Abstract
The paradigm of genetic alterations being restricted to direct DNA damage after exposure to ionizing radiation has been challenged by observations in which cells that are not exposed to ionizing radiation exhibit responses typically associated with direct radiation exposure. These effects are demonstrated in cells that are the descendants of irradiated cells (radiation-induced genomic instability) or in cells that are in contact with irradiated cells or receive certain signals from irradiated cells (radiation-induced bystander effects). There is accumulating evidence that radiation-induced genomic instability may be a consequence of, and in some cell systems may also produce, bystander interactions involving intercellular signalling, production of cytokines and free-radical generation. These processes are also features of inflammatory responses that are known to have the potential for both bystander-mediated and persisting damage as well as for conferring a predisposition to malignancy. Thus, radiation-induced genomic instability and untargeted bystander effects may reflect inter-related aspects of inflammatory-type responses to radiation-induced stress and injury and contribute to the variety of pathological consequences of radiation exposures.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 50 print issues and online access
$259.00 per year
only $5.18 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Auclair C, Gouyette A, Levy A and Emerit I . (1990). Arch. Biochem. Biophys., 278, 238–244.
Azzam EI, de Toledo SM, Gooding T and Little JB . (1998). Radiat. Res., 150, 497–504.
Azzam EI, de Toledo SM and Little JB . (2001). Proc. Natl. Acad. Sci. USA, 98, 473–478.
Babior BM . (1984). Blood, 64, 959–966.
Babior BM . (2000). Am. J. Med., 109, 33–44.
Barlow C, Brown KD, Deng CX, Tagle DA and Wynshaw-Boris A . (1997). Nat. Genet., 17, 453–456.
Belyakov OV, Folkard M, Mothersill C, Prise KM and Michael BD . (2002). Radiat. Prot. Dosimetry, 99, 249–251.
Belyakov OV, Folkard M, Mothersill C, Prise KM and Michael BD . (2003). Br. J. Cancer, 88, 767–774.
Belyakov OV, Malcolmson AM, Folkard M, Prise KM and Michael BD . (2001). Br. J. Cancer, 84, 674–679.
Belyakov OV, Prise KM, Trott KR and Michael BD . (1999). Int. J. Radiat. Biol., 75, 985–993.
Birnboim HC . (1982). Science, 215, 1247–1249.
Bouvard V, Zaitchouk T, Vacher M, Duthu A, Canivet M, Choisy-Rossi C, Nieruchalski M and May E . (2000). Oncogene, 19, 649–660.
Brenner DJ and Hall EJ . (2002). Radiat. Prot. Dosimetry, 99, 283–286.
Brockhaus F and Brune B . (1999). Oncogene, 18, 6403–6410.
Brown DC and Trott KR . (1994). Int. J. Radiat. Biol., 66, 151–155.
Brune B, Golkel C and von Knethen A . (1996). Biochem. Biophys. Res. Commun., 229, 396–401.
Burns TF, Bernhard EJ and El-Deiry WS . (2001). Oncogene, 20, 4601–4612.
Chance B, Sies H and Boveris A . (1979). Physiol. Rev., 59, 527–605.
Chang WP and Little JB . (1992). Mutat. Res., 270, 191–199.
Chiba S, Saito A, Ogawa S, Takeuchi K, Kumano K, Seo S, Suzuki T, Tanaka Y, Saito T, Izutsu K, Yuji K, Masuda S, Futami S, Nishida M, Suzuki G, Gale RP, Fukayama M, Maekawa K and Hirai H . (2002). Bone Marrow Transplantation, 29, 935–939.
Clutton SM, Townsend KM, Walker C, Ansell JD and Wright EG . (1996a). Carcinogenesis, 17, 1633–1639.
Clutton SM, Townsend KMS, Goodhead DT, Ansell JA and Wright EG . (1996b). Cell Death Differ., 3, 141–148.
Coates PJ, Lorimore SA, Lindsay K and Wright EG . (2003). J. Pathol.. in press.
Coen N, Mothersill C, Kadhim M and Wright EG . (2001). J. Pathol., 195, 293–299.
Darveau R . (1999). Nat. Biotechnol., 17, 19.
Deshpande A, Goodwin EH, Bailey SM, Marrone BL and Lehnert BE . (1996). Radiat. Res., 145, 260–267.
Dizdaroglu M, Olinski R, Doroshow JH and Akman SA . (1993). Cancer Res., 53, 1269–1272.
Durocher D and Jackson SP . (2001). Curr. Opin. Cell Biol., 13, 225–231.
Elkind M and Sutton H . (1959). Nature, 184, 1293–1295.
Emerit I . (1990). Methods Enzymol., 186, 555–564.
Emerit I . (1994). Free Radic. Biol. Med., 16, 99–109.
Emerit I, Khan SH and Esterbauer H . (1991). Free Radic. Biol. Med., 10, 371–377.
Emerit I, Levy A, Cernjavski L, Arutyunyan R, Oganesyan N, Pogosian A, Mejlumian H, Sarkisian T, Gulkandanian M, Quastel M, Goldsmith J and Riklis E . (1994). J. Cancer Res. Clin. Oncol., 120, 558–561.
Emerit I, Levy A, Pagano G, Pinto L, Calzone R and Zatterale A . (1995). Human Genet., 96, 14–20.
Emerit I, Oganesian N, Arutyunian R, Pogossian A, Sarkisian T, Cernjavski L, Levy A and Feingold J . (1997). Mutat. Res., 377, 239–246.
Fei P, Bernhard EJ and El-Deiry WS . (2002). Cancer Res., 62, 7316–7327.
Futaki M and Liu JM . (2001). Trends Mol. Med., 7, 560–565.
Giles KM, Hart SP, Haslett C, Rossi AG and Dransfield I . (2000). Br. J. Haematol., 109, 1–12.
Goh K and Sumner H . (1968). Radiat. Res., 35, 171–181.
Gorgojo L and Little JB . (1989). Int. J. Radiat. Biol., 55, 619–630.
Gorospe M, Cirielli C, Wang X, Seth P, Capogrossi MC and Holbrook NJ . (1997). Oncogene, 14, 929–935.
Gregory CD . (2000). Curr. Opin. Immunol., 12, 27–34.
Grosovsky AJ, Parks KK, Giver CR and Nelson SL . (1996). Mol. Cell Biol., 16, 6252–6262.
Hall EJ . (2001). Phys. Med., 17, 21–25.
Harper K, Lorimore SA and Wright EG . (1997). Exp. Hematol., 25, 263–269.
Hayashi T, Kusunoki Y, Hakoda M, Morishita Y, Kubo Y, Maki M, Kasagi F, Kodama K, Macphee DG and Kyoizumi S . (2003). Int. J. Radiat. Biol., 79, 129–136.
Hibner U and Coutinho A . (1994). Cell Death Differ., 1, 33–37.
Hickman AW, Jaramillo RJ, Lechner JF and Johnson NF . (1994). Cancer Res., 54, 5797–5800.
Hollowell JG and Littlefield LG . (1967). J. SC Med. Assoc., 63, 437–442.
Holmberg K, Meijer AE, Auer G and Lambert BO . (1995). Int. J. Radiat. Biol., 68, 245–255.
Holmberg K, Meijer AE, Harms-Ringdahl M and Lambert B . (1998). Int. J. Radiat. Biol., 73, 21–34.
Ishikawa Y, Wada I and Fukumoto M . (2001). J. Environ. Pathol. Toxicol. Oncol., 20, 311–315.
Iwamoto KS, Fujii S, Kurata A, Suzuki M, Hayashi T, Ohtsuki Y, Okada Y, Narita M, Takahashi M, Hosobe S, Doishita K, Manabe T, Hata S, Murakami I, Itoyama S, Akatsuka S, Ohara N, Iwasaki K, Akabane H, Fujihara M, Seyama T and Mori T . (1999). Carcinogenesis, 20, 1283–1291.
Iyer R and Lehnert BE . (2000). Cancer Res., 60, 1290–1298.
Kadhim MA . (2002). Bystander mediated genomic instability of individual radiation track. Abstracts of the Forty-ninth Annual Meeting of the Radiation Research Society: Oak Brook, IL, USA, P.84.
Kadhim MA, Lorimore SA, Hepburn MD, Goodhead DT, Buckle VJ and Wright EG . (1994). Lancet, 344, 987–988.
Kadhim MA, Macdonald DA, Goodhead DT, Lorimore SA, Marsden SJ and Wright EG . (1992). Nature, 355, 738–740.
Kadhim MA, Marsden SJ, Goodhead DT, Malcolmson AM, Folkard M, Prise KM and Michael BD . (2001). Radiat. Res., 155, 122–126.
Knudsen LE, Loft SH and Autrup H . (2001). Mutat. Res., 482, 83–88.
Lefevre SH, Vogt N, Dutrillaux AM, Chauveinc L, Stoppa-Lyonnet D, Doz F, Desjardins L, Dutrillaux B, Chevillard S and Malfoy B . (2001). Oncogene, 20, 8092–8099.
Lehnert BE and Goodwin EH . (1997a). Cancer Res., 57, 2164–2171.
Lehnert BE and Goodwin EH . (1997b). Environon. Health Perspect., 105 (Suppl. 5), 1095–1101.
Li CY, Yandell DW and Little JB . (1992). Mol. Carcinogen., 5, 270–277.
Li CY, Yandell DW and Little JB . (1994). Mol. Cell Biol., 14, 4373–4379.
Limoli CL, Day JP, Ward JF and Morgan WF . (1998a). Photochem. Photobiol., 67, 233–238.
Limoli CL, Hartmann A, Shephard L, Yang CR, Boothman DA, Bartholomew J and Morgan WF . (1998b). Cancer Res., 58, 3712–3718.
Limoli CL, Kaplan MI, Giedzinski E and Morgan WF . (2001). Free Radic. Biol. Med., 31, 10–19.
Limoli CL, Kaplan MI, Phillips JW, Adair GM and Morgan WF . (1997). Cancer Res., 57, 4048–4056.
Little JB . (1998). Int. J. Radiat. Biol., 74, 663–671.
Little JB . (2000). Carcinogenesis, 21, 397–404.
Little JB, Gorgojo L and Vetrovs H . (1990). Int. Radiat. Oncol. Biol. Phys., 19, 1425–1429.
Little JB, Nagasawa H, Pfenning T and Vetrovs H . (1997). Radiat. Res., 148, 299–307.
Littlefield LG, Hollowell Jr JG and Pool Jr WH . (1969). Radiology, 93, 879–886.
Lloyd DC and Moquet JE . (1985). Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med., 47, 433–444.
Lorimore SA, Coates PJ, Scobie GE, Milne G and Wright EG . (2001). Oncogene, 20, 7085–7095.
Lorimore SA, Kadhim MA, Pocock DA, Papworth D, Stevens DL, Goodhead DT and Wright EG . (1998). Proc. Natl. Acad. Sci. USA, 95, 5730–5733.
Lorimore SA and Wright EG . (2003). Int. J. Radiat. Biol., 79, 15–25.
Lyng FM, Seymour CB and Mothersill C . (2000). Br. J. Cancer, 83, 1223–1230.
Lyng FM, Seymour CB and Mothersill C . (2002). Radiat. Res., 157, 365–370.
Maeda H and Akaike T . (1998). Biochemistry (Moscow), 63, 854–865.
Marder BA and Morgan WF . (1993). Mol. Cell Biol., 13, 6667–6677.
Meyn MS . (1997). Curr. Top Microbiol. Immunol., 221, 71–148.
Mohrenweiser HW and Jones IM . (2000). Radiat. Res., 154, 722–723, discussion 723–724.
Morgan WF, Hartmann A, Limoli CL, Nagar S and Ponnaiya B . (2002). Mutat. Res., 504, 91–100.
Mothersill C, Crean M, Lyons M, McSweeney J, Mooney R, O'Reilly J and Seymour CB . (1998). Int. J. Radiat. Biol., 74, 673–680.
Mothersill C, Kadhim MA, O'Reilly S, Papworth D, Marsden SJ, Seymour CB and Wright EG . (2000a). Int. J. Radiat. Biol., 76, 799–806.
Mothersill C, Rea D, Wright EG, Lorimore SA, Murphy D, Seymour CB and O'Malley K . (2001). Carcinogenesis, 22, 1465–1471.
Mothersill C and Seymour C . (1997). Int. J. Radiat. Biol., 71, 421–427.
Mothersill C and Seymour CB . (1998). Radiat. Res., 149, 256–262.
Mothersill C and Seymour C . (2000). Radiat. Biol. Radioecol., 40, 615–620.
Mothersill C, Stamato TD, Perez ML, Cummins R, Mooney R and Seymour CB . (2000b). Br. J. Cancer, 82, 1740–1746.
Mothersill CE, O'Malley KJ, Murphy DM, Seymour CB, Lorimore SA and Wright EG . (1999). Carcinogenesis, 20, 2273–2278.
Nagar S, Smith LE and Morgan WF . (2003). Cancer Res., 63, 324–328.
Nagasawa H and Little JB . (1992). Cancer Res., 52, 6394–6396.
Nagasawa H and Little JB . (1999). Radiat. Res., 152, 552–557.
Narayanan PK, Goodwin EH and Lehnert BE . (1997). Cancer Res., 57, 3963–3971.
Nathan C and Shiloh MU . (2000). Proc. Natl. Acad. Sci. USA, 97, 8841–8848.
Nebert DW . (2000). Clin. Chem. Lab. Med., 38, 857–861.
Neriishi K, Nakashima E and Delongchamp RR . (2001). Int. J. Radiat. Biol., 77, 475–482.
Pampfer S and Streffer C . (1989). Int. J. Radiat. Biol., 55, 85–92.
Pant GS and Kamada N . (1977). Hiroshima J. Med. Sci., 26, 149–154.
Parchment RE and Natarajan K . (1992). Cytotechnology, 10, 93–124.
Parsons WB, Watkins CH, Pease GL and Childs DS . (1954). Cancer Genet. Cytogenet., 7, 179–189.
Pharoah PD, Antoniou A, Bobrow M, Zimmern RL, Easton DF and Ponder BA . (2002). Nat. Genet., 31, 33–36.
Phillipson RP, Tobi SE, Morris JA and McMillan TJ . (2002). Free Radic. Biol. Med., 32, 474–480.
Ponnaiya B, Cornforth MN and Ullrich RL . (1997). Radiat. Res., 147, 121–125.
Prise KM, Belyakov OV, Folkard M and Michael BD . (1998). Int. J. Radiat. Biol., 74, 793–798.
Puck T and Marcus P . (1956). J. Exp. Med., 103, 653–666.
Rich T, Allen RL and Wyllie AH . (2000). Nature, 407, 777–783.
Rosin MP, Anwar WA and Ward AJ . (1994). Cancer Res., 54, 1929s–1933s.
Scott D . (1969). Cell Tissue Kinet., 2, 295–305.
Seymour C and Mothersill C . (1992). Mutat. Res., 267, 19–30.
Seymour CB and Mothersill C . (2000). Radiat. Res., 153, 508–511.
Seymour CB, Mothersill C and Alper T . (1986). Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med., 50, 167–179.
Shacter E, Beecham EJ, Covey JM, Kohn KW and Potter M . (1988). Carcinogenesis, 9, 2297–2304.
Shiloh Y . (2001). Curr. Opin. Genet. Dev., 11, 71–77.
Simons JW . (1995). Crit. Rev. Rev. Oncogenesis, 6, 261–273.
Tappel AL . (1973). Fed. Proc., 32, 1870–1874.
Thompson LH and Suit HD . (1969). Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med., 15, 347–362.
Trott KR and Hug O . (1970). Int. J. Radiat. Biol. Relat. Stud. Phys. Chem. Med., 17, 483–486.
Uchimura E, Watanabe N, Niwa O, Muto M and Kobayashi Y . (2000). J. Leukocyte Biol., 67, 780–784.
Ullrich RL and Ponnaiya B . (1998). Int. J. Radiat. Biol., 74, 747–754.
Wallace M, Coates PJ, Wright EG and Ball KL . (2001). Oncogene, 20, 3597–3608.
Wang S, Guo M, Ouyang H, Li X, Cordon-Cardo C, Kurimasa A, Chen DJ, Fuks Z, Ling CC and Li GC . (2000). Proc. Natl. Acad. Sci. USA, 97, 1584–1588.
Watson GE, Lorimore SA, Clutton SM, Kadhim MA and Wright EG . (1997). Int. J. Radiat. Biol., 71, 497–503.
Watson GE, Lorimore SA, Macdonald DA and Wright EG . (2000). Cancer Res., 60, 5608–5611.
Watson GE, Lorimore SA and Wright EG . (1996). Int. J. Radiat. Biol., 69, 175–182.
Watson GE, Pocock DA, Papworth D, Lorimore SA and Wright EG . (2001). Int. J. Radiat. Biol., 77, 409–417.
Weitberg AB, Weitzman SA, Destrempes M, Latt SA and Stossel TP . (1983). N. Engl. J. Med., 308, 26–30.
Weitzman SA and Gordon LI . (1990). Blood, 76, 655–663.
Weitzman SA and Stossel TP . (1981). Science, 212, 546–547.
Wright EG . (1999). J. Pathol., 187, 19–27.
Wright EG . (2002). Radiation and Homeostasis: International Congress Series. Vol. 1236. Sugahara T, Nikaido O and Niwa O (eds). Elsevier: Amsterdam, pp. 271–281.
Wu LJ, Randers-Pehrson G, Xu A, Waldren CA, Geard CR, Yu Z and Hei TK . (1999). Proc. Natl. Acad. Sci. USA, 96, 4959–4964.
Yu J, Zhang L, Hwang PM, Rago C, Kinzler KW and Vogelstein B . (1999). Proc. Natl. Acad. Sci. USA, 96, 14517–14522.
Zhou BB and Elledge SJ . (2000). Nature, 408, 433–439.
Zhou H, Randers-Pehrson G, Waldren CA, Vannais D, Hall EJ and Hei TK . (2000). Proc. Natl. Acad. Sci. USA, 97, 2099–2104.
Zhou H, Suzuki M, Randers-Pehrson G, Vannais D, Chen G, Trosko JE, Waldren CA and Hei TK . (2001). Proc. Natl. Acad. Sci. USA, 98, 14410–14415.
Acknowledgements
The research in the authors' laboratories is supported by the Medical Research Council, The Leukaemia Research Fund and the Department of Health.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Lorimore, S., Coates, P. & Wright, E. Radiation-induced genomic instability and bystander effects: inter-related nontargeted effects of exposure to ionizing radiation. Oncogene 22, 7058–7069 (2003). https://doi.org/10.1038/sj.onc.1207044
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.onc.1207044
Keywords
This article is cited by
-
VEGF affects mitochondrial ROS generation in glioma cells and acts as a radioresistance factor
Radiation and Environmental Biophysics (2023)
-
NADPH oxidases: new actors in thyroid cancer?
Nature Reviews Endocrinology (2016)
-
Increased risk of second primary malignancies following uterine cancer: a population-based study in Taiwan over a 30-year period
BMC Cancer (2015)
-
Expression of blood serum proteins and lymphocyte differentiation clusters after chronic occupational exposure to ionizing radiation
Radiation and Environmental Biophysics (2014)
-
The Fukushima nuclear accident and the pale grass blue butterfly: evaluating biological effects of long-term low-dose exposures
BMC Evolutionary Biology (2013)