Skip to main content
SpringerLink
Log in
Book cover

Therapeutic Nuclear Medicine pp 789–805Cite as

Hormesis by Low Dose Radiation Effects: Low-Dose Cancer Risk Modeling Must Recognize Up-Regulation of Protection

Part of the Medical Radiology book series (Med Radiol Radiat Oncol)

Abstract

Ionizing radiation primarily perturbs the basic molecular level proportional to dose, with potential damage propagation to higher levels: cells, tissues, organs, and whole body. There are three types of defenses against damage propagation. These operate deterministically and below a certain impact threshold there is no propagation. Physical static defenses precede metabolic-dynamic defenses acting immediately: scavenging of toxins;—molecular repair, especially of DNA;—removal of damaged cells either by apoptosis, necrosis, phagocytosis, cell differentiation-senescence, or by immune responses,—followed by replacement of lost elements. Another metabolic-dynamic defense arises delayed by up-regulating immediately operating defense mechanisms. Some of these adaptive protections may last beyond a year and all create temporary protection against renewed potentially toxic impacts also from nonradiogenic endogenous sources. Adaptive protections have a maximum after single tissue absorbed doses around 100–200 mSv and disappear with higher doses. Low dose-rates initiate maximum protection likely at lower cell doses delivered repetitively at certain time intervals. Adaptive protection preventing only about 2–3 % of endogenous lifetime cancer risk would fully balance a calculated-induced cancer risk at about 100 mSv, in agreement with epidemiological data and concordant with an hormetic effect. Low-dose-risk modeling must recognize up-regulation of protection.

Keywords

  • Low-dose cancer risk
  • Adaptive protections
  • Hormesis

This work represents the opinion of its authors. It should not be read as representing the position of the NIH, DHHS, nor the US Government.

This chapter corresponds to a paper published by Dose-Response in June 2010 and is given here by permission from the journal Dose-Response.

This is a preview of subscription content, access via your institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   299.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  • Azzam EI, de Toledo SM, Raaphorst GP, Mitchel REJ (1996) Low-dose ionizing radiation decreases the frequency of neoplastic transformation to a level below the spontaneous rate in C3H 10T1/2 cells. Radiat Res 146:369–373

    CrossRef  CAS  PubMed  Google Scholar 

  • Barcellos-Hoff MH, Brooks AL (2001) Extracellular signaling through the microenvironment: a hypothesis relating carcinogenesis; bystander effects, and genomic instability. Radiat Res 156:618–627

    CrossRef  CAS  PubMed  Google Scholar 

  • Bond VP, Fiedner TM, Archambeau JO (1966) Mammalian Radiation Lethality: a Disturbance in Cellular Kinetics. Academic Press, New York

    Google Scholar 

  • Bond VP, Benary V, Sondhaus CA, Feinendegen LE (1995) The meaning of linear dose-response relations, made evident by use of absorbed dose to the cell. Health Phys 68:786–792

    CrossRef  CAS  PubMed  Google Scholar 

  • Brenner DJ, Hall EJ (2007) Computed tomography–an increasing source of radiation exposure. N Engl J Med 357:2277–2284

    CrossRef  CAS  PubMed  Google Scholar 

  • Calabrese EJ, Baldwin LA (2003) Toxicology rethinks its central belief. Nature 421:691–692

    CrossRef  CAS  PubMed  Google Scholar 

  • Cardis E et al (2007) The 15-country collaborative study of cancer risk among radiation workers in the nuclear workers in the nuclear industry: estimates of radiation-related cancer risks. Radiat Res 167:396–416

    CrossRef  CAS  PubMed  Google Scholar 

  • Chandra J, Samali A, Orrenius S (2000) Triggering and modulation of apoptosis by oxidative stress. Free Radic Biol Med 29:323–333

    CrossRef  CAS  PubMed  Google Scholar 

  • Day TK, Zeng G, Hooker AM, Bhat M, Scott BR, Turner DR, Sykes PJ (2006) Extremely low priming doses of X radiation induce an adaptive response for chromosomal inversions in pKZ1 mouse prostate. Radiat Res 166:757–766

    CrossRef  CAS  PubMed  Google Scholar 

  • Dziegielewski J, Baulch JE, Goetz W, Coleman MC, Spitz DR, Murley JS, Grdina DJ, Morgan WF (2008) WR-1065, the active metabolite of amifostine, mitigates radiation-induced delayed genomic instability. Free Radic Biol Med 45:1674–1681

    CrossRef  CAS  PubMed Central  PubMed  Google Scholar 

  • Elmore E, Lao X-Y, Kapadia R, Redpath JL (2009) Threshold-type dose response for induction of neoplastic transformation by 1 GeV/nucleon iron ions. Radiat Res 171:764–770

    CrossRef  CAS  PubMed  Google Scholar 

  • Feinendegen LE (2002) Reactive oxygen species in cell responses to toxic agents. Hum Exp Toxicol 21:85–90

    CrossRef  CAS  PubMed  Google Scholar 

  • Feinendegen LE (2005) Evidence for beneficial low level radiation effects and radiation hormesis. Brit J Radiol 78:3–7

    CrossRef  CAS  PubMed  Google Scholar 

  • Feinendegen LE, Neumann RD (2005) Physics must join with biology in better assessing risk from low-dose irradiation. Rad Prot Dosim 117:346–356

    CrossRef  CAS  Google Scholar 

  • Feinendegen LE, Muehlensiepen H, Lindberg C, Marx J, Porschen W, Booz J (1984) Acute and temporary inhibition of thymidine kinase in mouse bone marrow cells after low-dose exposure. Intern J Radiat Biol 45:205–215

    CrossRef  CAS  Google Scholar 

  • Feinendegen LE, Loken MK, Booz J, Muehlensiepen H, Sondhaus CA, Bond VP (1995) Cellular mechanisms of protection and repair induced by radiation exposure and their consequences for cell system responses. Stem Cells 13(1):7–20

    PubMed  Google Scholar 

  • Feinendegen LE, Bond VP, Sondhaus CA, Muehlensiepen H (1996) Radiation effects induced by low doses in complex tissue and their relation to cellular adaptive responses. Mutat Res 358:199–205

    CrossRef  PubMed  Google Scholar 

  • Feinendegen LE, Bond VP, Sondhaus CA, Altman KI (1999) Cellular signal adaptation with damage control at low doses versus the predominance of DNA damage at high doses. C.R Acad Sci Paris, Life Sciences 322:245–251

    CAS  Google Scholar 

  • Feinendegen LE, Neumann RD (eds) (2000) Cellular responses to low doses of ionizing radiation. Workshop of the US department of energy (DOE), Washington, and the national institutes of health (NIH), Bethesda, held on 27–30 April 1999 at the Mary Woodward Lasker Center, Cloister, NIH DOE Report Publication SC-047

    Google Scholar 

  • Feinendegen LE, Bond VP, and Sondhaus CA (2000) The dual response to low-dose irradiation: induction versus prevention of DNA damage. In: Yamada T, Mothersill C, Michael BD, Potten CS (eds), Biological effects of low dose radiation, Excerpta Medica, International Congress Serie 1211. Elsevier, Amsterdam pp 3–17

    Google Scholar 

  • Feinendegen LE, Pollycove M, Sondhaus CA (2004) Responses to low doses of ionizing radiation in biological systems. Nonlinearity in Biol Toxicol Med 2:143–171

    CrossRef  CAS  Google Scholar 

  • Feinendegen LE, Pollycove M, Neumann RD (2007a) Whole body responses to low-level radiation exposure: new concepts in mammalian radiobiology. Exp Hematol 35:37–46

    CrossRef  CAS  PubMed  Google Scholar 

  • Feinendegen LE, Paretzke HG, Neumann RD (2007b) Damage propagation in complex biological systems following exposure to low doses of ionizing radiation. AFP: Int J 1:336–354

    CrossRef  Google Scholar 

  • Feinendegen LE, Paretzke HG, Neumann RD (2008) Response to Comments by Dr. de Saint Georges: damage propagation in complex biological systems following exposure to low doses of ionizing radiation. AFP: Int J 2:206–210

    CrossRef  Google Scholar 

  • Feinendegen LE, Brooks AL, Morgan WF (2011) Biological consequences and health risks of low-level exposure to ionizing radiation: commentary on the workshop. Health Phys 100:247–259

    CrossRef  CAS  PubMed  Google Scholar 

  • Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of aging. Nature 408:239–247

    CrossRef  CAS  PubMed  Google Scholar 

  • Fliedner TN, Dörr H, Meineke V (2005) Multi-organ involvement as a pathogenic principle of the radiation syndromes: a study involving 110 case histories documented in SEARCH and classified as the bases of haematopoetic indicators of effect. Brit J Radiol Suppl 27:1–8

    CrossRef  CAS  Google Scholar 

  • Franco N, Lamartine J, Frouin V, Le Minter P, Petat C, Leplat JJ, Libert F, Gidrol X, Martin MT (2005) Low-dose exposure to gamma rays induces specific gene regulations in normal human keratinocytes. Radiat Res 163:623–635

    CrossRef  CAS  PubMed  Google Scholar 

  • Fujita K, Ohtomi M, Ohyama H, and Yamada T (1998) Biphasic induction of apoptosis in the spleen after fractionated exposure of mice to very low doses of ionizing g radiation. In: Yamada T, Hashimoto Y (eds), Apoptosis, its role and mechanism, Business Center for Academic Societies Japan, Tokyo, pp 201–218

    Google Scholar 

  • Guyton AC, Hall JE (2005) Textbook of medical physiology, 11th edn. WB Saunders Company, Philadelphia

    Google Scholar 

  • Hall EJ, Giaccia AJ (2005) Radiobiology for the Radiologist, 6th edn. Lippincott Williams & Wilkins, New York

    Google Scholar 

  • Harder D (2008) Ionisierende Strahlung and die Dosiabhängigkeit ihrer Wirkung. Nova Acta Leopoldina NF 96(355):21–44

    CAS  Google Scholar 

  • Heidenreich WF, Hoogenweem R (2001) Limits of applicability for the deterministic approximation of the two-step cloncal expansion model. Risk Anal 21:103–105

    CrossRef  CAS  PubMed  Google Scholar 

  • Heidenreich WF, Paretzke HG, Jacob P (1997) No evidence for increased tumour rates below 200 mSv in atomic bomb survivors. Radiat Environ Biophys 36(3):205–207

    CrossRef  CAS  PubMed  Google Scholar 

  • Hohn-el-Karim K, Muehlensiepen H, Altman KI, Feinendegen LE (1990) Modification of effects of radiation on thymidine kinase. Intern J Radiat Biol 58:97–110

    CrossRef  CAS  Google Scholar 

  • ICRP (International Commission on Radiation Protection) (1977) Recommendations of the international commission on radiological protection, ICRP Publication 26, Annals of the ICRP 1 No. 3

    Google Scholar 

  • ICRU (International Commission on Radiation Units and Measurements) (1983) Microdosimetry. Report 36, ICRU, Bethesda

    Google Scholar 

  • ICRU (International Commission on Radiation Units and Measurements) (2005) Patient dosimetry of X-rays used in medical imaging, Report 74, J ICRU; Oxford J, Oxford University Press, Oxford

    Google Scholar 

  • ICRU (International Commission on Radiation Units and Measurements) (2011) Quantification and reporting of low-dose and other heterogeneous exposures. Report 86, J ICRU; Oxford University Press, Oxford

    Google Scholar 

  • ICRU (Internationalö Comnission on Radiaiton Units and Measurements) (1998) Fundamental quanititis and units for ionizting radiaiton, report 60. ICRU, Bethesda

    Google Scholar 

  • ICRU (International Commission on Radiation Units and Measurements) (2002) Acsorbed dose specification in nuclerar medicine, Report 67, J thw ICRU; Oxford J, Oxford University Press, Oxford

    Google Scholar 

  • Ishizaki K, Hayashi Y, Nakamura H, Yasui Y, Komatsu K, Tachibana A (2004) No induction of p53 phosphorylation and few focus formation of phosphorylated H2AX suggest efficient repair of DNA damage during chronic low-dose-rate irradiation in human cells. J Radiat Res 45:521–525

    CAS  PubMed  Google Scholar 

  • James SJ, Makinodan T (1990) T-cell potentiation by low dose ionizing radiation: possible mechanisms. Health Phys 59:29–34

    CrossRef  PubMed  Google Scholar 

  • Kadhim MA, Hill MA, Moore SR (2006) Genomic instability and the role of radiation quality. Radiat Prot Dosimetry 122:221–227

    CrossRef  CAS  PubMed  Google Scholar 

  • Kondo S (1988) Altruistic cell suicide in relation to radiation hormesis. Intern J Radiat Biol 53:95–102

    CrossRef  CAS  Google Scholar 

  • Leonard BE (2007) Adaptive response and human benefit: Part I—a microdosimetric dose dependent model. Intern J Radiat Biol 83:115–131

    CrossRef  CAS  Google Scholar 

  • Liu SZ, Zhang YC, Mu Y, Su X, Liu JX (1996) Thymocyte apoptosis in response to low-dose radiation. Mutat Res 358:185–191

    CrossRef  PubMed  Google Scholar 

  • Mitchel REJ, Jackson JS, Morrison DP, Carlisle SM (2003) Low doses of radiation increase the latency of spontaneous lymphomas and spinal osteosarcomas in cancer prone, radiation sensitive Trp53 heterozygous mice. Radiat Res 159:320–327

    CrossRef  CAS  PubMed  Google Scholar 

  • Mitchel RE, Burchart P, Wyatt H (2008) A lower dose threshold for the in vivo protective adaptive response to radiation. Tumorigenesis in chronically exposed normal and Trp53 heterozygous C57BL/6 mice. Radiat Res 170:765–775

    CrossRef  CAS  PubMed  Google Scholar 

  • Morgan WF, Sowa MB (2009) Non-targeted effects of ionizing radiation: Implications for risk assessment and the radiation dose response profile. Health Phys 97:426–432

    CrossRef  CAS  PubMed  Google Scholar 

  • Mothersill C, Seymour CB (2006) Radiation-induced bystander effects and the DNA paradigm: an “out of field” perspective. Mutat Res 59:5–10

    CrossRef  Google Scholar 

  • Mullenders L, Atkinson M, Paretzke H, Sabatier L, Bouffler S (2009) Assessing cancer risk of low-dose radiation. Nat Rev/Cancer 9:596–604

    CrossRef  CAS  Google Scholar 

  • Nair RR, Rajan B, Akiba S, Jayalekshmi P, Nair MK, Gangadharan P, Koga T, Morishima H, Nakamura S, Sugahara T (2009) Background radiation and cancer incidence in Kerala, India-Karanagappally cohort study. Health Phys 96:55–66

    CrossRef  CAS  PubMed  Google Scholar 

  • National Research Council, Committee to Assess Health Risks from Exposure to Low Levels of Ionizing Radiation (2006) Health risks from low levels of ionizing radiation: BEIR VII, Phase 2. The National Academies Press, Washington

    Google Scholar 

  • Neumaier T, Swenson J, Pham C, Polyzos A, Lo AT, Yang PA, Dyball J, Asaithamby A, Chen DJ, Bissell MJ, Thalhammer S, Costes SV (2012) Evidence for formation of DNA repair centers and dose-response nonlinearity in human cells. Proc Nat Acad Sci US 109:443–448

    CrossRef  Google Scholar 

  • Nikjoo H, O’Neill P, Terrissol M, Goodhead DT (1999) Quantitative modelling of DNA damage using Monte-Carlo track structure method. Radiat Envrion Biophys 38:31–38

    CrossRef  CAS  Google Scholar 

  • Olivieri G, Bodycote J, Wolff S (1984) Adaptive response of human lymphocytes to low concentration of radioactive thymidine. Science 223:594–597

    CrossRef  CAS  PubMed  Google Scholar 

  • Pollycove M, Feinendegen LE (2001) Biologic response to low doses of ionizing radiation: detriment versus hormesis. Part 2: dose responses of organisms. J Nucl Med 42:26N–32N

    CAS  PubMed  Google Scholar 

  • Pollycove M, Feinendegen LE (2003) Radiation-induced versus endogenous DNA damage: possible effect of inducible protective responses in mitigating endogenous damage. Hum Exp Toxicol 22:290–306

    CrossRef  CAS  PubMed  Google Scholar 

  • Preston DL, Pierce DA, Shimizu Y, Cullings HM, Fujita S, Funamoto S, Kodama K (2004) Effect of recent changes in atomic bomb survivor dosimetry on cancer mortality risk estimates. Radiat Res 162:377–389

    CrossRef  CAS  PubMed  Google Scholar 

  • Preston DL, Ron E, Tokuoka S, Funamoto S, Nishi N, Soda M, Mabuchi K, Kodama K (2007) Solid cancer incidence in atomic bomb survivors: 1958–1998. Radiat Res 168:1–64

    CrossRef  CAS  PubMed  Google Scholar 

  • Rothkamm K, Löbrich M (2003) Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses’. Proc Natl Acad Sci US 100:5057–5062

    CrossRef  CAS  Google Scholar 

  • Schöllnberger H, Stewart RD, Mitchel REJ (2005) Low-LET-induced radioprotective mechanisms within a stochastic two-stage cancer model. Dose-Response 3:508–518

    CrossRef  PubMed Central  Google Scholar 

  • Scott BR (2004) A biological-based model that.links genomic instability; bystander effects, and adaptive response. Mutat Res 568:129–143

    CrossRef  CAS  PubMed  Google Scholar 

  • Sedelnikova OA, Horikawa I, Zimonjic DB, Popescu NC, Bonner WM, Barrett JC (2004) Senescing human cells and ageing mice accumulate DNA lesions with unrepairable double-strand breaks. Nature Cell Biol 6:168–170

    CrossRef  CAS  PubMed  Google Scholar 

  • Sen K, Sies H, Baeurle P (eds) (2000) Redox regulation of gene expression. Academic Press, San Diego

    Google Scholar 

  • Tanooka H (2001) Threshold dose-response in radiation carcinogenesis: an approach from chronic beta-irradiation experiments and a review of non-tumour doses. Int J Radiat Biol 77:541–551

    CrossRef  CAS  PubMed  Google Scholar 

  • Tanooka H (2011) Meta-analysis of non-tumour doses for radiation-induced cancer on the basis of dose-rate. Int J Radiat Biol 87:645–652

    CrossRef  CAS  PubMed Central  PubMed  Google Scholar 

  • Tubiana M, Aurengo A, Averbeck D, et al. (2005). Dose-effect relationships and the estimation of the carcinogenic effects of low doses of ionizing radiation. Academy of Medicine (Paris) and Academy of Science (Paris) Joint Report No. 2

    Google Scholar 

  • Tubiana M, Feinendegen LE, Yang CJM, Kaminski JM (2009) The linear no-threshold relationship is inconsistent with radiation biologic and experimental data. Radiology 251:13–22

    CrossRef  PubMed Central  PubMed  Google Scholar 

  • Vilenchik MM, Knudson AG (2000) Inverse radiation dose-rate effects on somatic and germ-line mutations and DNA damage rates. Proc Natl Acad Sci US 97:5381–5386

    CrossRef  CAS  Google Scholar 

  • Wolff S, Afzal V, Wienke JK, Olivieri G, Michaeli A (1988) Human lymphocytes exposed to low doses of ionizing radiations become refractory to high doses of radiation as well as to chemical mutagens that induce double-strand breaks in DNA. Intern J Radiat Biol 53:39–49

    CrossRef  CAS  Google Scholar 

  • Zamboglou N, Porschen W, Muehlensiepen H, Booz J, Feinendegen LE (1981) Low dose effect of ionizing radiation on incorporation of iodo-deoxyuridine into bone marrow cells. Int J Radiat Biol 39:83–93

    CrossRef  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Heinrich-Heine-University, Düsseldorf, Germany

    Ludwig E. Feinendegen

  2. Brookhaven National Laboratory, Upton, NY, USA

    Ludwig E. Feinendegen

  3. School of Medicine, University of California San Francisco, San Francisco, CA, USA

    Myron Pollycove

  4. Radiology and Imaging Sciences, Clinical Center, The National Institutes of Health, Bethesda, MD, USA

    Ronald D. Neumann

Authors
  1. Ludwig E. Feinendegen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Myron Pollycove
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ronald D. Neumann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ludwig E. Feinendegen .

Editor information

Editors and Affiliations

  1. THERANOSTICS Center for Molecular, Radiotherapy and Molecular Imaging, ENETS Center of Excellence, Bad Berka, Germany

    Richard P. Baum

Copyright information

© 2012 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Feinendegen, L.E., Pollycove, M., Neumann, R.D. (2012). Hormesis by Low Dose Radiation Effects: Low-Dose Cancer Risk Modeling Must Recognize Up-Regulation of Protection. In: Baum, R. (eds) Therapeutic Nuclear Medicine. Medical Radiology(). Springer, Berlin, Heidelberg. https://doi.org/10.1007/174_2012_686

Download citation

  • DOI: https://doi.org/10.1007/174_2012_686

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-36718-5

  • Online ISBN: 978-3-540-36719-2

  • eBook Packages: MedicineMedicine (R0)

search

Navigation