Bystander effect (radiobiology)

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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]

There is evidence[2][3] that targeted cytoplasmic irradiation results in mutation in the nucleus of the hit cells. 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.

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.

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 at hand to suggest that the bystander effect promotes carcinogenesis in humans at low doses.[12]

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]


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