Advertisement

Bystander Effects and Radionuclide Therapy

  • Kevin M. Prise

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.

Keywords

Bystander Effect Radionuclide Therapy Clonogenic Survival Bystander Cell Multicellular Spheroid 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    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).Google Scholar
  2. 2.
    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).CrossRefPubMedGoogle Scholar
  3. 3.
    T . R. Munro, The relative radiosensitivity of the nucleus and cytoplasm of Chinese hamster fibroblasts. Radiat. Res. 42, 451-470 (1970).CrossRefPubMedGoogle Scholar
  4. 4.
    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.Google Scholar
  5. 5.
    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.Google Scholar
  6. 6.
    E . J. Hall and A. J. Giaccia, Radiobiology for the Radiologist. Lippincott William & Wilkins, Philadelphia, PA, 2006.Google Scholar
  7. 7.
    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.Google Scholar
  8. 8.
    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).CrossRefPubMedGoogle Scholar
  9. 9.
    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).CrossRefPubMedGoogle Scholar
  10. 10.
    S. Tapio and V. Jacob, Radioadaptive response revisited. Radiat. Environ. Biophys. 46, 1-12 (2006).CrossRefPubMedGoogle Scholar
  11. 11.
    E. G. Wright and P. J. Coates, Untargeted effects of ionizing radiation: implications for radiation pathology. Mutat. Res. 597, 119-132 (2006).PubMedGoogle Scholar
  12. 12.
    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).CrossRefPubMedGoogle Scholar
  13. 13.
    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).CrossRefPubMedGoogle Scholar
  14. 14.
    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).PubMedGoogle Scholar
  15. 15.
    I. Emerit, S. H. Khan and H. Esterbauer, Hydroxynonenal, a component of clastogenic factors? Free Radic. Biol. Med. 10, 371-377 (1991).Google Scholar
  16. 16.
    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).CrossRefPubMedGoogle Scholar
  17. 17.
    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).CrossRefPubMedGoogle Scholar
  18. 18.
    H. Nagasawa and J. B. Little, induction of sister chromatid exchanges by extremely low doses of α-particles. Cancer Res. 52, 6394-6396 (1992).PubMedGoogle Scholar
  19. 19.
    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).CrossRefPubMedGoogle Scholar
  20. 20.
    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).CrossRefPubMedGoogle Scholar
  21. 21.
    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).CrossRefPubMedGoogle Scholar
  22. 22.
    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).CrossRefPubMedGoogle Scholar
  23. 23.
    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).CrossRefPubMedGoogle Scholar
  24. 24.
    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).CrossRefPubMedGoogle Scholar
  25. 25.
    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).CrossRefPubMedGoogle Scholar
  26. 26.
    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).PubMedGoogle Scholar
  27. 27.
    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).CrossRefPubMedGoogle Scholar
  28. 28.
    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).Google Scholar
  29. 29.
    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).CrossRefPubMedGoogle Scholar
  30. 30.
    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).Google Scholar
  31. 31.
    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).CrossRefPubMedGoogle Scholar
  32. 32.
    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).Google Scholar
  33. 33.
    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).PubMedGoogle Scholar
  34. 34.
    B. I. Gerashchenko and R. W. Howell, Proliferative response of bystander cells adjacent to cells with incorporated radioactivity. Cytometry A 60, 155-164 (2004).CrossRefPubMedGoogle Scholar
  35. 35.
    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).CrossRefPubMedGoogle Scholar
  36. 36.
    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).CrossRefPubMedGoogle Scholar
  37. 37.
    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).CrossRefPubMedGoogle Scholar
  38. 38.
    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).PubMedGoogle Scholar
  39. 39.
    J. L. Dearling and R. B. Pedley, Technological advances in radioimmunotherapy. Clin. Oncol. (Royal College of Radiologists (Great Britain) ) 19, 457-469 (2007).Google Scholar
  40. 40.
    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).Google Scholar
  41. 41.
    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).CrossRefPubMedGoogle Scholar
  42. 42.
    C. A. Boswell and M. W. Brechbiel, Development of radioimmunotherapeutic and diagnostic antibodies: an inside-out view. Nucl. Med. Biol. 34, 757-778 (2007).CrossRefPubMedGoogle Scholar
  43. 43.
    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).CrossRefPubMedGoogle Scholar
  44. 44.
    E. J. Hall, Intensity-modulated radiation therapy, protons, and the risk of second cancers. Int. J. Radiat. Oncol. Biol. Phys. 65, 1-7 (2006).PubMedGoogle Scholar

Copyright information

© Springer Science + Business Media B.V 2008

Authors and Affiliations

  • Kevin M. Prise
    • 1
  1. 1.Centre for Cancer Research and Cell BiologyQueen’s University BelfastBelfastUK

Personalised recommendations