Summary
The standard paradigm for radiation effects in biological systems is that direct DNA damage within the nucleus of a cell is required to trigger the down-stream biological consequences. However, significant evidence has been obtained for the presence of bystander effects where cells respond to the fact that their neighbours have been irradiated. As well as extensive evidence from external beam exposures, several studies have reported bystander responses after radionuclide incorporation. These have included the use of 3 H, 121 I, 123 I, 131 I and 211At-labelled targets. Responses have been reported both in vitro and in vivo and are distinct from physical cross-fire effects. For the development of new targeted therapies involving radionuclides, it is clear that bystander responses have the potential to significantly enhance the effectiveness of these approaches if the underlying mechanisms can be fully elucidated.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
R . L. Warters, K. G. Hofer, C. R. Harris and J. M. Smith, Radionuclide toxicity in cultured mammalian cells: elucidation of the primary site of radiation damage. Curr. Top. Radiat. Res. Q. 12, 389-407 (1977).
R . L. Warters and K. G. Hofer, Radionuclide toxicity in cultured mammalian cells. Elucidation of the primary site for radiation-induced division delay. Radiat. Res. 69, 348-358 (1977).
T . R. Munro, The relative radiosensitivity of the nucleus and cytoplasm of Chinese hamster fibroblasts. Radiat. Res. 42, 451-470 (1970).
R . E. Zirkle, Partial-cell irradiation. In Advances in Biology and Medical Physics (J. H. Lawrence and C. A. Tobias, Eds.), pp. 103-146. Academic, New York, 1957.
A. Cole, R. E. Meyn, R. Chen, P. M. Corry and W. Hittelman, Mechanisms of cell injury. In Radiation Biology in Cancer Research (R. E. Meyn and H. R. Withers, Eds.), pp. 33-58. Raven Press, New York, 1980.
E . J. Hall and A. J. Giaccia, Radiobiology for the Radiologist. Lippincott William & Wilkins, Philadelphia, PA, 2006.
J. F. Ward, Non-DNA targeted effects and DNA models. In Radiat. Res. (M. Moriarty, C. Mothersill, C. Seymour, M. Edington, J. F. Ward and R. J. M. Fry, Eds.), pp. 379-402. Allen Press, Lawrence, KS, 2000.
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).
W . F. Morgan, Non-targeted and delayed effects of exposure to ionizing radiation: I. Radiationinduced genomic instability and bystander effects in vitro. Radiat. Res. 159, 567-580 (2003).
S. Tapio and V. Jacob, Radioadaptive response revisited. Radiat. Environ. Biophys. 46, 1-12 (2006).
E. G. Wright and P. J. Coates, Untargeted effects of ionizing radiation: implications for radiation pathology. Mutat. Res. 597, 119-132 (2006).
M. C. Joiner, B. Marples, P. Lambin, S. C. Short and I. Turesson, Low-dose hypersensitivity: current status and possible mechanisms. Int. J. Radiat. Oncol. Biol. Phys. 49, 379-389 (2001).
C. R. Mitchell, M. Folkard and M. C. Joiner, Effects of exposure to low-dose-rate (60)co gamma rays on human tumor cells in vitro. Radiat. Res. 158, 311-318 (2002).
J. G. Hollowell and G. Littlefield, Chromosome damage induced by plasma of x-rayed patients: an indirect effect of x-ray. Proc. Soc. Exp. Biol. Med. 129, 240-244 (1968).
I. Emerit, S. H. Khan and H. Esterbauer, Hydroxynonenal, a component of clastogenic factors? Free Radic. Biol. Med. 10, 371-377 (1991).
C. Auclair, A. Gouyette, A. Levy and I. Emerit, Clastogenic inosine nucleotide as components of the chromosome breakage factor in scleroderma patients. Arch. Biochem. Biophys. 278, 238-244 (1990).
I. Emerit, F. Garban, J. Vassy, A. Levy, P. Filipe and J. Freitas, Superoxide-mediated clastogenesis and anticlastogenic effects of exogenous superoxide dismutase. Proc. Natl. Acad. Sci. USA 93, 12799-12804 (1996).
H. Nagasawa and J. B. Little, induction of sister chromatid exchanges by extremely low doses of α-particles. Cancer Res. 52, 6394-6396 (1992).
C. Mothersill and C. Seymour, Medium from irradiated human epithelial cells but not human fibroblasts reduces the clonogenic survival of irradiated cells. Int. J. Radiat. Biol. 71, 421-427 (1997).
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).
C. Shao, M. Folkard, B. D. Michael and K. M. Prise, Targeted cytoplasmic irradiation induces bystander responses. Proc. Natl. Acad. Sci. USA 101, 13495-13500 (2004).
L. Tartier, S. Gilchrist, S. Burdak-Rothkamm, M. Folkard and K. M. Prise, Cytoplasmic irradiation induces mitochondrial-dependent 53BP1 protein relocalization in irradiated and bystander cells. Cancer Res. 67, 5872-5879 (2007).
L. J. Wu, G. Randers-Pehrson, A. Xu, C. A. Waldren, C. R. Geard, Z. Yu and T. K. Hei, Targeted cytoplasmic irradiation with alpha particles induces mutations in mammalian cells. Proc. Natl. Acad. Sci. USA 96, 4959-4964 (1999).
O. V. 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).
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).
M. A. Khan, R. P. Hill and J. Van Dyk, Partial volume rat lung irradiation: an evaluation of early DNA damage. Int. J. Radiat. Oncol. Biol. Phys. 40, 467-476 (1998).
I. Koturbash, R. E. Rugo, C. A. Hendricks, J. Loree, B. Thibault, K. Kutanzi, I. Pogribny, J. C. Yanch, B. P. Engelward and O. Kovalchuk, Irradiation induces DNA damage and modulates epigenetic effectors in distant bystander tissue in vivo. Oncogene 25, 4267-4275 (2006).
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).
K. M. Prise, O. V. 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).
H. Yang, N. Asaad and K. D. Held, Medium-mediated intercellular communication is involved in bystander responses of X-ray-irradiated normal human fibroblasts. Oncogene (2005).
A. Bishayee, D. V. Rao and R. W. Howell, Evidence for pronounced bystander effects caused by nonuniform distributions of radioactivity using a novel three-dimensional tissue culture model. Radiat. Res. 152, 88-97 (1999).
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, 1-10 (2000).
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).
B. I. Gerashchenko and R. W. Howell, Proliferative response of bystander cells adjacent to cells with incorporated radioactivity. Cytometry A 60, 155-164 (2004).
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).
R. Persaud, H. Zhou, T. K. Hei and E. J. Hall, Demonstration of a radiation-induced bystander effect for low dose low LET beta-particles. Radiat. Environ. Biophys. 46, 395-400 (2007).
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).
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 alpha-, beta-, and auger electron-emitting radionuclides. J. Nucl. Med. 47, 1007- 1015 (2006).
J. L. Dearling and R. B. Pedley, Technological advances in radioimmunotherapy. Clin. Oncol. (Royal College of Radiologists (Great Britain) ) 19, 457-469 (2007).
S. J. DeNardo and G. L. Denardo, Targeted radionuclide therapy for solid tumors: an overview. Int. J. Radiat. Oncol., Biol., Phys. 66, S89-95 (2006).
M. Boyd, S. H. Cunningham, M. M. Brown, R. J. Mairs and T. E. Wheldon, Noradrenaline transporter gene transfer for radiation cell kill by 131I meta-iodobenzylguanidine. Gene Ther. 6, 1147-1152 (1999).
C. A. Boswell and M. W. Brechbiel, Development of radioimmunotherapeutic and diagnostic antibodies: an inside-out view. Nucl. Med. Biol. 34, 757-778 (2007).
D. J. Brenner, R. Doll, D. T. Goodhead, E. J. Hall, C. E. Land, J. B. Little, J. H. Lubin, D. L. Preston, R. J. Preston, et al., Cancer risks attributable to low doses of ionizing radiation: assessing what we really know. Proc. Natl. Acad. Sci. USA 100, 13761-13766 (2003).
E. J. Hall, Intensity-modulated radiation therapy, protons, and the risk of second cancers. Int. J. Radiat. Oncol. Biol. Phys. 65, 1-7 (2006).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Springer Science + Business Media B.V
About this chapter
Cite this chapter
Prise, K.M. (2008). Bystander Effects and Radionuclide Therapy. In: Stigbrand, T., Carlsson, J., Adams, G.P. (eds) Targeted Radionuclide Tumor Therapy. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-8696-0_17
Download citation
DOI: https://doi.org/10.1007/978-1-4020-8696-0_17
Publisher Name: Springer, Dordrecht
Print ISBN: 978-1-4020-8695-3
Online ISBN: 978-1-4020-8696-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)