Radiation and Environmental Biophysics

, Volume 52, Issue 3, pp 293–298 | Cite as

Uncomfortable issues in radiation protection posed by low-dose radiobiology

Controversial Issue

Abstract

This paper aims to stimulate discussion about the relevance for radiation protection of recent findings in low-dose radiobiology. Issues are raised which suggest that low-dose effects are much more complex than has been previously assumed. These include genomic instability, bystander effects, multiple stressor exposures and chronic exposures. To date, these have been accepted as being relevant issues, but there is no clear way to integrate knowledge about these effects into the existing radiation protection framework. A further issue which might actually lead to some fruitful approaches for human radiation protection is the need to develop a new framework for protecting non-human biota. The brainstorming that is being applied to develop effective and practical ways to protect ecosystems widens the debate from the narrow focus of human protection which is currently about protecting humans from radiation-induced cancers.

Keywords

Radiation protection Non-targeted effects Chronic radiation exposures Non-human biota 

References

  1. Adam-Guillermin C, Pereira S, Della-Vedova C, Hinton T, Garnier-Laplace J (2012) Genotoxic and reprotoxic effects of tritium and external gamma irradiation on aquatic animals. Rev Environ Contam Toxicol 220:67–103CrossRefGoogle Scholar
  2. Andersson P, Garnier-Laplace J, Beresford NA, Copplestone D, Howard BJ, Howe P, Oughton D, Whitehouse P (2009) Protection of the environment from ionising radiation in a regulatory context (protect): proposed numerical benchmark values. J Environ Radioact 100:1100–1108CrossRefGoogle Scholar
  3. Audette-Stuart M, Kim SB, McMullin D, Festarini A, Yankovich TL, Carr J, Mulpuru S (2011) Adaptive response in frogs chronically exposed to low doses of ionizing radiation in the environment. J Environ Radioact 102:566–573CrossRefGoogle Scholar
  4. Balogh A, Persa E, Bogdándi EN, Benedek A, Hegyesi H, Sáfrány G, Lumniczky K (2013) The effect of ionizing radiation on the homeostasis and functional integrity of murine splenic regulatory T cells. Inflamm Res 62(2):201–212Google Scholar
  5. Brèchignac F, Doi M (2009) Challenging the current strategy of radiological protection of the environment: arguments for an ecosystem approach. J Environ Radioact 100:1125–1134CrossRefGoogle Scholar
  6. Brooks AL (2011) Is a dose dose-rate effectiveness factor (DDREF) needed following exposure to low total radiation doses delivered at low dose-rates? Health Phys 100:262CrossRefGoogle Scholar
  7. Brooks AL, Eberlein PE, Couch LA, Boecker BB (2009) The role of dose-rate on risk from internally-deposited radionuclides and the potential need to separate dose-rate effectiveness factor (DREF) from the dose and dose-rate effectiveness factor (DDREF). Health Phys 97:458–469CrossRefGoogle Scholar
  8. Calabrese V, Cornelius C, Dinkova-Kostova AT, Iavicoli I, Di Paola R, Koverech A, Cuzzocrea S, Rizzarelli E, Calabrese EJ (2012) Cellular stress responses, hormetic phytochemicals and vitagenes in aging and longevity. Biochim Biophys Acta 1822:753–783CrossRefGoogle Scholar
  9. Coen N, Mothersill C, Kadhim M, Wright EG (2001) Heavy metals of relevance to human health induce genomic instability. J Pathol 195:293–299CrossRefGoogle Scholar
  10. Coen N, Kadhim MA, Wright EG, Case CP, Mothersill CE (2003) Particulate debris from a titanium metal prosthesis induces genomic instability in primary human fibroblast cells. Br J Cancer 88:548–552CrossRefGoogle Scholar
  11. Das B, Saini D, Seshadri M (2012) No evidence of telomere length attrition in newborns from high level natural background radiation areas in Kerala coast, south west India. Int J Radiat Biol 88:642–647CrossRefGoogle Scholar
  12. Foo SA, Dworjanyn SA, Poore AG, Byrne M (2012) Adaptive capacity of the habitat modifying sea urchin Centrostephanus rodgersii to ocean warming and ocean acidification: performance of early embryos. PLoS One 7:e42497ADSCrossRefGoogle Scholar
  13. Frank JP, Williams JR (1982) X-ray induction of persistent hypersensitivity to mutation. Science 216:307–308ADSCrossRefGoogle Scholar
  14. Glaholt SP, Chen CY, Demidenko E, Bugge DM, Folt CL, Shaw JR (2012) Adaptive iterative design (AID): a novel approach for evaluating the interactive effects of multiple stressors on aquatic organisms. Sci Total Environ 432:57–64CrossRefGoogle Scholar
  15. Goodhead DT (2006) Energy deposition stochastics and track structure: what about the target? Radiat Prot Dosim 122:3–15CrossRefGoogle Scholar
  16. Goodhead DT (2011) Panel discussion: do non-targeted effects impact the relation between microdosimetry and risk? Radiat Prot Dosim 143:554–556CrossRefGoogle Scholar
  17. Gow MD, Seymour CB, Byun SH, Mothersill CE (2008) Effect of dose rate on the radiation-induced bystander response. Phys Med Biol 53:119–132CrossRefGoogle Scholar
  18. Groesser T, Chun E, Rydberg B (2007) Relative biological effectiveness of high-energy iron ions for micronucleus formation at low doses. Radiat Res 168:675–682CrossRefGoogle Scholar
  19. Higley KA, Kocher DC, Real AG, Chambers DB (2012) Relative biological effectiveness and radiation weighting factors in the context of animals and plants. Ann ICRP 41:233–245CrossRefGoogle Scholar
  20. Joiner MC, Lambin P, Malaise EP, Robson T, Arrand JE, Skov KA, Marples B (1996) Hypersensitivity to very-low single radiation doses: its relationship to the adaptive response and induced radioresistance. Mutat Res 358:171–183CrossRefGoogle Scholar
  21. Kadhim MA, Macdonald DA, Goodhead DT, Lorimore SA, Marsden SJ, Wright EG (1992) Transmission of chromosomal instability after plutonium alpha-particle irradiation. Nature 355:738–740ADSCrossRefGoogle Scholar
  22. Kadhim MA, Lorimore SA, Hepburn MD, Goodhead DT, Buckle VJ, Wright EG (1994) Alpha-particle-induced chromosomal instability in human bone marrow cells. Lancet 344:987–988CrossRefGoogle Scholar
  23. Kalanxhi E, Dahle J (2012) Genome-wide microarray analysis of human fibroblasts in response to γ radiation and the radiation-induced bystander effect. Radiat Res 177:35–43CrossRefGoogle Scholar
  24. Klammer H, Zhang LH, Kadhim M, Iliakis G (2012) Dependence of adaptive response and its bystander transmission on the genetic background of tested cells. Int J Radiat Biol 88:720–726CrossRefGoogle Scholar
  25. Kolesnikova IS, Vorobtsova IE (2011) Radiation-induced “bystander effect” revealed by means of adaptive response in cocultured lymphocytes from humans of different genders. Radiats Biol Radioecol 51:542–548Google Scholar
  26. Larsson CM (2012) Biological basis for protection of the environment. Ann IRCP 41:208–217Google Scholar
  27. Lett JT, Cox AB, Bergtold DS (1986) Cellular and tissue responses to heavy ions: basic considerations. Radiat Environ Biophys 25:1–12CrossRefGoogle Scholar
  28. Little MP (2010) Do non-targeted effects increase or decrease low dose risk in relation to the linear-non-threshold (LNT) model? Mutat Res 687:17–27CrossRefGoogle Scholar
  29. Liu Z, Mothersill CE, McNeill FE, Lyng FM, Byun SH, Seymour CB, Prestwich WV (2006) A dose threshold for a medium transfer bystander effect for a human skin cell line. Radiat Res 166:19–23CrossRefGoogle Scholar
  30. Maguire P, Mothersill C, McClean B, Seymour C, Lyng FM (2007) Modulation of radiation responses by pre-exposure to irradiated cell conditioned medium. Radiat Res 167:485–492CrossRefGoogle Scholar
  31. Manda K, Glasow A, Paape D, Hildebrandt G (2012) Effects of ionizing radiation on the immune system with special emphasis on the interaction of dendritic and T cells. Front Oncol 2:(article 102)Google Scholar
  32. Mason AJ, Giusti V, Green S, Munck AF, Rosenschöld P, Beynon TD, Hopewell JW (2011) Interaction between the biological effects of high- and low-LET radiation dose components in a mixed field exposure. Int J Radiat Biol 87:1162–1172CrossRefGoogle Scholar
  33. McAllister KA, Lorimore SA, Wright EG, Coates PJ (2012) In vivo interactions between ionizing radiation, inflammation and chemical carcinogens identified by increased DNA damage responses. Radiat Res 177:584–593CrossRefGoogle Scholar
  34. Meeks HN, Chesser RK, Rodgers BE, Gaschak S, Baker RJ (2009) Understanding the genetic consequences of environmental toxicant exposure: Chernobyl as a model system. Environ Toxicol Chem 28:1982–1994CrossRefGoogle Scholar
  35. Milisav I, Poljsak B, Suput D (2012) Adaptive response, evidence of cross-resistance and its potential clinical use. Int J Mol Sci 13:10771–10806CrossRefGoogle Scholar
  36. Møller AP, Bonisoli-Alquati A, Rudolfsen G, Mousseau TA (2012) Elevated mortality among birds in Chernobyl as judged from skewed age and sex ratios. PLoS One 7:e35223ADSCrossRefGoogle Scholar
  37. Morgan WT (2003a) 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 159:581–596CrossRefGoogle Scholar
  38. Morgan WF (2003b) Non-targeted and delayed effects of exposure to ionizing radiation: I. Radiation-induced genomic instability and bystander effects in vitro. Radiat Res 159:567–580CrossRefGoogle Scholar
  39. Mothersill C, Seymour C (1997a) Lethal mutations and genomic instability. Int J Radiat Biol 77:751–758Google Scholar
  40. Mothersill C, Seymour C (1997b) Medium from irradiated human epithelial cells but not human fibroblasts reduces the clonogenic survival of unirradiated cells. Int J Radiat Biol 71:421–427CrossRefGoogle Scholar
  41. Mothersill C, Seymour CB (1998) Cell-cell contact during gamma irradiation is not required to induce a bystander effect in normal human keratinocytes: evidence for release during irradiation of a signal controlling survival into the medium. Radiat Res 149:256–262CrossRefGoogle Scholar
  42. Mothersill C, Seymour CB (2006) Radiation-induced bystander effects and the DNA paradigm: an “out of field” perspective. Mutat Res 597:5–10CrossRefGoogle Scholar
  43. Mothersill C, Seymour C (2009) Implications for environmental health of multiple stressors. J Radiol Prot 29:A21–A28CrossRefGoogle Scholar
  44. Mothersill C, Seymour C (2010) Eco-systems biology—from the gene to the stream. Mutat Res 687:63–66CrossRefGoogle Scholar
  45. Mothersill C, Seymour C (2011) Radiation-induced non-targeted effects of low doses—what, why and how? Health Phys 100:302CrossRefGoogle Scholar
  46. Mothersill C, Seymour C (2012) Changing paradigms in radiobiology. Mutat Res 750:85–95CrossRefGoogle Scholar
  47. Mothersill C, Harney J, Lyng F, Cottell D, Parsons K, Murphy DM, Seymour CB (1995) Primary explants of human uroepithelium show an unusual response to low-dose irradiation with cobalt-60 gamma rays. Radiat Res 142:181–187CrossRefGoogle Scholar
  48. Mothersill C, Stamato TD, Perez ML, Cummins R, Mooney R, Seymour CB (2000) Involvement of energy metabolism in the production of ‘bystander effects’ by radiation. Br J Cancer 82:1740–1746CrossRefGoogle Scholar
  49. Mothersill C, Lyng F, Seymour C, Maguire P, Lorimore S, Wright E (2005) Genetic factors influencing bystander signaling in murine bladder epithelium after low-dose irradiation in vivo. Radiat Res 163:391–399CrossRefGoogle Scholar
  50. Multhoff G, Radons J (2012) Radiation, inflammation, and immune responses in cancer. Front Oncol 2:(article 58)Google Scholar
  51. Nagasawa H, Little JB (1992) Induction of sister chromatid exchanges by extremely low doses of alpha-particles. Cancer Res 52:6394–6396Google Scholar
  52. Ozasa K, Shimizu Y, Sakata R, Sugiyama H, Grant EJ, Soda M, Kasagi F, Suyama A (2011) Risk of cancer and non-cancer diseases in the atomic bomb survivors. Radiat Prot Dosim 146:272–275CrossRefGoogle Scholar
  53. Pentreath RJ (2012) Radiation and protection of the environment: the work of Committee 5. Ann ICRP 41:45–56CrossRefGoogle Scholar
  54. Poon RC, Agnihotri N, Seymour C, Mothersill C (2007) Bystander effects of ionizing radiation can be modulated by signaling amines. Environ Res 105:200–211CrossRefGoogle Scholar
  55. Prise KM, Belyakov OV, Folkard M, Michael BD (1998) Studies of bystander effects in human fibroblasts using a charged particle microbeam. Int J Radiat Biol 74:793–798CrossRefGoogle Scholar
  56. Prise KM, Folkard M, Michael BD (2003) A review of the bystander effect and its implications for low dose exposure. Radiat Prot Dosim 104:347–355CrossRefGoogle Scholar
  57. Rigaud O (1999) The adaptive response to ionizing radiation: low dose effects unpredictable from high dose experiments. Hum Exp Toxicol 18:443–446CrossRefGoogle Scholar
  58. Rödel F, Frey B, Gaipl U, Keilholz L, Fournier C, Manda K, Schöllnberger H, Hildebrandt G, Rödel C (2012) Modulation of inflammatory immune reactions by low-dose ionizing radiation: molecular mechanisms and clinical application. Curr Med Chem 19:1741–1750CrossRefGoogle Scholar
  59. Rozhdestvenskiĭ LM (2011) The threshold for radiation stochastic effects: arguments “pro” and “contra”. Applied realization. Radiats Biol Radioecol 51:576–594Google Scholar
  60. Rubner Y, Wunderlich R, Rühle PF, Kulzer L, Werthmöller N, Frey B, Weiss EM, Keilholz L, Fietkau R, Gaipl US (2012) How does ionizing irradiation contribute to the induction of anti-tumor immunity? Front Oncol 2:(article 75)Google Scholar
  61. Ryan LA, Seymour CB, Mothersill CE (2009a) Investigation of non-linear adaptive responses and split dose recovery induced by ionizing radiation in three human epithelial derived cell lines. Dose Response 7:292–306CrossRefGoogle Scholar
  62. Ryan LA, Seymour CB, Joiner MC, Mothersill CE (2009b) Radiation-induced adaptive response is not seen in cell lines showing a bystander effect but is seen in lines showing HRS/IRR response. Int J Radiat Biol 85:87–95CrossRefGoogle Scholar
  63. Schaue D, Kachikwu EL, McBride WH (2012) Cytokines in radiobiological responses: a review. Radiat Res 178(6):505–523Google Scholar
  64. Schettino G, Folkard M, Prise KM, Vojnovic B, Held KD, Michael BD (2003) Low-dose studies of bystander cell killing with targeted soft X rays. Radiat Res 160:505–511CrossRefGoogle Scholar
  65. Schettino G, Folkard M, Michael BD, Prise KM (2005) Low-dose binary behavior of bystander cell killing after microbeam irradiation of a single cell with focused c(k) x rays. Radiat Res 163:332–336CrossRefGoogle Scholar
  66. Segner H (2011) Moving beyond a descriptive aquatic toxicology: the value of biological process and trait information. Aquat Toxicol 105:50–55CrossRefGoogle Scholar
  67. Selzer E, Hebar A (2012) Biological effect and tumor risk of diagnostic x-rays: the “war of the theories”. Radiologe 52:892–897CrossRefGoogle Scholar
  68. Seymour CB, Mothersill C (1997) Delayed expression of lethal mutations and genomic instability in the progeny of human epithelial cells that survived in a bystander-killing environment. Radiat Oncol Investig 5:106–110CrossRefGoogle Scholar
  69. Seymour CB, Mothersill C (2000) Relative contribution of bystander and targeted cell killing to the low-dose region of the radiation dose-response curve. Radiat Res 153:503–511CrossRefGoogle Scholar
  70. Seymour CB, Mothersill C, Alper T (1986) High yields of lethal mutations in somatic mammalian cells that survive ionizing radiation. Int J Radiat Biol Relat Stud Phys Chem Med 50:167–179CrossRefGoogle Scholar
  71. Seymour CB, Mothersill C, Mooney R, Moriarty M, Tipton KF (2003) Monoamine oxidase inhibitors l-deprenyl and clorgyline protect nonmalignant human cells from ionising radiation and chemotherapy toxicity. Br J Cancer 89:1979–1986CrossRefGoogle Scholar
  72. Shadley JD, Afzal V, Wolff S (1987) Characterization of the adaptive response to ionizing radiation induced by low doses of X rays to human lymphocytes. Radiat Res 111:511–517CrossRefGoogle Scholar
  73. Smith RW, Mothersill C, Hinton T, Seymour CB (2011) Exposure to low level chronic radiation leads to adaptation to a subsequent acute X-ray dose and communication of modified acute X-ray induced bystander signals in medaka (Japanese rice fish, Oryzias latipes). Int J Radiat Biol 87:1011–1022CrossRefGoogle Scholar
  74. Sorokina SS, Zaichkina SI, Rozanova OM, Aptikaeva GF, Akhmadieva AKh, Smirnova EN, Romanchenko SP, Vakhrusheva OA, Dyukina AR, Peleshko VN (2011) Delayed effects of chronic low-dose high linear energy transfer (LET) radiation on mice in vivo. Radiat Prot Dosim 143:305–310CrossRefGoogle Scholar
  75. Stewart FA (2012) Mechanisms and dose-response relationships for radiation-induced cardiovascular disease. Ann ICRP 41:72–79CrossRefGoogle Scholar
  76. Tanner RJ, Eakins JS, Jansen JT, Harrison JD (2012) Doses and risks from uranium are not increased significantly by interactions with natural background photon radiation. Radiat Prot Dosim 151:323–343CrossRefGoogle Scholar
  77. Vanhoudt N, Vandenhove H, Horemans N, Wannijn J, Van Hees M, Vangronsveld J, Cuypers A (2010) The combined effect of uranium and gamma radiation on biological responses and oxidative stress induced in Arabidopsis thaliana. J Environ Radioact 101:923–930CrossRefGoogle Scholar
  78. Vanhoudt N, Vandenhove H, Real A, Bradshaw C, Stark K (2012) A review of multiple stressor studies that include ionising radiation. Environ Pollut 168:177–192CrossRefGoogle Scholar
  79. Wright EG, Coates PJ (2006) Untargeted effects of ionizing radiation: implications for radiation pathology. Mutat Res 597:119–132CrossRefGoogle Scholar
  80. Wrixon AD (2008) New ICRP recommendations. J Radiol Prot 28:161–168CrossRefGoogle Scholar
  81. Zhou H, Randers-Pehrson G, Waldren CA, Vannais D, Hall EJ, Hei TK (2000) Induction of a bystander mutagenic effect of alpha particles in mammalian cells. Proc Natl Acad Sci USA 97:2099–2104ADSCrossRefGoogle Scholar
  82. Zyuzikov NA, Coates PJ, Parry JM, Lorimore SA, Wright EG (2011) Lack of nontargeted effects in murine bone marrow after low-dose in vivo X irradiation. Radiat Res 175:322–327CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Department of Medical Physics and Applied Radiation SciencesMcMaster UniversityHamiltonCanada

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