A. Sedelnikova, A microbeam study of DNA double-strand breaks in bystander primary human fibroblasts. Radiat. Prot. Dosimetry 122, 256-259 (2006). (Pubitemid 47090460)
76. C. Shao, Y. Furusawa, Y. Kobayashi, T. Funayama and S. Wada, Bystander effect induced by counted high-LET particles in confluent human fibroblasts: a mechanistic study. FASEB J. 17, 1422-1427 (2003). (Pubitemid 36935656)
77. S. G. Sawant, G. Randers-Pehrson, C. R. Geard, D. J. Brenner and E. J. Hall, The bystander effect in radiation oncogenesis: I. Transformation in C3H 10T 1/2 cells in vitro can be initiated in the unirradiated neighbors of irradiated cells. Radiat. Res. 155, 397-401 (2001). (Pubitemid 32204255)
78. S. G. Sawant, W. Zheng, K. M. Hopkins, G. Randers-Pehrson, H. B. Lieberman and E. J. Hall, The radiation-induced bystander effect for clonogenic survival. Radiat. Res. 157, 361-364 (2002). (Pubitemid 34267247)
79. G. Schettino, M. Folkard, B. D. Michael and K. M. Prise, Lowdose binary behavior of bystander cell killing after microbeam irradiation of a single cell with focused C (k) X rays. Radiat. Res. 163, 332-336 (2005). (Pubitemid 40293542)
80. M. Tomita, M. Maeda, H. Maezawa, N. Usami and K. Kobayashi, Bystander cell killing in normal human fibroblasts is induced by synchrotron X-ray microbeams. Radiat. Res. 173, 380-385 (2010).
81. B. I. Gerashchenko and R. W. Howell, Cell proximity is a prerequisite for the proliferative response of bystander cells cocultured with cells irradiated with gamma-rays. Cytometry A 56, 71-80 (2003). (Pubitemid 38035918)
82. B. I. Gerashchenko and R. W. Howell, Flow cytometry as a strategy to study radiation-induced bystander effects in coculture systems. Cytometry A 54, 1-7 (2003). (Pubitemid 37521490)
83. A. Bishayee, H. Z. Hill, D. Stein, D. V. Rao and R. W. Howell, Free radical-initiated and gap junction-mediated bystander effect due to nonuniform distribution of incorporated radioactivity in a three-dimensional tissue culture model. Radiat. Res. 155, 335-344 (2001). (Pubitemid 32125985)
84. 125I. Micron 33, 127-132 (2002). (Pubitemid 32997012)
85. R. Persaud, H. Zhou, S. E. Baker, T. K. Hei and E. J. Hall, Assessment of low linear energy transfer radiation-induced bystander mutagenesis in a three-dimensional culture model. Cancer Res. 65, 9876-9882 (2005). (Pubitemid 41541467)
86. D. A. Lewis, B. M. Mayhugh, Y. Qin, K. Trott and M. S. Mendonca, Production of delayed death and neoplastic transformation in CGL1 cells by radiation-induced bystander effects. Radiat. Res. 156, 251-258 (2001). (Pubitemid 32801094)
87. O. Nuta and F. Darroudi, The impact of the bystander effect on the low-dose hypersensitivity phenomenon. Radiat. Environ. Biophys. 47, 265-274 (2008).
88. C. B. Seymour and C. Mothersill, Relative contribution of bystander and targeted cell killing to the low-dose region of the radiation dose-response curve. Radiat. Res. 153, 508-511 (2000). (Pubitemid 30252597)
89. Z. Liu, C. E. Mothersill, F. E. McNeill, F. M. Lyng, S. H. Byun, C. B. Seymour and W. V. Prestwich, A dose threshold for a medium transfer bystander effect for a human skin cell line. Radiat. Res. 166, 19-23 (2006). (Pubitemid 44051221)
90. O. Belyakov, S. A. Mitchell, D. Parikh, G. Randers-Pehrson, S. A. Marino, S. A. Amundson, C. R. Geard and D. J. Brenner, Biological effects in unirradiated human tissue induced by radiation damage up to 1 mm away. Proc. Natl. Acad. Sci. USA 102, 14203-14208 (2005). (Pubitemid 41429676)
91. D. Frankenberg, K. D. Greif and U. Giesen, 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, 59-67 (2006).
92. C. Shao, M. Aoki and Y. Furusawa, Medium-mediated bystander effects on HSG cells co-cultivated with cells irradiated by X-rays or a 290 MeV/u carbon beam. J. Radiat. Res. (Tokyo) 42, 305-316 (2001). (Pubitemid 33613208)
93. S. Z. Liu, S. Z. Jin and X. D. Liu, Radiation-induced bystander effect in immune response. Biomed. Environ. Sci. 17, 40-46 (2004).
94. H. Zhou, V. N. Ivanov, J. Gillespie, C. R. Geard, S. A. Amundson, D. J. Brenner, Z. Yu, H. B. Lieberman and T. K. Hei, Mechanism of radiation-induced bystander effect: Role of the cyclooxygenase-2 signaling pathway. Proc. Natl. Acad. Sci. USA 102, 14641-14646 (2005). (Pubitemid 41457109)
95. P. K. Narayanan, K. E. LaRue, E. H. Goodwin and B. E. Lehnert, Alpha particles induce the production of interleukin-8 by human cells. Radiat. Res. 152, 57-63 (1999). (Pubitemid 29296246)
96. H. Matsumoto, S. Hayashi, M. Hatashita, H. Shioura, T. Ohtsubo, R. Kitai, T. Ohnishi, O. Yukawa, Y. Furusawa and E. Kano, Induction of radioresistance to accelerated carbon-ion beams in recipient cells by nitric oxide excreted from irradiated donor cells of human glioblastoma. Int. J. Radiat. Biol. 76, 1649-1657 (2000).
97. E. I. Azzam, S. M. de Toledo and J. B. Little, Oxidative metabolism, gap junctions and the ionizing radiation-induced bystander effect. Oncogene 22, 7050-7057 (2003). (Pubitemid 37386674)
98. H. Nagasawa, A. Cremesti, R. Kolesnick, Z. Fuks and J. B. Little, Involvement of membrane signaling in the bystander effect in irradiated cells. Cancer Res. 62, 2531-2534 (2002). (Pubitemid 34462730)
99. A. V. Ermakov, S. V. Kostiuk, N. A. Egolina, E. M. Malinovskaia, N. N. Veiko and D. M. Spitkovskii, [The DNA fragments obtained from the culture media exposed to adaptive doses of the ionizing radiation as factors of stress signaling between lymphocytes and bystander cells]. Radiats. Biol. Radioecol. 47, 133-140 (2007).
100. F. M. Lyng, P. Maguire, B. McClean, C. Seymour and C. Mothersill, The involvement of calcium and MAP kinase signaling pathways in the production of radiation-induced bystander effects. Radiat. Res. 165, 400-409 (2006).
101. H. Zhou, V. N. Ivanov, Y-C. Lien, M. Davidson and T. K. Hei, Mitochondrial function and nuclear factor-κB-mediated signaling in radiation-induced bystander effects. Cancer Res. 68, 2233-2240 (2008). (Pubitemid 351521796)
102. B. Hu, W. Han, L. Wu, H. Feng, X. Liu, L. Zhang, A. Xu, T. K. Hei and Z. Yu, In situ visualization of DSBs to assess the extranuclear/extracellular effects induced by low-dose a-particle irradiation. Radiat. Res. 164, 286-291 (2005). (Pubitemid 41233782)
103. L. Huo, H. Nagasawa and J. B. Little, HPRT mutants induced in bystander cells by very low fluences of alpha particles result primarily from point mutations. Radiat. Res. 156, 521-525 (2001). (Pubitemid 33027521)
104. H. Zhou, G. Randers-Pehrson, M. Suzuki, C. A. Waldren and T. K. Hei, Genotoxic damage in non-irradiated cells: contribution from the bystander effect. Radiat. Prot. Dosimetry 99, 227-232 (2002).
105. J. B. Little, H. Nagasawa, G. C. Li and D. J. Chen, Involvement of the nonhomologous end joining DNA repair pathway in the bystander effect for chromosomal aberrations. Radiat. Res. 159, 262-267 (2003). (Pubitemid 36182405)
106. O. Belyakov, M. Folkard, C. Mothersill, K. M. Prise and B. D. Michael, A proliferation-dependent bystander effect in primary porcine and human urothelial explants in response to targeted irradiation. Br. J. Cancer 88, 767-774 (2003). (Pubitemid 36411458)
107. L. A. Ryan, R. W. Smith, C. B. Seymour and C. E. Mothersill, Dilution of irradiated cell conditioned medium and the bystander effect. Radiat. Res. 169, 188-196 (2008). (Pubitemid 351295076)
108. G. Kashino, K. M. Prise, G. Schettino, M. Folkard, B. Vojnovic, B. D. Michael, K. Suzuki, S. Kodama and M. Watanabe, Evidence for induction of DNA double strand breaks in the bystander response to targeted soft X-rays in CHO cells. Mutat. Res. 556, 209-215 (2004). (Pubitemid 39371194)
109. G. Schettino, M. Folkard, K. M. Prise, B. Vojnovic, K. D. Held and B. D. Michael, Low-dose studies of bystander cell killing with targeted soft X rays. Radiat. Res. 160, 505-511 (2003). (Pubitemid 38055197)
110. A. H. Staudacher, B. J. Blyth, M. D. Lawrence, R. J. Ormsby, E. Bezak and P. J. Sykes, If bystander effects for apoptosis occur in spleen after low-dose irradiation in vivo then the magnitude of the effect falls within the range of normal homeostatic apoptosis. Radiat. Res. 174, 727-731 (2010).
111. E. I. Azzam, S. M. de Toledo and J. B. Little, Stress signaling from irradiated to non-irradiated cells. Curr. Cancer Drug Targets 4, 53-64 (2004). (Pubitemid 38332564)
112. C. Fournier, D. Becker, M. Winter, P. Barberet, M. Heiss, B. Fischer, J. Topsch and G. Taucher-Scholz, Cell cycle-related bystander responses are not increased with LET after heavy-ion irradiation. Radiat. Res. 167, 194-206 (2007). (Pubitemid 46214667)
113. B. Hu, L. Wu, W. Han, L. Zhang, S. Chen, A. Xu, T. K. Hei and Z. Yu, The time and spatial effects of bystander response in mammalian cells induced by low dose radiation. Carcinogenesis 27, 245-251 (2006). (Pubitemid 43159876)
114. E. Blakely, A. Thompson, P. Chang, R. Schwarz, K. Bjornstad, C. Rosen, H. Holman, D. Holman and B. Parvin, Multicellular crosstalk in radiation damage. In Low Dose Radiation Research Program: Investigators' Workshop VIII, p. 21. Bethesda, MD, April 2009.
115. B. E. Leonard, The range of the bystander effect signal in three-dimensional tissue and estimation of the range in human lung tissue at low radon levels. Radiat. Res. 171, 374-378 (2009).
116. M. D. Gow, C. B. Seymour, L. A. Ryan and C. E. Mothersill, Induction of bystander response in human glioma cells using high-energy electrons: a role for TGF-β. Radiat. Res. 173, 769-778 (2010).
117. M. Boyd, S. C. Ross, J. Dorrens, N. E. Fullerton, K. W. Tan, M. R. Zalutsky and R. J. Mairs, Radiation-induced biologic bystander effect elicited in vitro by targeted radiopharmaceuticals labeled with α-, β-, and Auger electronemitting radionuclides. J. Nucl. Med. 47, 1007-1015 (2006). (Pubitemid 46939954)
118. C. Fournier, P. Barberet, T. Pouthier, S. Ritter, B. Fischer, K. O. Voss, T. Funayama, N. Hamada, Y. Kobayashi and G. Taucher-Scholz, No evidence for DNA and early cytogenetic damage in bystander cells after heavy-ion microirradiation at two facilities. Radiat. Res. 171, 530-540 (2009).
119. T. Groesser, B. Cooper and B. Rydberg, Lack of bystander effects from high-LET radiation for early cytogenetic end points. Radiat. Res. 170, 794-802 (2008).
120. Y. Kanasugi, N. Hamada, S. Wada, T. Funayama, T. Sakashita, T. Kakizaki, Y. Kobayashi and K. Takakura, Role of DNA-PKcs in the bystander effect after low-or high-LET irradiation. Int. J. Radiat. Biol. 83, 73-80 (2007).
121. H. Yang, V. Anzenberg and K. D. Held, The time dependence of bystander responses induced by iron-ion radiation in normal human skin fibroblasts. Radiat. Res. 168, 292-298 (2007). (Pubitemid 351295131)
122. C. Shao, M. Aoki and Y. Furusawa, Bystander effect on cell growth stimulation in neoplastic HSGc cells induced by heavyion irradiation. Radiat. Environ. Biophys. 42, 183-187 (2003). (Pubitemid 37518062)
123. C. Shao, Y. Furusawa, M. Aoki, H. Matsumoto and K. Ando, Nitric oxide-mediated bystander effect induced by heavy-ions in human salivary gland tumour cells. Int. J. Radiat. Biol. 78, 837-844 (2002).
124. C. Shao, M. Aoki and Y. Furusawa, Bystander effect in lymphoma cells vicinal to irradiated neoplastic epithelial cells: nitric oxide is involved. J. Radiat. Res. (Tokyo) 45, 97-103 (2004). (Pubitemid 38698655)
125. S. A. Mitchell, S. A. Marino, D. J. Brenner and E. J. Hall, Bystander effect and adaptive response in C3H 10T 1/2 cells. Int. J. Radiat. Biol. 80, 465-472 (2004). (Pubitemid 39037102)
126. V. Anzenberg, S. Chandiramani and J. A. Coderre, LET-dependent bystander effects caused by irradiation of human prostate carcinoma cells with X rays or alpha particles. Radiat. Res. 170, 467-476 (2008).
127. R. Baskar, A. S. Balajee and C. R. Geard, Effects of low and high LET radiations on bystander human lung fibroblast cell survival. Int. J. Radiat. Biol. 83, 551-559 (2007). (Pubitemid 47035913)
128. M. Boyd, A. Sorensen, A. G. McCluskey and R. J. Mairs, Radiation quality-dependent bystander effects elicited by targeted radionuclides. J. Pharm. Pharmacol. 60, 951-958 (2008).
129. W. Han, L. Wu, B. Hu, L. Zhang, S. Chen, L. Bao, Y. Zhao, A. Xu and Z. Yu, The early and initiation processes of radiationinduced bystander effects involved in the induction of DNA double strand breaks in non-irradiated cultures. Br. J. Radiol. 80, S7-12 (2007). (Pubitemid 47517794)
130. O. Belyakov, M. Folkard, C. Mothersill, K. M. Prise and B. D. Michael, Bystander-induced apoptosis and premature differentiation in primary urothelial explants after charged particle microbeam irradiation. Radiat. Prot. Dosimetry 99, 249-251 (2002).
131. O. A. Sedelnikova, A. Nakamura, O. Kovalchuk, I. Koturbash, S. A. Mitchell, S. A. Marino, D. J. Brenner and W. M. Bonner, DNA double-strand breaks form in bystander cells after microbeam irradiation of three-dimensional human tissue models. Cancer Res. 67, 4295-4302 (2007). (Pubitemid 46815077)
132. M. Suzuki, H. Zhou, C. R. Geard and T. K. Hei, Effect of medium on chromatin damage in bystander mammalian cells. Radiat. Res. 162, 264-269 (2004). (Pubitemid 39295427)
133. K. L. Burr, J. I. Robinson, S. Rastogi, M. T. Boylan, P. J. Coates, S. A. Lorimore and E. G. Wright, Radiation-induced delayed bystander-type effects mediated by hemopoietic Cells. Radiat. Res. 173, 760-768 (2010).
134. S. A. Mitchell, G. Randers-Pehrson, D. J. Brenner and E. J. Hall, The bystander response in C3H 10T 1/2 cells: The influence of cell-to-cell contact. Radiat. Res. 161, 397-401 (2004). (Pubitemid 40754236)
135. A. M. Vines, F. M. Lyng, B. McClean, C. Seymour and C. E. Mothersill, Bystander signal production and response are independent processes which are cell line dependent. Int. J. Radiat. Biol. 84, 83-90 (2008). (Pubitemid 351197934)
136. G. I. Terzoudi, C. Donta-Bakoyianni, G. Iliakis and G. E. Pantelias, Investigation of bystander effects in hybrid cells by means of cell fusion and premature chromosome condensation induction. Radiat. Res. 173, 789-801 (2010).
137. L. A. Ryan, C. B. Seymour, M. C. Joiner and C. E. Mothersill, Radiation-induced adaptive response is not seen in cell lines showing a bystander effect but is seen in lines showing HRS/IRR response. Int. J. Radiat. Biol. 85, 87-95 (2009).
138. M. H. Gaugler, M. Neunlist, S. Bonnaud, P. Aubert, M. Benderitter and F. Paris, Intestinal epithelial cell dysfunction is mediated by an endothelial-specific radiation-induced bystander effect. Radiat. Res. 167, 185-193 (2007). (Pubitemid 46214666)
139. C. Shao, M. Folkard, B. D. Michael and K. M. Prise, Bystander signaling between glioma cells and fibroblasts targeted with counted particles. Int. J. Cancer 116, 45-51 (2005). (Pubitemid 40827753)
140. S. Burdak-Rothkamm, S. C. Short, M. Folkard, K. Rothkamm and K. M. Prise, ATR-dependent radiation-induced gamma H2AX foci in bystander primary human astrocytes and glioma cells. Oncogene 26, 993-1002 (2007).
141. F. Banaz-Yaşar, K. Lennartz, E. Winterhager and A. Gellhaus, Radiation-induced bystander effects in malignant trophoblast cells are independent from gap junctional communication. J. Cell. Biochem. 103, 149-161 (2008).
142. C. Mothersill, F. Lyng, C. Seymour, P. Maguire, S. Lorimore and E. Wright, Genetic factors influencing bystander signaling in murine bladder epithelium after low-dose irradiation in vivo. Radiat. Res. 163, 391-399 (2005). (Pubitemid 40404647)
143. B. I. Gerashchenko and R. W. Howell, Proliferative response of bystander cells adjacent to cells with incorporated radioactivity. Cytometry A 60, 155-164 (2004). (Pubitemid 39079508)
144. M. A. Hill, J. R. Ford, P. Clapham, S. J. Marsden, D. L. Stevens, K. M. Townsend and D. T. Goodhead, Bound PCNA in nuclei of primary rat tracheal epithelial cells after exposure to very low doses of plutonium-238 alpha particles. Radiat. Res. 163, 36-44 (2005). (Pubitemid 40039942)
145. J. L. Schwartz, Variability: the common factor linking low doseinduced genomic instability, adaptation and bystander effects. Mutat. Res. 616, 196-200 (2007). (Pubitemid 46206079)
146. H. Matsumoto, N. Hamada, A. Takahashi, Y. Kobayashi and T. Ohnishi, Vanguards of paradigm shift in radiation biology: radiation-induced adaptive and bystander responses. J. Radiat. Res. (Tokyo) 48, 97-106 (2007). (Pubitemid 46535893)
147. L. Huang, P. M. Kim, J. A. Nickoloff and W. F. Morgan, Targeted and nontargeted effects of low-dose ionizing radiation on delayed genomic instability in human cells. Cancer Res. 67, 1099-1104 (2007).
148. S. R. Moore, D. A. Macdonald and M. A. Kadhim, The contribution of communication between irradiated cells and between bystander cells to clonogenic survival and genomic instability. Int. J. Low Radiat. 3, 201-216 (2006). (Pubitemid 44745952)
149. R. J. Preston, Bystander effects, genomic instability, adaptive response, and cancer risk assessment for radiation and chemical exposures. Toxicol. Appl. Pharmacol. 207, 550-556 (2005).
150. C. Streffer, Bystander effects, adaptive response and genomic instability induced by prenatal irradiation. Mutat. Res. 568, 79-87 (2004). (Pubitemid 39458298)
151. B. R. Scott, A biological-based model that links genomic instability, bystander effects, and adaptive response. Mutat. Res. 568, 129-143 (2004). (Pubitemid 39458303)
152. D. Klokov, T. Criswell, K. S. Leskov, S. Araki, L. Mayo and D. A. Boothman, IR-inducible clusterin gene expression: a protein with potential roles in ionizing radiation-induced adaptive responses, genomic instability, and bystander effects. Mutat. Res. 568, 97-110 (2004). (Pubitemid 39458300)
153. M. A. Kadhim, S. R. Moore and E. H. Goodwin, Interrelationships amongst radiation-induced genomic instability, bystander effects, and the adaptive response. Mutat. Res. 568, 21-32 (2004). (Pubitemid 39458293)
154. W. F. Morgan, Will radiation-induced bystander effects or adaptive responses impact on the shape of the dose response relationships at low doses of ionizing radiation? Dose Response 4, 257-262 (2006).
155. G. E. Watson, S. A. Lorimore, S. M. Clutton, M. A. Kadhim and E. G. Wright, Genetic factors influencing alpha-particleinduced chromosomal instability. Int. J. Radiat. Biol. 71, 497-503 (1997). (Pubitemid 27229746)
156. K. L. Chapman, J. W. Kelly, R. Lee, E. H. Goodwin and M. A. Kadhim, Tracking genomic instability within irradiated and bystander populations. J. Pharm. Pharmacol. 60, 959-968 (2008).
157. D. A. Bowler, S. R. Moore, D. A. Macdonald, S. H. Smyth, P. Clapham and M. A. Kadhim, Bystander-mediated genomic instability after high LET radiation in murine primary haemopoietic stem cells. Mutat. Res. 597, 50-61 (2006).
158. S. A. Lorimore, J. M. McIlrath, P. J. Coates and E. G. Wright, Chromosomal instability in unirradiated hemopoietic cells resulting from a delayed in vivo bystander effect of γ radiation. Cancer Res. 65, 5668-5673 (2005). (Pubitemid 40911168)
159. B. Ponnaiya, G. Jenkins-Baker, A. Bigelow, S. Marino and C. R. Geard, Detection of chromosomal instability in alphairradiated and bystander human fibroblasts. Mutat. Res. 568, 41-48 (2004). (Pubitemid 39458295)
160. M. Pinto, E. I. Azzam and R. W. Howell, Investigation of adaptive responses in bystander cells in 3D cultures containing tritium-labeled and unlabeled normal human fibroblasts. Radiat. Res. 174, 216-227 (2010).
161. H. Klammer, M. Kadhim and G. Iliakis, Evidence of an adaptive response targeting DNA nonhomologous end joining and its transmission to bystander cells. Cancer Res. 70, 8498-8506 (2010).
162. T. K. Day, A. M. Hooker, G. Zeng and P. J. Sykes, Low dose X-radiation adaptive response in spleen and prostate of Atm knockout heterozygous mice. Int. J. Radiat. Biol. 83, 523-534 (2007). (Pubitemid 47035916)
163. T. K. Day, G. Zeng, A. M. Hooker, M. Bhat, B. R. Scott, D. R. Turner and P. J. Sykes, Extremely low priming doses of X-radiation induce an adaptive response for chromosomal inversions in the pKZ1 mouse prostate. Radiat. Res. 166, 757-766 (2006). (Pubitemid 44706612)
164. G. Zeng, T. K. Day, A. M. Hooker, B. J. Blyth, M. Bhat, W. D. Tilley and P. J. Sykes, Non-linear chromosomal inversion response in prostate after low dose X-radiation exposure. Mutat. Res. 602, 65-73 (2006). (Pubitemid 44693555)
165. T. K. Day, G. Zeng, A. M. Hooker, M. Bhat, B. R. Scott, D. R. Turner and P. J. Sykes, Adaptive response for chromosomal inversions in pKZ1 mouse prostate induced by low doses of X radiation delivered after a high dose. Radiat. Res. 167, 682-692 (2007). (Pubitemid 351292948)
166. A. Hooker, M. Bhat, T. Day, J. Lane, S. Swinburne, A. Morley and P. Sykes, The linear no-threshold model does not hold for low-dose ionizing radiation. Radiat. Res. 162, 447-452 (2004). (Pubitemid 39388167)
167. M. B. Sowa, W. Goetz, J. E. Baulch, D. N. Pyles, J. Dziegielewski, S. Yovino, A. R. Snyder, S. M. de Toledo, E. I. Azzam and W. F. Morgan, Lack of evidence for low-LET radiation induced bystander response in normal human fibroblasts and colon carcinoma cells. Int. J. Radiat. Biol. 86, 102-113 (2010).