Bystander effect (radiobiology) explained

The radiation-induced bystander effect (bystander effect) is the phenomenon in which unirradiated cells exhibit irradiated effects as a result of signals received from nearby irradiated cells. In November 1992, Hatsumi Nagasawa and John B. Little first reported this radiobiological phenomenon.[1]

Effect

There is evidence that targeted cytoplasmic irradiation results in mutation in the nucleus of the hit cells.[2] [3] Cells that are not directly hit by an alpha particle, but are in the vicinity of one that is hit, also contribute to the genotoxic response of the cell population.[4] [5] Similarly, when cells are irradiated, and the medium is transferred to unirradiated cells, these unirradiated cells show bystander responses when assayed for clonogenic survival and oncogenic transformation.[6] [7] This is also attributed to the bystander effect.

Demonstration

The demonstration of a bystander effect in 3D human tissues[8] and, more recently, in whole organisms[9] have clear implication of the potential relevance of the non-targeted response to human health.

Consequences

This effect may also contribute to the final biological consequences of exposure to low doses of radiation.[10] [11] However, there is currently insufficient evidence to suggest that the bystander effect promotes carcinogenesis in humans at low doses.[12]

Notes

Note that the bystander effect is not the same as the abscopal effect. The abscopal effect is a phenomenon where the response to radiation is seen in an organ/site distant to the irradiated organ/area, that is, the responding cells are not juxtaposed with the irradiated cells. T-cells and dendritic cells have been implicated to be part of the mechanism.[13]

In suicide gene therapy, the "bystander effect" is the ability of the transfected cells to transfer death signals to neighboring tumor cells.[14]

Notes and References

  1. 1423287. 1992. Nagasawa. H. Induction of sister chromatid exchanges by extremely low doses of alpha-particles. Cancer Research. 52. 22. 6394–6. Little. J. B..
  2. 10220401 . 96 . 9 . Targeted cytoplasmic irradiation with alpha particles induces mutations in mammalian cells . 21799 . April 1999 . Wu LJ, Randers-Pehrson G, Xu A . 4959–64 . Proceedings of the National Academy of Sciences of the United States of America. 1999PNAS...96.4959W . 10.1073/pnas.96.9.4959 . etal. free .
  3. 15070061 . The radiation-induced bystander effect: evidence and significance . 23 . 2 . February 2004 . Azzam EI, Little JB . 61–5 . Human & Experimental Toxicology . 10.1191/0960327104ht418oa. 13030268 . free .
  4. 10681418 . 10.1073/pnas.030420797 . 97 . 5 . Induction of a bystander mutagenic effect of alpha particles in mammalian cells . 15760 . February 2000 . Zhou H, Randers-Pehrson G, Waldren CA, Vannais D, Hall EJ, Hei TK . Proc. Natl. Acad. Sci. U.S.A. . 2099–104. 2000PNAS...97.2099Z . free .
  5. 9881726 . 74 . 6 . Studies of bystander effects in human fibroblasts using a charged particle microbeam . December 1998 . Prise KM, Belyakov OV, Folkard M, Michael BD . 793–8 . International Journal of Radiation Biology . 10.1080/095530098141087.
  6. 15038773 . 161 . 4 . The bystander response in C3H 10T1/2 cells: the influence of cell-to-cell contact . April 2004 . Mitchell SA, Randers-Pehrson G, Brenner DJ, Hall EJ . Radiat. Res. . 397–401 . 10.1667/rr3137. 2004RadR..161..397M . 10.1.1.516.4869 . 14203843 .
  7. 15360084 . 80 . 7 . Bystander effect and adaptive response in C3H 10T(1/2) cells . July 2004 . Mitchell SA, Marino SA, Brenner DJ, Hall EJ . Int. J. Radiat. Biol. . 465–72 . 10.1080/09553000410001725116. 84489110 .
  8. Sedelnikova OA, Nakamura A, Kovalchuk O . DNA double-strand breaks form in bystander cells after microbeam irradiation of three-dimensional human tissue models . Cancer Res. . 67 . 9 . 4295–302 . May 2007 . 17483342 . 10.1158/0008-5472.CAN-06-4442 . etal. free .
  9. 19346684 . 3685624 . 50 Suppl A . Microbeam irradiation of the C. elegans nematode . March 2009 . Bertucci A, Pocock RD, Randers-Pehrson G, Brenner DJ . A49–54 . Journal of Radiation Research . 10.1269/jrr.08132s. 2009JRadR..50A..49B .
  10. 18711141 . 10.1073/pnas.0804186105 . 105 . 34 . Oncogenic bystander radiation effects in Patched heterozygous mouse cerebellum . 2517601 . August 2008 . Mancuso M, Pasquali E, Leonardi S . 12445–50 . Proceedings of the National Academy of Sciences. 2008PNAS..10512445M . etal. free .
  11. 19724078 . 63 . [Radiation-induced bystander effect: the important part of ionizing radiation response. Potential clinical implications] . 2009 . Wideł M, Przybyszewski W, Rzeszowska-Wolny J . 377–88 . Postepy Higieny i Medycyny Doswiadczalnej.
  12. 10.1667/RR2548.1 . 0033-7587 . 176 . 2 . 139–157 . Blyth . Benjamin J. . Pamela J. Sykes . Radiation-Induced Bystander Effects: What Are They, and How Relevant Are They to Human Radiation Exposures? . Radiation Research . 2011 . 21631286 . dead . https://web.archive.org/web/20120323170444/http://lowdose.energy.gov/radiation_bystandereffects.aspx . 2012-03-23 . 2011RadR..176..139B . 38879987 .
  13. 14967443 . 10.1016/j.ijrobp.2003.09.012 . 58 . 3 . Ionizing radiation inhibition of distant untreated tumors (abscopal effect) is immune mediated . March 2004 . Demaria S, Ng B, Devitt ML . 862–70. International Journal of Radiation Oncology, Biology, Physics. etal.
  14. Progress and problems with the use of suicide genes for targeted cancer therapy. Karjoo. Z.. 2015. Advanced Drug Delivery Reviews. 10.1016/j.addr.2015.05.009. 26004498. Chen. X.. A.. Hatefi. 99. Pt A. 4758904. 113–28.

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