Skip to main content

Advertisement

SpringerLink
Log in

Individual response of humans to ionising radiation: governing factors and importance for radiological protection

  • Review
  • Published:
Radiation and Environmental Biophysics Aims and scope Submit manuscript

Abstract

Tissue reactions and stochastic effects after exposure to ionising radiation are variable between individuals but the factors and mechanisms governing individual responses are not well understood. Individual responses can be measured at different levels of biological organization and using different endpoints following varying doses of radiation, including: cancers, non-cancer diseases and mortality in the whole organism; normal tissue reactions after exposures; and, cellular endpoints such as chromosomal damage and molecular alterations. There is no doubt that many factors influence the responses of people to radiation to different degrees. In addition to the obvious general factors of radiation quality, dose, dose rate and the tissue (sub)volume irradiated, recognized and potential determining factors include age, sex, life style (e.g., smoking, diet, possibly body mass index), environmental factors, genetics and epigenetics, stochastic distribution of cellular events, and systemic comorbidities such as diabetes or viral infections. Genetic factors are commonly thought to be a substantial contributor to individual response to radiation. Apart from a small number of rare monogenic diseases such as ataxia telangiectasia, the inheritance of an abnormally responsive phenotype among a population of healthy individuals does not follow a classical Mendelian inheritance pattern. Rather it is considered to be a multi-factorial, complex trait.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Adams J (2000) Risk. Routledge, Taylor and Francis Group, London

    Google Scholar 

  • AGIR (2013) Human Radiosensitivity. Report of the Independent Advisory Group on Ionising Radiation. Doc HPA, RCE-21. Advisory Group on Ionising Radiation, Chilton

  • Ariyoshi K, Takabatake T, Shinagawa M, Kadono K, Daino K, Imaoka T, Kakinuma S, NishimuraM SY (2014) Age dependence of hematopoietic progenitor survival and chemokine family gene induction after gamma irradiation in bone marrow tissue in C3H/He mice. Radiat Res 181(3):302–313. https://doi.org/10.1667/RR13466

    Article  ADS  Google Scholar 

  • Badie C, Dziwura S, Raffy C et al (2008) Aberrant CDKN1A transcriptional response associates with abnormal sensitivity to radiation treatment. Br J Cancer 98(11):1845–1851

    Google Scholar 

  • Ban S, Konomi C, Iwakawa M, Yamada S, Ohno T, Tsuji H, Noda S, Matui Y, Harada Y, Cologne JB, Imai T (2004) Radiosensitivity of peripheral blood lymphocytes obtained from patients with cancers of the breast, head and neck or cervix as determined with a micronucleus assay. JRR 45:535–541

    Google Scholar 

  • Ban S, Ishikawa K, Kawai S, Koyama-Saegusa K, Ishikawa A, Shimada Y, Inazawa J, Imai T (2005) Potential in a single cancer cell to produce heterogeneous morphology, radiosensitivity and gene expression. JRR 46:43–50

    Google Scholar 

  • Barnett GC, Thompson D, Fachal L, Kerns S, Talbot C, Elliott RM, Dorling L, Coles CE, Dearnaley DP, Rosenstein BS, Vega A, Symonds P, Yarnold J, Baynes C, Michailidou K, Dennis J, Tyrer JP, Wilkinson JS, Gómez-Caamaño A, Tanteles GA, Platte R, Mayes R, Conroy D, Maranian M, Luccarini C, Gulliford SL, Sydes MR, Hall E, Haviland J, Misra V, Titley J, Bentzen SM, Pharoah PD, Burnet NG, Dunning AM, West CM (2014) A genome wide association study (GWAS) providing evidence of an association between common genetic variants and late radiotherapy toxicity. Radiother Oncol 111(2):178–185

    Google Scholar 

  • Barnett GC, West CM, Dunning AM, Elliott RM, Coles CE, Pharoah PD, Burnet NG (2009) Normal tissue reactions to radiotherapy: towards tailoring treatment dose by genotype. Nat Rev Cancer 9:134–142

    Google Scholar 

  • Bentzen SM, Constine LS, Deasy JO et al (2010) Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC): an introduction to the scientific issues. Int J Radiat Oncol Biol Phys 76(3 Suppl):S3–9

    Google Scholar 

  • Bergonie J, Tribondeau L (1959) Interpretation of some results of radiotherapy and an attempt at determining a logical technique of treatment. Radiat Res 11:587–588

    ADS  Google Scholar 

  • Bernier MO, Baysson H, Pearce MS, Moissonnier M, Cardis E, Hauptmann M, Struelens L, Dabin J, Johansen C, Journy N, Laurier D, Blettner M, Le Cornet L, Pokora R, Gradowska P, Meulepas JM, Kjaerheim K, Istad T, Olerud H, Sovik A, Bosch de Basea M, Thierry-Chef I, Kaijser M, Nordenskjöld A, Berrington de Gonzalez A, Harbron RW, Kesminiene A (2018) Cohort profile: the EPI-CT study: a European pooled epidemiological study to quantify the risk of radiation-induced cancer from paediatric CT. Int J Epidemiol. https://doi.org/10.1093/ije/dyy231

    Article  Google Scholar 

  • Berthel E, Foray N, Ferlazzo ML (2019) The nucleoshuttling of the atm protein: a unified model to describe the individual response to high and low-dose of radiation? Cancers 11:905. https://doi.org/10.3390/cancers11070905

    Article  Google Scholar 

  • Boice JD Jr, Miller RW (2009) Childhood and adult cancer after intrauterine exposure to ionizing radiation. Teratology 59:227–323

    Google Scholar 

  • Bourguignon MH, Gisone PA, Perez MR, Michelin S, Dubner D, Giorgio M, Carosella ED (2005) Genetic and epigenetic features in radiation sensitivity. Part II: implications for clinical practice and radiation protection. Eur J Nucl Med Mol I 32:351–368

    Google Scholar 

  • Bremer M, Klöpper K, Yamini P, Bendix-Waltes R, Dörk T, Karstens JH (2003) Clinical radiosensitivity in breast cancer patients carrying pathogenic ATM gene mutations: no observation of increased radiation-induced acute or late effects. Radiother Oncol 69:155–160

    Google Scholar 

  • Brennan RM, Miles JJ, Silins SL, Bell MJ, Burrows JM (2007) Burrows SR (2007) Predictable alphabeta T-cell receptor selection toward an HLA-B*3501-restricted human cytomegalovirus epitope. J Virol 81:7269–7273

    Google Scholar 

  • Brennan RM, Petersen J, Neller MA, Miles JJ, Burrows JM, Smith C, McCluskey J, Khanna R, Rossjohn J, Burrows SR (2012) The impact of a large and frequent deletion in the human TCR β locus on antiviral immunity. J Immunol 188:2742–2748

    Google Scholar 

  • Brenner AV, Preston DL, Sakata R, Sugiyama H, de Gonzalez AB, French B, Utada M, Cahoon EK, Sadakane A, Ozasa K, Grant EJ, Mabuchi K (2018) Incidence of breast cancer in the life span study of atomic bomb survivors: 1958–2009. Radiat Res 190(4):433–444. https://doi.org/10.1667/RR15015.1

    Article  ADS  Google Scholar 

  • Britanova OV, Putintseva EV, Shugay M, Merzlyak EM, Turchaninova MA, Staroverov DB, Bolotin DA, Lukyanov S, Bogdanova EA, Mamedov IZ, Lebedev YB, Chudakov DM (2014) Age-related decrease in TCR repertoire diversity measured with deep and normalized sequence profiling. J Immunol 192:2689–2698

    Google Scholar 

  • Britel M, Bourguignon M, Foray N (2018) The use of the term ‘radiosensitivity’ through history of radiation: from clarity to confusion. Int J Radiat Biol 94:1–31

    Google Scholar 

  • Brooks JD, Boice JD, Jr., Stovall M, Reiner AS, Bernstein L, John EM, Lynch CF, Mellemkjaer L, Knight JA, Thomas DC, Haile RW, Smith SA, Capanu M, Bernstein JL, Shore RE, Group WC (2012) Reproductive status at first diagnosis influences risk of radiation-induced second primary contralateral breast cancer in the WECARE study. Int J Radiat Oncol Biol Phys 84(4):917–924. https://doi.org/10.1016/j.ijrobp.2012.01.047

    Article  Google Scholar 

  • Bruheim K, Guren MG, Skovlund E, Hjermstad MJ, Dahl O, Frykholm G, Carlsen E, Tveit K (2010) Late side effects and quality of life after radiotherapy for rectal cancer. Int J Radiat Oncol Biology Phys 76:1005–1011

    Google Scholar 

  • Burga A, Lehner B (2012) Beyond genotype to phenotype: why the phenotype of an individual cannot always be predicted from their genome sequence and the environment that they experience. FEBS J 279:3765–3775

    Google Scholar 

  • Castiglioni F, Terenziani M, Carcangiu ML, Miliano R, Aiello P, Bertola L, Triulzi T, Gasparini P, Camerini T, Sozzi G, Fossati-Bellani F, Menard S, Tagliabue E (2007) Radiation effects on development of HER2-positive breast carcinomas. Clin Cancer Res 13(1):46–51. https://doi.org/10.1158/1078-0432.CCR-06-1490

    Article  Google Scholar 

  • Civelek M, Lusis AJ (2014) Systems genetics approaches to understand complex traits. Nat Rev Genet 15:34–48

    Google Scholar 

  • Cooke R, Jones ME, Cunningham D, Falk SJ, Gilson D, Hancock BW, Harris SJ, Horwich A, Hoskin PJ, Illidge T, Linch DC, Lister TA, Lucraft HH, Radford JA, Stevens AM, Syndikus I, Williams MV, England and Wales Hodgkin Lymphoma Follow-up Group, Swerdlow AJ (2013) Breast cancer risk following Hodgkin lymphoma radiotherapy in relation to menstrual and reproductive factors. Br J Cancer 108(11):2399–2406. https://doi.org/10.1038/bjc.2013.219

    Article  Google Scholar 

  • Cosset JM, Hetnel M, Chargari C (2018) Second cancers after radiotherapy: update and recommendations. Radioprotection 53(2):101–105

    Google Scholar 

  • Cucinotta FA, Durante M (2006) Cancer risk from exposure to galactic cosmic rays: implications for space exploration by human beings. Lancet Oncol 7:431–435

    Google Scholar 

  • Cucinotta F (2010) Radiation Risk acceptability and limitations. https://three.jsc.nasa.gov/articles/AstronautRadLimitsFC.pdf. Accessed 21 Dec 2010

  • Cullings HM, Grant EJ, Egbert SD, Watanabe T, Oda T, Nakamura F et al (2017) DS02R1: improvements to atomic bomb survivors' input data and implementation of dosimetry system 2002 (DS02) and resulting changes in estimated doses. Health Phys 112(1):56–97. https://doi.org/10.1097/HP.0000000000000598

    Article  Google Scholar 

  • Czene K, Lichtenstein P, Hemminki K (2002) Environmental and heritable causes of cancer among 9.6 million individuals in the Swedish Family-Cancer Database. Int J Cancer 99:260–266

    Google Scholar 

  • Dagoglu N, Karaman S, Caglar HB, Oral EN (2019) Abscopal effect of radiotherapy in the immunotherapy era: systematic review of reported cases. Cureus 11(2):e4103. https://doi.org/10.7759/cureus.4103

    Article  Google Scholar 

  • Deschavanne PJ, Fertil B (1996) A review of human cell radiosensitivity in vitro. Int J Radiat Oncol Biol Phys 34(1):251–266

    Google Scholar 

  • Di Majo V, Coppola M, Rebessi S, Covelli V (1990) Age-related susceptibility of mouse liver to induction of tumors by neutrons. Radiat Res 124(2):227–234

    ADS  Google Scholar 

  • Doll R, Wakeford R (1997) Risk of childhood cancer from fetal irradiation. Br J Radiol 70:130–139

    Google Scholar 

  • Dores GM, Anderson WF, Beane Freeman LE, Fraumeni JF Jr, Curtis RE (2010) Risk of breast cancer according to clinicopathologic features among long-term survivors of Hodgkin's lymphoma treated with radiotherapy. Br J Cancer 103(7):1081–1084. https://doi.org/10.1038/sj.bjc.6605877

    Article  Google Scholar 

  • Egawa H, Furukawa K, Preston D, Funamoto S, Yonehara S, Matsuo T, Tokuoka S, Suyama A, Ozasa K, Kodama K, Mabuchi K (2012) Radiation and smoking effects on lung cancer incidence by histological types among atomic bomb survivors. Radiat Res 178(3):191–201

    ADS  Google Scholar 

  • Emami B, Lyman J, Brown A et al (1991) Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 21(1):109–122

    Google Scholar 

  • Fachal L, Gómez-Caamaño A, Barnett GC, Peleteiro P, Carballo AM, Calvo-Crespo P, Kerns SL, Sánchez-García M, Lobato-Busto R, Dorling L, Elliott RM, Dearnaley DP, Sydes MR, Hall E, Burnet NG, Carracedo Á, Rosenstein BS, West CM, Dunning AM, Vega A (2014) A three-stage genome-wide association study identifies a susceptibility locus for late radiotherapy toxicity at 2q24.1. Nat Genet 46(8):891–894

    Google Scholar 

  • Ferlazzo ML, Bourguignon M, Foray N (2017) Functional assays for individual radiosensitivity: a critical review. Radiat Oncol 27:310–315

    Google Scholar 

  • Flockerzi E, Schanz S, Rübe CE (2014) Even low doses of radiation lead to DNA damage accumulation in lung tissue according to the genetically-defined DNA repair capacity. Radiother Oncol 111(2):212–218

    Google Scholar 

  • Foray N, Colin C, Bourguignon M (2012) 100 years of individual radiosensitivity: how we have forgotten the evidence. Radiology 226(3):627–631

    Google Scholar 

  • Foray N, Bourguignon M, Hamada N (2016) Individual response to ionizing radiation. Mutat Res 770:369–386

    Google Scholar 

  • Fujiwara S, Carter RL, Akiyama M, Akahoshi M, Kodama K, Shimaoka K, Yamakido M (1994) Autoantibodies and immunoglobulins among atomic bomb survivors. Radiat Res 137(1):89–95

    ADS  Google Scholar 

  • Fukahori M, Matsufuji N, Himukai T, Kanematsu N, Mizuno H, Fukumura A et al (2016) Estimation of late rectal normal tissue complication probability parameters in carbon ion therapy for prostate cancer. Radiother Oncol 118:136–140

    Google Scholar 

  • Funatogawa I, Funatogawa T, Yano E (2013) Trends in smoking and lung cancer mortality in Japan, by birth cohort, 1949–2010. Bull World Health Organ 91:332–340

    Google Scholar 

  • Furukawa K, Preston D, Lönn S, Funamoto S, Yonehara S, Matsuo T, Egawa H, Tokuoka S, Ozasa K, Kasagi F, Kodama K, Mabuchi K (2010) Radiation and smoking effects on lung cancer incidence among atomic-bomb survivors. Radiat Res 174:72–82

    ADS  Google Scholar 

  • Furukawa K, Preston D, Funamoto S, Yonehara S, Ito M, Tokuoka S, Sugiyama H, Soda M, Ozasa K, Mabuchi K (2013) Long-term trend of thyroid cancer risk among Japanese atomic-bomb survivors: 60 years after exposure. Int J Cancer 132(5):1222–1226

    Google Scholar 

  • Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thurlimann B, Senn HJ, Panel M (2013) Personalizing the treatment of women with early breast cancer: highlights of the St Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2013. Ann Oncol 24(9):2206–2223. https://doi.org/10.1093/annonc/mdt303

    Article  Google Scholar 

  • Gomolka M, Blyth B, Bourguignon M, Badie C, Schmitz A, Talbot C, Hoeschen C, Salomaa S (2019) Potential screening assays for individual radiation sensitivity and susceptibility and their current validation state. Int J Radiat Biol. https://doi.org/10.1080/09553002.2019.1642544

    Article  Google Scholar 

  • Grant EJ, Brenner A, Sugiyama H, Sakata R, Sadakane A, Utada M et al (2017) Solid cancer incidence among the life span study of atomic bomb survivors: 1958–2009. Radiat Res 187(5):513–537

    ADS  Google Scholar 

  • Granzotto A, COPERNIC Project Investigators et al (2016) Influence of nucleoshuttling of the ATM protein in the healthy tissues response to radiation therapy: toward a molecular classification of human radiosensitivity. Int J Radiat Oncol Biol Phys 94:450–460

    Google Scholar 

  • Guleria A, Chandna S (2016) ATM kinase: Much more than a DNA damage responsive protein. DNA Repair (Amst) 39:1–20

    Google Scholar 

  • Hamasaki K et al (2016) Irradiation at different fetal stages results in different translocation frequencies in adult mouse thyroid cells. Radiat Res 186:360–366

    ADS  Google Scholar 

  • Hill DA, Gilbert E, Dores GM, Gospodarowicz M, van Leeuwen FE, Holowaty E, Glimelius B, Andersson M, Wiklund T, Lynch CF, Van't Veer M, Storm H, Pukkala E, Stovall M, Curtis RE, Allan JM, Boice JD, Travis LB (2005) Breast cancer risk following radiotherapy for Hodgkin lymphoma: modification by other risk factors. Blood 106(10):3358–3365. https://doi.org/10.1182/blood-2005-04-1535

    Article  Google Scholar 

  • Hirano S, Kakinuma S, Amasaki Y, Nishimura M, Imaoka T, Fujimoto S, Hino O, Shimada Y (2013) Ikaros is a critical target during simultaneous exposure to X-rays and N-ethyl-N-nitrosourea in mouse T-cell lymphomagenesis. Int J Cancer 132(2):259–268. https://doi.org/10.1002/ijc.27668

    Article  Google Scholar 

  • Hirayama T (1981) Non-smoking wives of heavy smokers have a higher risk of lung cancer: a study from Japan. BMJ 282:183–185

    Google Scholar 

  • Holmberg E, Holm LE, Lundell M, Mattsson A, Wallgren A, Karlsson P (2001) Excess breast cancer risk and the role of parity, age at first childbirth and exposure to radiation in infancy. Br J Cancer 85(3):362–366. https://doi.org/10.1054/bjoc.2001.1868

    Article  Google Scholar 

  • Holthusen H (1936) Erfahrungen über die Veträglichkeitsgrenze für Röntgenstrahlen und deren Nutzanwendung zur Verhütung von Schäden. Strahlentherapie 57:254–269

    Google Scholar 

  • Hsu WL, Preston DL, Soda M, Sugiyama H, Funamoto S, Kodama K, Kimura A, Kamada N, Dohy H, Tomonaga M, Iwanaga M, Miyazaki Y, Cullings HM, Suyama A, Ozasa K, Shore RE, Mabuchi K (2013) The incidence of leukemia, lymphoma and multiple myeloma among atomic bomb survivors: 1950–2001. Radiat Res 179(3):361–382. https://doi.org/10.1667/RR2892.1

    Article  ADS  Google Scholar 

  • Ianuzzi CM, Atencio DP, Green S, Stock RG, Rosenstein BS (2002) ATM mutations in female breast cancer patients predict for an increase in radiation-induced late effects. Int J Radiat Oncol Biol Phys 52:606–613. https://doi.org/10.1016/S0360-3016(01)02684-0

    Article  Google Scholar 

  • ICRP (1991) 1990 Recommendations of the international commission on radiological protection. ICRP Publication 60. Ann. ICRP 21(1–3):1–201

    Google Scholar 

  • ICRP (1998) genetic susceptibility to cancer. ICRP Publication 79. Ann ICRP 28(1–2):1–157

    Google Scholar 

  • ICRP (2003) Biological effects after prenatal irradiation (Embryo and Fetus). ICRP Publication 90. Ann. ICRP 33(1–2):5–206

    Google Scholar 

  • ICRP (2007) The 2007 recommendations of the international commission on radiological protection. ICRP Publication 103. Ann ICRP 37 (2–4)

  • ICRP (2018) Proceedings of the fourth international symposium on the system of radiological protection. Ann ICRP 47(3/4)

  • ICRP report on computational phantoms and radiation transport, paediatric reference computational phantoms, in press

  • ICRP report on The Use of Dose Quantities in Radiological Protection, in press.

  • Imaizumi M, Usa T, Tominaga T, Neriishi K, Akahoshi M, Nakashima E, Ashizawa K, Hida A, Soda M, Fujiwara S et al (2006) Radiation dose-response relationships for thyroid nodules and autoimmune thyroid diseases in Hiroshima and Nagasaki atomic bomb survivors 55–58 years after radiation exposure. JAMA 295(9):1011–1022

    Google Scholar 

  • Imaizumi M, Ohishi W, Nakashima E, Sera N, Neriishi K, Yamada M, Tatsukawa Y, Takahashi I, Fujiwara S, Sugino K et al (2015) Association of radiation dose with prevalence of thyroid nodules among atomic bomb survivors exposed in childhood (2007–2011). JAMA Intern Med 175(2):228–236

    Google Scholar 

  • Imaizumi M, Ohishi W, Nakashima E, Sera N, Neriishi K, Yamada M, Tatsukawa Y, Takahashi I, Fujiwara S, Sugino K et al (2017) Thyroid dysfunction and autoimmune thyroid diseases among atomic-bomb survivors exposed in childhood. J Clin Endocrinol Metab 102(7):2516–2524. https://doi.org/10.1210/jc.2017-00102

    Article  Google Scholar 

  • Imaoka T, Nishimura M, Teramoto A, Nishimura Y, Ootawara M, Osada H, Kakinuma S, Maekawa A, Shimada Y (2005) Cooperative induction of rat mammary cancer by radiation and 1-methyl-1-nitrosourea via the oncogenic pathways involving c-Myc activation and H-ras mutation. Int J Cancer 115(2):187–193

    Google Scholar 

  • Imaoka T, Nishimura M, Iizuka D, Nishimura Y, Ohmachi Y, Shimada Y (2011) Pre- and postpubertal irradiation induces mammary cancers with distinct expression of hormone receptors, ErbB ligands, and developmental genes in rats. Mol Carcinog 50(7):539–552. https://doi.org/10.1002/mc.20746

    Article  Google Scholar 

  • Imaoka T, Nishimura M, Daino K, Kokubo T, Doi K, Iizuka D, Nishimura Y, Okutani T, Takabatake M, Kakinuma S, Shimada Y (2013) Influence of age on the relative biological effectiveness of carbon ion radiation for induction of rat mammary carcinoma. Int J Radiat Oncol Biol Phys 85(4):1134–1140. https://doi.org/10.1016/j.ijrobp.2012.08.035

    Article  Google Scholar 

  • Imaoka T, Nishimura M, Doi K, Tani S, Ishikawa K, Yamashita S, Ushijima T, Imai T, Shimada Y (2014) Molecular characterization of cancer reveals interactions between ionizing radiation and chemicals on rat mammary carcinogenesis. Int J Cancer 134(7):1529–1538. https://doi.org/10.1002/ijc.28480

    Article  Google Scholar 

  • Imaoka T, Ishii N, Kawaguchi I, Homma-Takeda S, Doik K, Daino K, Nakanishi I, Tagami K, Kokubo T, Morioka T, Hosoki A, Takabatake M, Yoshinaga S (2016) Biological measures to minimize the risk of radiotherapy-associated second cancer: A research perspective. Int J Radiat Biol 92(6):289–301

    Google Scholar 

  • Imaoka T, Nishimura M, Daino K, Hosoki A, Takabatake M, Kokubo T, Doi K, Showler K, Nishimura Y, Moriyama H, Morioka T, Shimada Y, Kakinuma S (2017) Age modifies the effect of 2-MeV fast neutrons on rat mammary carcinogenesis. Radiat Res 188(4):419–425. https://doi.org/10.1667/RR14829.1

    Article  ADS  Google Scholar 

  • Imaoka T, Nishimura M, Daino K, Hosoki A, Takabatake M, Nishimura Y, Kokubo T, Morioka T, Doi K, Shimada Y, Kakinuma S (2018a) Prominent dose-rate effect and its age dependence of rat mammary carcinogenesis induced by continuous Gamma-ray exposure. Radiat Res. https://doi.org/10.1667/RR15094.1

    Article  Google Scholar 

  • Imaoka T, Nishimura M, Daino K, Takabatake M, Moriyama H, Nishimura Y, Morioka T, ShimadaY KS (2018b) Risk of second cancer after ion beam radiotherapy: insights from animal carcinogenesis studies. Int J Radiat Biol. https://doi.org/10.1080/09553002.2018.1547848

    Article  Google Scholar 

  • Imaoka T, Nishimura M, Daino K, Hosoki A, Takabatake M, Nishimura Y, Kokubo T, Morioka T, Doik K, Shimada Y, Kakinuma S (2019) Prominent dose-rate effect and its age dependence of rat mammary carcinogenesis induced by continuous gamma-ray exposure. Radiat Res 191(3):245–254. https://doi.org/10.1667/RR15094.1

    Article  Google Scholar 

  • Inoue T, Kokubo T, Daino K, Yanagihara H, Watanabe F, Tsuruoka C, Amasaki Y, Morioka T, Homma-Takeda S, Kobayashi T, Hino O, Shimada Y, Kakinuma S (2020) Interstitial chromosomal deletion of the Tsc2 locus is a signature for radiation-associated renal tumors in Eker rats. Cancer Sci. https://doi.org/10.1111/cas.14307

    Article  Google Scholar 

  • Ishida Y, Takabatake T, Kakinuma S, Doi K, Yamauchi K, Kaminishi M, Kito S, Ohta Y, Amasaki Y, Moritake H, Kokubo T, Nishimura M, Nishikawa T, Hino O, Shimada Y (2010) Genomic and gene expression signatures of radiation in medulloblastomas after low-dose irradiation in Ptch1 heterozygous mice. Carcinogenesis 31(9):1694–1701. https://doi.org/10.1093/carcin/bgq145

    Article  Google Scholar 

  • Ishikawa A, Suga T, Shoji Y, Kato S, Ohno T, Ishikawa H, Yoshinaga S, Ohara K, Ariga H, Nomura K, Shibamoto Y, Ishikawa K, Moritake T, Michikawa Y, Iwakawa M, Imai T (2011) Genetic variants of NPAT-ATM and AURKA are associated with an early adverse reaction in the gastrointestinal tract of patients with cervical cancer treated with pelvic radiation therapy. Int J Radiat Oncol Biol Phys 81(4):1144–1152

    Google Scholar 

  • Ishikawa H, Tsuji H, Kamada T et al (2006a) Risk factors of late rectal bleeding after carbon ion therapy for prostate cancer. Int J Radiat Oncol Biol Phys 66:1084–1091

    Google Scholar 

  • Ishikawa K, Koyama-Saegusa K, Otsuka Y, Ishikawa A, Kawai S, Yasuda K, Suga T, Michikawa Y, Suzuki M, Iwakawa M, Imai T (2006b) Gene expression profile changes correlating with radioresistance in human cell lines. Int J Radiat Oncol Biol Phys 65:234–245

    Google Scholar 

  • Iwakawa M, Noda A, Ohta T, Ohira C, Lee R et al (2003) Different radiation susceptibility among five strains of mice detected by a skin Reaction. J Radiat Res 44(1):7–13. https://doi.org/10.1269/jrr.44.7

    Article  Google Scholar 

  • Iwakawa M, Noda S, Ohta T, Oohira C, Tanaka H, Tsuji A, Ishikawa A, Imai T (2004) Strain dependent differences in a histological study of CD44 and collagen fibers with an expression analysis of inflammatory response-related genes in irradiated murine lung. J Radiat Res 45:423–433

    Google Scholar 

  • Iwakawa M, Noda S, Yamada S, Yamamoto N, Miyazawa Y, Yamazaki H, Kawakami Y, Matsui Y, Tsujii H, Mizoe J, Oda E, Fukunaga Y, Imai T (2006) Analysis of non-genetic risk factors for adverse skin reactions to radiotherapy among 284 breast cancer patients. Breast Cancer 13(3):300. https://doi.org/10.2325/jbcs.13.300

    Article  Google Scholar 

  • Joiner MC, van der Kogel AJ (eds) (2018) Basic clinical radiobiology, 5th edn. CRC Press Taylor and Francis Group, London

    Google Scholar 

  • Kakinuma S, Nishimura M, Amasaki Y, Takada M, Yamauchi K, Sudo S, Shang Y, Doi K, Yoshinaga S, Shimada Y (2012) Combined exposure to X-irradiation followed by N-ethyl-N-nitrosourea treatment alters the frequency and spectrum of Ikaros point mutations in murine T-cell lymphoma. Mutat Res 737:43–50. https://doi.org/10.1016/j.mrfmmm.2012.06.001

    Article  Google Scholar 

  • Kakinuma S, Yamauchi K, Amasaki Y, Nishimura M, Shimada Y (2009) Low-dose radiation attenuates chemical mutagenesis in vivo. J Radiat Res 50(5):401–405

    Google Scholar 

  • Kato S, Ohno T, Tsujii H et al (2006) Dose escalation study of carbon ion radiotherapy for locally advanced carcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys 65:388–397

    Google Scholar 

  • Kawaguchi I, Doi M, Kakinuma S, Shimada Y (2006) Combined effect of multiple carcinogens and synergy index. J Theor Biol 243(1):143–151. https://doi.org/10.1016/j.jtbi.2006.05.027

    Article  MathSciNet  Google Scholar 

  • Kerns SL, Stock R, Stone N, Buckstein M, Shao Y, Campbell C, Rath L, De Ruysscher D, Lammering G, Hixson R, Cesaretti J, Terk M, Ostrer H, Rosenstein BS (2013) A 2-stage genome-wide association study to identify single nucleotide polymorphisms associated with development of erectile dysfunction following radiation therapy for prostate cancer. Int J Radiat Oncol Biol Phys 85(1):e21–e28

    Google Scholar 

  • Kerns SL, Fachal L, Dorling L, Barnett GC, Baran A, Peterson DR, Hollenberg M, Hao K, Narzo AD, Ahsen ME, Pandey G, Bentzen SM, Janelsins M, Elliott RM, Pharoah PDP, Burnet NG, Dearnaley DP, Gulliford SL, Hall E, Sydes MR, Aguado-Barrera ME, Gómez-Caamaño A, Carballo AM, Peleteiro P, Lobato-Busto R, Stock R, Stone NN, Ostrer H, Usmani N, Singhal S, Tsuji H, Imai T, Saito S, Eeles R, DeRuyck K, Parliament M, Dunning AM, Vega A, Rosenstein BS, West CML (2019) Radiogenomics consortium genome-wide association study meta-analysis of late toxicity after prostate cancer radiotherapy. J Natl Cancer Inst. https://doi.org/10.1093/jnci/djz075

    Article  Google Scholar 

  • Kokubo T, Kakinuma S, Kobayashi T, Watanabe F, Iritani R, Tateno K, Nishimura M, Nishikawa T, Hino O, Shimada Y (2010) Age dependence of radiation-induced renal cell carcinomas in an Eker rat model. Cancer Sci 101(3):616–623. https://doi.org/10.1111/j.1349-7006.2009.01456.x

    Article  Google Scholar 

  • Kusunoki Y, Hayashi T (2008) Long-lasting alterations of the immune system by ionizing radiation exposure: implications for disease development among atomic bomb survivors. Int J Radiat Biol 84:1–14

    Google Scholar 

  • Lewontin R (2001) The triple helix: gene, organism and environment. Harvard University Press, Boston

    MATH  Google Scholar 

  • Li CI (2010) Chapter 2 Breast cancer biology and clinical characteristics. Breast cancer epidemiology. Springer, New York, pp 21–46

    Google Scholar 

  • Liang X, Weigand LU, Schuster IG, Eppinger E, van der Griendt JC, Schub A, Leisegang M, Sommermeyer D, Anderl F, Han Y, Ellwart J, Moosmann A, Busch DH, Uckert W, Peschel C, Krackhardt AM (2010) A single TCR alpha-chain with dominant peptide recognition in the allorestricted HER2/neu-specific T cell repertoire. J Immunol 184:1617–1629

    Google Scholar 

  • Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, Pukkala E, Skytthe A, Hemminki K (2000) Environmental and heritable factors in the causation of cancer–analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 343(2):78–85

    Google Scholar 

  • Lim A, Trautmann L, Peyrat MA, Couedel C, Davodeau F, Romagné F, Kourilsky P, Bonneville M (2000) Frequent contribution of T cell clonotypes with public TCR features to the chronic response against a dominant EBV-derived epitope: application to direct detection of their molecular imprint on the human peripheral T cell repertoire. J Immunol 165:2001–2011

    Google Scholar 

  • Lorat Y, Schanz S, Rübe CE (2016) Ultrastructural insights into the biological significance of persisting DNA damage foci after low doses of ionizing radiation. Clin Cancer Res 22(21):5300–5311

    Google Scholar 

  • Matsuo K, Ito H, Yatabe Y, Hiraki A, Hirose K, Wakai K, Kosaka T, Suzuki T, Tajima K, Mitsudomi T (2007) Risk factors differ for non-small-cell lung cancers with and without EGFR mutation: assessment of smoking and sex by a case-control study in Japanese. Cancer Sci 98(1):96–101

    Google Scholar 

  • Meier-Abt F, Bentires-Alj M, Rochlitz C (2015) Breast cancer prevention: lessons to be learned from mechanisms of early pregnancy-mediated breast cancer protection. Cancer Res. https://doi.org/10.1158/0008-5472.CAN-14-2717

    Article  Google Scholar 

  • Michikawa Y, Sugahara K, Suga T, Ohtsuka Y, Ishikawa K, Ishikawa A, Shiomi N, Shiomi T, Iwakawa M, Imai T (2008a) In-gel multiple displacement amplification of long DNA fragments diluted to the single molecule level. Anal Biochem 383:151–158

    Google Scholar 

  • Michikawa Y, Suga T, Ohtsuka Y, Matsumoto I, Ishikawa A, Ishikawa K, Iwakawa M, Imai T (2008b) Visible genotype sensor array. Sensors 8:2722–2735

    Google Scholar 

  • Miconnet I, Marrau A, Farina A, Taffé P, Vigano S, Harari A, Pantaleo G (2011) Large TCR diversity of virus-specific CD8 T cells provides the mechanistic basis for massive TCR renewal after antigen exposure. J Immunol 186:7039–7049

    Google Scholar 

  • Midha A, Dearden S, McCormack R (2015) EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity (mutMapII). Am J Cancer Res 5(9):2892–2911

    Google Scholar 

  • Miles JJ, Elhassen D, Borg NA, Silins SL, Tynan FE, Burrows JM, Purcell AW, Kjer-Nielsen L, Rossjohn J, Burrows SR, McCluskey J (2005) CTL recognition of a bulged viral peptide involves biased TCR selection. J Immunol 175:3826–3834

    Google Scholar 

  • Miyoshi-Imamura T, Kakinuma S, Kaminishi M, Okamoto M, Takabatake T, Nishimura Y, Imaoka T, Nishimura M, Murakami-Murofushi K, Shimada Y (2010) Unique characteristics of radiation-induced apoptosis in the postnatally developing small intestine and colon of mice. Radiat Res 173(3):310–318. https://doi.org/10.1667/RR1905.1

    Article  ADS  Google Scholar 

  • Morioka T, Miyoshi-Imamura T, Blyth BJ, Kaminishi M, Kokubo T, Nishimura M, Kito S, Tokairin Y, Tani S, Murakami-Murofushi K, Yoshimi N, Shimada Y, Kakinuma S (2015) Ionizing radiation, inflammation, and their interactions in colon carcinogenesis in Mlh1-deficient mice. Cancer Sci 106(3):217–226. https://doi.org/10.1111/cas.12591

    Article  Google Scholar 

  • Morimoto I, Yoshimoto Y, Sato K, Hamilton HB, Kawamoto S, Nagataki IMS (1987) Serum TSH, thyroglobulin, and thyroidal disorders in atomic bomb survivors exposed in youth: 30-year follow-up study. J Nucl Med 28(7):1115–1122

    Google Scholar 

  • Morton LM, Sampson JN, Armstrong GT, Chen TH, Hudson MM, Karlins E, Dagnall CL, Li SA, Wilson CL, Srivastava DK, Liu W, Kang G, Oeffinger KC, Henderson TO, Moskowitz CS, Gibson TM, Merino DM, Wong JR, Hammond S, Neglia JP, Turcotte LM, Miller J, Bowen L, Wheeler WA, Leisenring WM, Whitton JA, Burdette L, Chung C, Hicks BD, Jones K, Machiela MJ, Vogt A, Wang Z, Yeager M, Neale G, Lear M, Strong LC, Yasui Y, Stovall M, Weathers RE, Smith SA, Howell R, Davies SM, Radloff GA, Onel K, Berrington de González A, Inskip PD, Rajaraman P, Fraumeni JF Jr, Bhatia S, Chanock SJ, Tucker MA, Robison LL (2017) Genome-wide association study to identify susceptibility loci that modify radiation-related risk for breast cancer after childhood cancer. J Natl Cancer Inst 109(11):058. https://doi.org/10.1093/jnci/djx058

    Article  Google Scholar 

  • Mumbrekar KD, Bola Sadashiva SR, Kabekkodu SP, Fernandes DJ, Vadhiraja BM, Suga T, Shoji Y, Nakayama F, Imai T, Satyamoorthy K (2017) Genetic variants in CD44 and MAT1A confer susceptibility to acute skin reaction in breast cancer patients undergoing radiation therapy. Int J Radiat Oncol Biol Phys 97:118–127

    Google Scholar 

  • Nagataki S, Shibata Y, Inoue S, Yokoyama N, Izumi M, Shimaoka K (1994) Thyroid diseases among atomic bomb survivors in Nagasaki. JAMA 272(5):364–370

    Google Scholar 

  • Nakano M et al (2007) Chromosome aberrations do not persist in the lymphocytes or bone marrow cells of mice irradiated in utero or soon after birth. Radiat Res 167:693–702

    ADS  Google Scholar 

  • Nakano M et al (2014) Fetal irradiation of rats induces persistent translocations in mammary epithelial cells similar to the level after adult irradiation, but not in hematolymphoid cells. Radiat Res 181:172–176

    ADS  Google Scholar 

  • Naylor K, Li G, Vallejo AN, Lee WW, Koetz K, Bryl E, Witkowski J, Fulbright J, Weyand CM, Goronzy JJ (2005) The influence of age on T cell generation and TCR diversity. J Immunol 174(11):7446–7452

    Google Scholar 

  • NCRP (2015) Health effects of low doses of radiation: perspectives on integrating radiation biology and epidemiology (NCRP commentary No. 24). National Council on Radiation Protection and Measurements, Bethesda

    Google Scholar 

  • Noda S, Iwakawa M, Ohta T, Iwata M, Yang M, Goto M, Tanaka H, Harada Y, Imai T (2005) Inter-strain variance in late phase of erythematous reaction or leg contracture after local irradiation among three strains of mice. Cancer Detect Rev 29:376–382

    Google Scholar 

  • Okamoto M, Yonekawa H (2005) Intestinal tumorigenesis in Min mice is enhanced by X-irradiation in an age-dependent manner. J Radiat Res 46(1):83–91

    Google Scholar 

  • Okonogi N, Suzuki Y, Sato H et al (2008a) Combination therapy of intravenously injected microglia and radiation therapy prolongs survival in a rat model of spontaneous malignant glioma. Int J Radiat Oncol Biol Phys 102(3):601–608

    Google Scholar 

  • Okonogi N, Fukahori M, Wakatsuki M et al (2008b) Dose constraints in the rectum and bladder following carbon-ion radiotherapy for uterus carcinoma: a retrospective pooled analysis. Radiat Oncol 13(1):119. https://doi.org/10.1186/s13014-018-1061-7

    Article  Google Scholar 

  • Onishi M, Okonogi N, Oike T et al (2018) (2018) High linear energy transfer carbon-ion irradiation increases the release of the immune mediator high mobility group box 1 from human cancer cells. J Radiat Res 59(5):541–546

    Google Scholar 

  • Ohtaki K et al (2004) Human fetuses do not register chromosome damage inflicted by radiation exposure in lymphoid precursor cells except for a small but significant effect at low doses. Radiat Res 161:373–379

    ADS  Google Scholar 

  • Opstal-van Winden AWJ, de Haan HG, Hauptmann M, Schmidt MK, Broeks A, Russell NS, Janus CPM, Krol ADG, van der Baan FH, De Bruin ML, van Eggermond AM, Dennis J, Anton-Culver H, Haiman CA, Sawyer EJ, Cox A, Devilee P, Hooning MJ, Peto J, Couch FJ, Pharoah P, Orr N, Easton DF, Aleman BMP, Strong LC, Bhatia S, Cooke R, Robison LL, Swerdlow AJ, van Leeuwen FE (2019) Genetic susceptibility to radiation-induced breast cancer after Hodgkin lymphoma. Blood 133(10):1130–1139. https://doi.org/10.1182/blood-2018-07-862607

    Article  Google Scholar 

  • Parker LN, Belsky JL, Mandai T, Blot WJ, Kawate R (1973) Serum thyrotropin level and goiter in relation to childhood exposure to atomic radiation. J Clin Endocrinol Metab 37(5):797–804

    Google Scholar 

  • Pereira S et al (2018) Fast and binary assay for predicting radiosensitivity based on the theory of ATM nucleo-shuttling: development, validation, and performance. Int J Radiat Oncol Biol Phys 100:353–360

    Google Scholar 

  • Peto J (2001) Cancer epidemiology in the last century and the next decade. Nature 411(6835):390–395. https://doi.org/10.1038/35077256

    Article  ADS  Google Scholar 

  • Pollard JM, Gatti RA (2009) Clinical radiation sensitivity with DNA repair disorders: an overview. Int J Radiat Oncol Biol Phys 74:1323–1331

    Google Scholar 

  • Pomerantz MM, Freedman ML (2011) The genetics of cancer risk. Cancer J 17:416–422. https://doi.org/10.1097/PPO.0b013e31823e5387

    Article  Google Scholar 

  • Preston DL, Mattsson A, Holmberg E et al (2002) Radiation effects on breast cancer risk: a pooled analysis of eight cohorts. Radiat Res 158(2):220–235

    ADS  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):1–64

    ADS  Google Scholar 

  • Puck TT, Marcus PI (1956) Action of X-rays on mammalian cells. J Exp Med 103:273–284

    Google Scholar 

  • Qi Q, Liu Y, Cheng Y, Glanville J, Zhang D, Lee JY, Olshen RA, Weyand CM, Boyd SD, Goronzy JJ (2014) Diversity and clonal selection in the human T-cell repertoire. Proc Natl Acad Sci USA 111:13139–13144

    ADS  Google Scholar 

  • Rajaraman P, Hauptmann M, Bouffler S, Wojcik A (2018) Human individual radiation sensitivity and prospects for prediction. Ann ICRP 47(3–4):126–141. https://doi.org/10.1177/0146645318764091

    Article  Google Scholar 

  • Rothblum-Oviatt C, Wright J, Lefton-Greif MA, McGrath-Morrow SA, Crawford TO, Lederman HM (2016) Ataxia telangiectasia: a review. Orphanet J Rare Dis 11:159

    Google Scholar 

  • Rogacev KS, Seiler S, Zawada AM, Reichart B, Herath E, Roth D, Ulrich C, Fliser D, Heine GH (2011) CD14++CD16+ monocytes and cardiovascular outcome in patients with chronic kidney disease. Eur Heart J 32:84–92

    Google Scholar 

  • Ronckers CM, Erdmann CA, Land CE (2005) Radiation and breast cancer: a review of current evidence. Breast Cancer Res 7(1):21–32

    Google Scholar 

  • Rosenstein BS et al (2004) Radiogenomics: radiobiology enters the era of big data and team science. Int J Radiat Oncol Biol Phys 89:709–713

    Google Scholar 

  • Rübe CE, Grudzenski S, Kühne M, Dong X, Rief N, Löbrich M, Rübe C (2008a) DNA double-strand break repair of blood lymphocytes and normal tissues analysed in a preclinical mouse model: implications for radiosensitivity testing. Clin Cancer Res 14(20):6546–6555

    Google Scholar 

  • Rübe CE, Dong X, Kühne M, Fricke A, Kaestner L, Lipp P, Rübe C (2008b) DNA double-strand break rejoining in complex normal tissues. Int J Radiat Oncol Biol Phys 72(4):1180–1187

    Google Scholar 

  • Rübe CE, Fricke A, Wendorf J, Stützel A, Kühne M, Ong MF, Lipp P, Rübe C (2010a) Accumulation of DNA double-strand breaks in normal tissues after fractionated irradiation. Int J Radiat Oncol Biol Phys 76(4):1206–1213

    Google Scholar 

  • Rübe CE, Fricke A, Schneider R, Simon K, Kühne M, Fleckenstein J, Gräber S, Graf N, Rübe C (2010b) DNA repair alterations in children with pediatric malignancies: novel opportunities to identify patients at risk for high-grade toxicities. Int J Radiat Oncol Biol Phys 78(2):359–369

    Google Scholar 

  • Rühm W, Bottollier-Depois JF, Gilvin P, Harrison R, Knezevic Z, Lopez MA, Tanner R, Vargas A, Woda C (2018) The work programme of EURADOS on internal and external dosimetry. Ann ICRP 47(3–4):20–34

    Google Scholar 

  • Safwat A, Bentzen SM, Nielsen OS, Mahmoud HK, Overgaard J (1996) Repair capacity of mouse lung after total body irradiation alone or combined with cyclophosphamide. Radiother Oncol 40:249–257

    Google Scholar 

  • Sakata R, McGale P, Grant EJ, Ozasa K, Peto R, Darby SC (2012) Impact of smoking on overall mortality and life expectancy in Japanese smokers. BMJ 345:e7093

    Google Scholar 

  • Sakata R, Preston DL, Brenner AV, Sugiyama H, Grant EJ, Rajaraman P, Sadakane A, Utada M, Benjamin F, Cahoon EK, Mabuchi K, Ozasa K (2019) Radiation-related risk of cancers of the upper digestive tract among Japanese atomic bomb survivors. Radiat Res 192(3):331–344

    ADS  Google Scholar 

  • Sasaki S (1991) Influence of the age of mice at exposure to radiation on life-shortening and carcinogenesis. J Radiat Res 32(Suppl 2):73–85

    ADS  MathSciNet  Google Scholar 

  • Schuler N, Palm J, Kaiser M, Betten D, Furtwängler R, Rübe C, Graf N, Rübe CE (2014) DNA-damage foci to detect and characterize DNA repair alterations in children treated for pediatric malignancies. PLoS ONE 9(3):e91319

    ADS  Google Scholar 

  • Schuler N, Palm J, Schmitz S, Lorat Y, Rübe CE (2017) Increasing genomic instability during cancer therapy in a patient with Li-Fraumeni syndrome. Clin Transl Radiat Oncol 7:71–78

    Google Scholar 

  • Seibold P, Behrens S, Schmezer P, Helmbold I, Barnett G, Coles C, Yarnold J, Talbot CJ, Imai T, Azria D, Koch CA, Dunning AM, Burnet N, Bliss JM, Symonds RP, Rattay T, Suga T, Kerns SL, Bourgier C, Vallis KA, Sautter-Bihl ML, Claßen J, Debus J, Schnabel T, Rosenstein BS, Wenz F, West CM, Popanda O, Chang-Claude J (2015) XRCC1 polymorphism associated with late toxicity after radiation therapy in breast cancer patients. Int J Radiat Oncol Biol Phys 92:1084–1092

    Google Scholar 

  • Shang Y, Kakinuma S, Yamauchi K, Morioka T, Kokubo T, Tani S, Takabatake T, Kataoka Y, Shimada Y (2014) Cancer prevention by adult-onset calorie restriction after infant exposure to ionizing radiation in B6C3F1 male mice. Int J Cancer 135(5):1038–1047. https://doi.org/10.1002/ijc.28751

    Article  Google Scholar 

  • Shang Y, Kakinuma S, Yamauchi K, Morioka T, Kokubo T, Tani S, Takabatake T, Kataoka Y,

  • Shang Y, Sawa Y, Blyth BJ, Tsuruoka C, Nogawa H, Shimada Y, Kakinuma S (2017) Radiation exposure enhances hepatocyte proliferation in neonatal mice but not in adult mice. Radiat Res 188(2):235–241. https://doi.org/10.1667/RR14563.1

    Article  ADS  Google Scholar 

  • Shibamoto Y et al (2011) Single nucleotide polymorphisms associated with risk of adverse skin reactions to radiation in patients undergoing breast-conserving therapy: single-institution analysis. Int J Radiat Oncol Biol Phys 81(2):S757–S758

    Google Scholar 

  • Shimada Y, Yasukawa-Barnes J, Kim RY, Gould MN, Clifton KH (1994) Age and radiation sensitivity of rat mammary clonogenic cells. Radiat Res 137(1):118–123

    ADS  Google Scholar 

  • Shimada Y, Nishimura M, Amasaki Y, Shang Y, Yamauchi K, Sawai T, Hirano S, Imaoka T, Yamada Y, Takabatake T, Kakinuma S (2011) Interaction of low dose radiation and other factors. Health Phys 100(3):278–279

    Google Scholar 

  • Socolow EL, Hashizume A, Neriishi S, Niitani R (1963) Thyroid carcinoma in man after exposure to ionizing radiation. A summary of the findings in Hiroshima and Nagasaki. N Engl J Med 268:406–410

    Google Scholar 

  • Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, Hastie T, Eisen MB, van de Rijn M, Jeffrey SS, Thorsen T, Quist H, Matese JC, Brown PO, Botstein D, Lonning PE, Borresen-Dale AL (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA 98(19):10869–10874. https://doi.org/10.1073/pnas.191367098

    Article  ADS  Google Scholar 

  • Sroussi HY, Epstein JB, Bensadoun RJ et al (2017) Common oral complications of head and neck cancer radiation therapy: mucositis, infections, saliva change, fibrosis, sensory dysfunctions, dental caries, periodontal disease, and osteoradionecrosis. Cancer Med 6:2918–2931

    Google Scholar 

  • Stewart A, Webb J, Hewitt D (1958) A survey of childhood malignancies. Br Med J 1:1495–1508

    Google Scholar 

  • Suga T, Ishikawa A, Kohda M, Otsuka Y, Yamada S, Yamamoto N, Shibamoto Y, Ogawa Y, Nomura K, Sho K, Omura M, Sekiguchi K, Kikuchi Y, Michikawa Y, Noda S, Sagara M, Ohashi J, Yoshinaga S, Mizoe J, Tsujii H, Iwakawa M, Imai T (2007) Haplotype-based analysis of genes associated with risk of adverse skin reactions after radiotherapy in breast cancer patients. Int J Radiat Oncol Biol Phys 69:685–693

    Google Scholar 

  • Suga T, Iwakawa M, Tsuji H, Ishikawa H, Oda E, Noda S, Otsuka Y, Ishikawa A, Ishikawa K, Shimazaki J, Mizoe JE, Tsujii H, Imai T (2008) Influence of multiple genetic polymorphisms on genitourinary morbidity after carbon ion radiotherapy for prostate cancer. Int J Radiat Oncol Biol Phys 72:808–813

    Google Scholar 

  • Sugimura T, Wakabayashi K, Nakagama H, Nagao M (2004) Heterocyclic amines: mutagens/carcinogens produced during cooking of meat and fish. Cancer Sci 95(4):290–299

    Google Scholar 

  • Sunaoshi M, Amasaki Y, Hirano-Sakairi S, Blyth BJ, Morioka T, Kaminishi M, Shang Y, Nishimura M, Shimada Y, Tachibana A, Kakinuma S (2015) The effect of age at exposure on the inactivating mechanisms and relative contributions of key tumor suppressor genes in radiation-induced mouse T-cell lymphomas. Mutat Res 779:58–67. https://doi.org/10.1016/j.mrfmmm.2015.06.004

    Article  Google Scholar 

  • Takabatake M, Daino K, Imaoka T, Blyth BJ, Kokubo T, Nishimura Y, Showler K, Hosoki A, Moriyama H, Nishimura M, Kakinuma S, Fukushi M, Shimada Y (2018) Differential effect of parity on rat mammary carcinogenesis after pre- or post-pubertal exposure to radiation. Sci Rep 8(1):14325. https://doi.org/10.1038/s41598-018-32406-1

    Article  ADS  Google Scholar 

  • Tani S, Blyth BJ, Shang Y, Morioka T, Kakinuma S, Shimada Y (2016) A multi-stage carcinogenesis model to investigate caloric restriction as a potential tool for post-irradiation mitigation of cancer risk. J Cancer Prev 21(2):115–120. https://doi.org/10.15430/JCP.2016.21.2.115

    Article  Google Scholar 

  • Thacker J (1994) Cellular radiosensitivity in ataxia-telangiectasia. Int J Radiat Biol 66(6 Suppl):S87–96

    Google Scholar 

  • Thompson DE, Mabuchi K, Ron E, Soda M, Tokunaga M, Ochikubo S, Sugimoto S, Ikeda T, Terasaki M, Izume S, Pleston DL (2005) Cancer incidence in atomic bomb survivors. Part II: solid tumors, 1958–1987. Radiat Res 137:S17–S67

    Google Scholar 

  • Tsuji AB, Sudo H, Sugyo A, Otsuki M, Miyagishi M, Taira K, Imai T, Harada YN (2005) A fast, simple method for screening radiation susceptibility genes by RNA interference. Biochem Biophys Res Commun 333:1370–1377

    Google Scholar 

  • Tsuruoka C, Blyth BJ, Morioka T, Kaminishi M, Shinagawa M, Shimada Y, Kakinuma S (2016) Sensitive detection of radiation-induced medulloblastomas after acute or protracted gamma-ray exposures in Ptch1 heterozygous mice using a radiation-specific molecular signature. Radiat Res 186(4):407–414

    ADS  Google Scholar 

  • United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) (2013) Sources, effects and risks of ionizing radiation. United Nations, New York

    Google Scholar 

  • Upton AC et al (1960) Influence of age at time of irradiation on induction of leukemia and ovarian tumors in RF mice. Proc Soc Exp Biol Med 104:769–772

    Google Scholar 

  • Utada M, Brenner AV, Preston DL, Cologne JB, Sakata R, Sugiyama H, Sadakane A, Grant EJ, Cahoon EK, Ozasa K, Mabuchi K (2019) Radiation risks of uterine cancer in atomic bomb Survivors: 1958–2009. JNCI Cancer Spectrum 2:pky081

    Google Scholar 

  • van der Burg M, Ijspeert H, Verkaik NS et al (2009) A DNA-PKcs mutation in a radiosensitive T-B- SCID patient inhibits Artemis activation and nonhomologous end-joining. J Clin Investig 119(1):91–98

    Google Scholar 

  • Vogin G, Bastogne T, Bodgi L, Gillet-Daubin J, Canet A, Pereira S, Foray N (2018) The phosphorylated ATM immunofluorescence assay: a high-performance radiosensitivity assay to predict postradiation therapy overreactions. Int J Radiat Oncol Biol Phys 101:690–693

    Google Scholar 

  • Vrouwe MG, Elghalbzouri-Maghrani E, Meijers M et al (2007) Increased DNA damage sensitivity of Cornelia de Lange syndrome cells: evidence for impaired recombinational repair. Hum Mol Genet 16(12):1478–1487

    Google Scholar 

  • West C, Rosenstein BS (2010) Establishment of a radiogenomics consortium. Radiother Oncol 94:117–118

    Google Scholar 

  • Wojcik A, Bouffler S, Hauptmann M, Rajaraman P (2018) Considerations on the use of the terms radiosensitivity and radiosusceptibility. J Radiol Prot 38(3):N25–N29. https://doi.org/10.1088/1361-6498/aacb03

    Article  Google Scholar 

  • Yamada Y, Iwata KI, Blyth BJ, Doi K, Morioka T, Daino K, Nishimura M, Kakinuma S, Shimada Y (2017) Effect of age at exposure on the incidence of lung and mammary cancer after thoracic X-ray irradiation in wistar rats. Radiat Res 187(2):210–220

    ADS  Google Scholar 

  • Yamauchi K, Kakinuma S, Sudo S, Kito S, Ohta Y, Nohmi T, Masumura K, Nishimura M, Shimada Y (2008) Differential effects of low- and high-dose X-rays on N-ethyl-N-nitrosourea-induced mutagenesis in thymocytes of B6C3F1 gpt-delta mice. Mutat Res 640(1–2):27–37. https://doi.org/10.1016/j.mrfmmm.2007.12.001

    Article  Google Scholar 

  • Yoshida K, Inoue T, Nojima K, Hirabayashi Y, Sado T (1997) Calorie restriction reduces the incidence of myeloid leukemia induced by a single whole-body radiation in C3H/He mice. Proc Natl Acad Sci USA 94(6):2615–2619

    ADS  Google Scholar 

  • Yoshida K, Cologne JB, Cordova K, Misumi M, Yamaoka M, Kyoizumi S, Hayashi T, Robins H, Kusunoki Y (2017) Aging-related changes in human T-cell repertoire over 20 years delineated by deep sequencing of peripheral T-cell receptors. Exp Gerontol 96:29–37. https://doi.org/10.1016/j.exger.2017.05.015

    Article  Google Scholar 

  • Yoshida K, French B, Yoshida N, Hida A, Ohishi W, Kusunoki Y (2019) Radiation exposure and longitudinal changes in peripheral monocytes over 50 years: the Adult Health Study of atomic-bomb survivors. Br J Haematol 185(1):107–115. https://doi.org/10.1111/bjh.15750

    Article  Google Scholar 

  • Yoshimoto Y, Suzuki Y, Mimura K et al (2014) Radiotherapy-induced anti-tumor immunity contributes to the therapeutic efficacy of irradiation and can be augmented by CTLA-4 blockade in a mouse model. PLoS ONE 9(3):e92572

    ADS  Google Scholar 

  • Yoshimoto Y, Oike T, Okonogi N et al (2015) Carbon-ion beams induce production of an immune mediator protein, high mobility group box 1, at levels comparable with X-ray irradiation. J Radiat Res 56(3):509–514

    Google Scholar 

Download references

Acknowledgements

The workshop participants and members of ICRP Task Group 111 thank Christopher Clement, the ICRP Scientific Secretary for his support and participation at these workshops and his review and comments on this article. The Radiation Effects Research Foundation (RERF), Hiroshima and Nagasaki, Japan is a public interest foundation funded by the Japanese Ministry of Health, Labour and Welfare (MHLW) and the US Department of Energy (DOE). The research was also funded in part through DOE award DE-HS0000031 to the National Academy of Sciences and contract HHSN261201400009C through the U. S. National Cancer Institute (NCI). The views of the authors do not necessarily reflect those of the two governments. The study by A Sadakane is based on a collaboration with researchers outside RERF, Dr. Shuji Yonehara of JA Onomichi General Hospital, Dr. Takashi Nishisaka of Hiroshima Prefectural Hospital, Dr. Masahiro Nakashima of Nagasaki University, Dr. Dale L. Preston of HiroSoft International Corporation, and Dr. Kiyohiko Mabuchi, Dr. Xiaohong R. Yang, and Dr. Amy Berrington de Gonzalez of the US National Cancer Institute. This study is supported by the contract with US NCI (HHSN261201400009C) and by JSPS KAKENHI Grant Number JP23590839, in addition to the usual funds from Japanese and US governments.

Author information

Authors and Affiliations

  1. Zionsville, USA

    K. E. Applegate

  2. Helmholtz Center Munich, German Research Center for Environmental Health, Institute of Radiation Medicine, Neuherberg, Germany

    W. Rühm

  3. Centre for Radiation Protection Research, MBW Department, Stockholm University, Stockholm, Sweden

    A. Wojcik

  4. Department of Biophysics and Nuclear Medicine, University of Paris Saclay (UVSQ), Verseilles, France

    M. Bourguignon

  5. Department of Epidemiology, Radiation Effects Research Foundation, Hiroshima, Japan

    A. Brenner, K. Ozasa, A. Sadakane & R. Sakata

  6. Department of Molecular Biosciences, Radiation Effects Research Foundation, Hiroshima, Japan

    K. Hamasaki

  7. National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Sciences and Technology, Chiba, Japan

    T. Imai

  8. Department of Nagasaki Clinical Studies, Radiation Effects Research Foundation, Nagasaki, Japan

    M. Imaizumi

  9. Department of Radiation Effects Research, National Institute of Radiological Sciences, National Institute for Quantum and Radiological Science and Technology, Chiba, Japan

    T. Imaoka, S. Kakinuma & N. Nishimura

  10. QST Hospital, National Institute of Radiological Sciences, National Institute for Quantum and Radiological Science and Technology, Chiba, Japan

    T. Kamada & N. Okonogi

  11. Department of Radiation Oncology, Saarland University Medical Center, Homburg/Saar, Germany

    C. E. Rübe

  12. National Institute for Quantum and Radiological Science and Technology, Chiba, Japan

    Y. Shimada

  13. Immunology Laboratory, Department of Molecular Biosciences, Radiation Effects Research Foundation, Hiroshima, Japan

    K. Yoshida

  14. Radiation Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilto, Didcot, UK

    S. Bouffler

  15. Institute for Environmental Sciences, Aomori, Japan

    Y. Shimada

Authors
  1. K. E. Applegate
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. W. Rühm
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. Wojcik
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M. Bourguignon
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A. Brenner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K. Hamasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. T. Imai
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. M. Imaizumi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. T. Imaoka
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. S. Kakinuma
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. T. Kamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. N. Nishimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. N. Okonogi
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. K. Ozasa
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. C. E. Rübe
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. A. Sadakane
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. R. Sakata
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Y. Shimada
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. K. Yoshida
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. S. Bouffler
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Human Individual Radiation Sensitivity and Prospects for Prediction (AW); Longitudinal analyses of clinical data and biosamples (KY); Fetal hematopoietic stem cells are not at all sensitive to radiation for induction of persisting chromosome aberrations. How are the damaged cells eliminated? (KH); Recent Animal Studies in QST-NIRS on Individual radiation-related cancer risk (TI, MN, SK, YS); Age-dependence of breast cancer risk (AB); Intrinsic subtypes of radiation-associated breast cancers among female atomic bomb survivors (AS); Thyroid diseases following childhood exposure (MI); Upper gastrointestinal tract cancer among LSS participants (RS); Lifestyle-related Cancer Risk: Smoking and Cancer (KO); Genetic Variations in Individual Radiation Therapy Adverse Response (TI); Exceptional responders versus tissue effects in radiation therapy (NO, TK); Radiosensitivity and radiotherapy (MB); Normal tissue responses after exposure to low doses of ionizing radiation (CER).

Corresponding author

Correspondence to K. E. Applegate.

Ethics declarations

Conflict of interest

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

The International Commission of Radiological Protection (ICRP) has convened Task Group 111 to review the current science relevant to the topic of individual response to radiation. To begin this effort, ICRP held a series of workshops in December of 2018 with Japanese scientists at the National Institutes for Quantum and Radiological Science, and Technology (NIRS-QST) in Chiba, the Radiation Effects Research Foundation (RERF) in Hiroshima, and the National Cancer Centre in Tokyo to discuss key questions and issues raised. This paper provides summaries of the workshop contributions.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Applegate, K.E., Rühm, W., Wojcik, A. et al. Individual response of humans to ionising radiation: governing factors and importance for radiological protection. Radiat Environ Biophys 59, 185–209 (2020). https://doi.org/10.1007/s00411-020-00837-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00411-020-00837-y

Keywords

Search

Navigation