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Original Articles

Challenges in the quantification approach to a radiation relevant adverse outcome pathway for lung cancer

ORCID Icon, ORCID Icon, ORCID Icon, ORCID Icon & ORCID Icon
Pages 85-101 | Received 26 Feb 2020, Accepted 25 Aug 2020, Published online: 30 Sep 2020

References

  • Abe Y, Yoshida MA, Fujioka K, Kurosu Y, Ujiie R, Yanagi A, Tsuyama N, Miura T, Inaba T, Kamiya K, et al. 2018. Dose-response curves for analyzing of dicentric chromosomes and chromosome translocations following doses of 1000 mGy or less, based on irradiated peripheral blood samples from five healthy individuals. J Radiat Res. 59(1):35–42.
  • Adewoye AB, Lindsay SJ, Dubrova YE, Hurles ME. 2015. The genome-wide effects of ionizing radiation on mutation induction in the mammalian germline. Nat Commun. 6:6684.
  • Agostinelli S, Allison J, Amako K, Apostolakis J, Araujo H, Arce P, Asai M, Axen D, Banerjee S, Barrand G, et al. 2003. GEANT4 – a simulation toolkit. Nucl Instrum Methods in Phys Res A. 506(3):250–303.
  • Albertini RJ, Clark LS, Nicklas JA, O'Neill JP, Hui TE, Jostes R. 1997. Radiation quality affects the efficiency of induction and the molecular spectrum of HPRT mutations in human T cells. Radiat Res. 148(5):S76–S86.
  • Ankley GT, Bennett RS, Erickson RJ, Hoff DJ, Hornung MW, Johnson RD, Mount DR, Nichols JW, Russom CL, Schmieder PK, et al. 2010. Adverse outcome pathways: a conceptual framework to support ecotoxicology research and risk assessment. Environ Toxicol Chem. 29(3):730–741.
  • Antonelli F, Campa A, Esposito G, Giardullo P, Belli M, Dini V, Meschini S, Simone G, Sorrentino E, Gerardi S, et al. 2015. Induction and repair of DNA DSB as revealed by H2AX phosphorylation foci in human fibroblasts exposed to low- and high-LET radiation: relationship with early and delayed reproductive cell death. Radiat Res. 183(4):417–431.
  • Arlt MF, Rajendran S, Birkeland SR, Wilson TE, Glover TW. 2014. Copy number variants are produced in response to low-dose ionizing radiation in cultured cells. Environ Mol Mutagen. 55(2):103–113.
  • Balajee AS, Bertucci A, Taveras M, Brenner DJ. 2014. Multicolour FISH analysis of ionising radiation induced micronucleus formation in human lymphocytes. Mutagenesis. 29(6):447–455.
  • Barnhart BJ, Cox SH. 1979. Mutagenicity and cytotoxicity of 4.4-MeV alpha-particles emitted by plutonium-238. Radiat Res. 80(3):542–548.
  • Barquinero JF, Stephan G, Schmid E. 2004. Effect of americium-241 alpha-particles on the dose-response of chromosome aberrations in human lymphocytes analysed by fluorescence in situ hybridization. Int J Radiat Biol. 80(2):155–164.
  • Basheerudeen SAS, Kanagaraj K, Jose MT, Ozhimuthu A, Paneerselvam S, Pattan S, Joseph S, Raavi V, Perumal V. 2017. Entrance surface dose and induced DNA damage in blood lymphocytes of patients exposed to low-dose and low-dose-rate x-irradiation during diagnostic and therapeutic interventional radiology procedures. Mutat Res. 818:1–6.
  • Beels L, Bacher K, De Wolf D, Werbrouck J, Thierens H. 2009. Gamma-H2AX Foci as a biomarker for patient x-ray exposure in pediatric cardiac catheterization: are we underestimating radiation risks?. Circulation. 120(19):1903–1909.
  • Belli M, Cherubini R, Dalla Vecchia M, Dini V, Moschini G, Signoretti C, Simone G, Tabocchini MA, Tiveron P. 2000. DNA DSB induction and rejoining in V79 cells irradiated with light ions: a constant field gel electrophoresis study. Int J Radiat Biol. 76(8):1095–1104.
  • Berger MJ, Coursey JS, Zucker MA, Chang J. 2005. ESTAR, PSTAR, and ASTAR: Computer programs for calculating stopping-power and range tables for electrons, protons, and helium Ions (version 1.2.3). Gaithersburg, MD: National Institute of Standards and Technology. [Online] [accessed 2019 Jan 8]. http://physics.nist.gov/Star.
  • Bernal MA, Bordage MC, Brown JMC, Davídková M, Delage E, El Bitar Z, Enger SA, Francis Z, Guatelli S, Ivanchenko VN, et al. 2015. Track structure modeling in liquid water: a review of the Geant4-DNA very low energy extension of the Geant4 Monte Carlo simulation toolkit. Phys Med. 31(8):861–874.
  • Bilbao A, Prosser JS, Edwards AA, Moody JC, Lloyd DC. 1989. The induction of micronuclei in human lymphocytes by in vitro irradiation with alpha particles from plutonium-239. Int J Radiat Biol. 56(3):287–292.
  • Bolsunovsky A, Frolova T, Dementyev D, Sinitsyna O. 2016. Low doses of gamma-radiation induce SOS response and increase mutation frequency in Escherichia coli and Salmonella typhimurium cells. Ecotoxicol Environ Saf. 134P1:233–238.
  • Brooks AL. 1975. Chromosome damage in liver cells from low dose rate alpha, beta, and gamma irradiation: derivation of RBE. Science. 190(4219):1090–1092.
  • Brugmans MJP, Rispens SM, Bijwaard H, Laurier D, Rogel A, Tomasek L, Tirmarch M. 2004. Radon-induced lung cancer in French and Czech miner cohorts described with a two-mutation cancer model. Radiat Environ Biophys. 43(3):153–163.
  • Brun R, Rademakers F. 1997. ROOT - an object oriented data analysis framework. Nucl Instrum Methods Phys Res A. 389(1–2):81–86.
  • Canova S, Perin M, Mognato M, Favaretto S, Cherubini R, Celotti L. 2002. Minisatellite and HPRT mutations in V79 and human cells irradiated with gamma rays. Radiat Prot Dosimetry. 99(1–4):207–209.
  • Chancellor JC, Scott GBI, Sutton JP. 2014. Space radiation: the number one risk to astronaut health beyond low earth orbit. Life (Basel). 4(3):491–510.
  • Charlton DE, Nikjoo H, Humm JL. 1989. Calculation of initial yields of single- and double-strand breaks in cell nuclei from electrons, protons and alpha particles. Int J Radiat Biol. 56(1):1–19.
  • Chatzipapas KP, Papadimitroulas P, Emfietzoglou D, Kalospyros SA, Hada M, Georgakilas AG, Kagadis GC. 2020. Ionizing radiation and complex DNA damage: quantifying the radiobiological damage using Monte Carlo simulations. Cancers. 12(4):799.
  • Chauhan V, Sherman S, Said Z, Yauk CL, Stainforth R. 2020. A case example of a radiation-relevant adverse outcome pathway to lung cancer. Int J Radiat Biol. 1–17. DOI:https://doi.org/10.1080/09553002.2019.1704913
  • Chen DJ, Strniste GF, Tokita N. 1984. The genotoxicity of alpha particles in human embryonic skin fibroblasts. Radiat Res. 100(2):321–327.
  • Cornforth MN, Bailey SM, Goodwin EH. 2002. Dose responses for chromsome aberrations produced in noncycling primary human fibroblasts by alpha particles, and by gamma rays delivered at sublimating low dose rates. Radiat Res. 158(1):43–53.
  • Curwen GB, Tawn EJ, Cadwell KK, Guyatt L, Thompson J, Hill MA. 2012. mFISH analysis of chromosome aberrations induced in vitro by α-particle radiation: examination of dose-response relationships. Radiat Res. 178(5):414–424.
  • Darby S, Hill D, Auvinen A, Barros-Dios JM, Baysson H, Bochicchio F, Deo H, Falk R, Forastiere F, Hakama M, et al. 2005. Radon in homes and risk of lung cancer: collaborative analysis of individual data from 13 European case-control studies. BMJ. 330(7485):223.
  • de la Fuente Rosales L, Incerti S, Francis Z, Bernal MA. 2018. Accounting for radiation-induced indirect damage on DNA with the Geant 4-DNA code. Phys Med. 51:108–116.
  • de Lara CM, Hill MA, Jenner TJ, Papworth D, O'Neill P. 2001. Dependence of the Yield of DNA double-strand breaks in Chinese hamster V79-4 Cells on the photon energy of ultrasoft x rays. Radiat Res. 155(3):440–448.
  • Doughty MJ, Bergmanson JPG. 2004. Heterogeneity in the ultrastructure of the mucous (goblet) cells of the rabbit palpebral conjunctiva. Clin Exp Optom. 87(6):377–385.
  • DuFrain RJ, Littlefield G, Joiner EE, Frome EL. 1979. Human cytogenetic dosimetry: a dose-response relationship for alpha particle radiation from 241Am. Health Phys. 37(3):279–289.
  • Durante M, Grossi GF, Napolitano M, Pugliese M, Gialanella G. 1992. Chromosome damage induced by high-LET alpha-particles in plateau-phase C3H 10T1/2 cells. Int J Radiat Biol. 62(5):571–580.
  • Edwards AA, Purrott RJ, Prosser JS, Lloyd DC. 1980. The induction of chromosome aberrations in human lymphocytes by alpha-radiation. Int J Radiat Biol Relat Stud Phys Chem Med. 38(1):83–91.
  • Franken NAP, Hovingh S, Cate RT, Krawczyk P, Stap J, Hoebe R, Aten J, Barendsen GW. 2012. Relative biological effectiveness of high linear energy transfer alpha-particles for the induction of DNA-double-strand breaks, chromosome aberrations and reproductive cell death in SW-1573 lung tumour cells. Oncol Rep. 27:769–774.
  • Frankenberg D, Brede HJ, Schrewe UJ, Steinmetz C, Frankenberg-Schwager M, Kasten G, Pralle E. 1999. Induction of DNA double-strand breaks by 1H and 4He ions in primary human skin fibroblasts in the LET range of 8 to 124 keV/µm. Radiat Res. 151(5):540–549.
  • Friedland W, Dingfelder M, Jacob P, Paretzke HG. 2005. Calculated DNA double-strand break and fragmentation yields after irradiation with He ions. Radiat Phys Chem. 72(2–3):279–286.
  • Friedland W, Dingfelder M, Kundrat P, Jacob P. 2011. Track structures, DNA targets and radiation effects in the biophysical Monte Carlo simulation code PARTRAC. Mutat Res. 711(1–2):28–40.
  • Friedland W, Jacob P, Kundrát P. 2010. Stochastic simulation of DNA double-strand break repair by non-homologous end joining based on track structure calculations. Radiat Res. 173(5):677–688.
  • Friedland W, Schmitt E, Kundrát P, Dingfelder M, Baiocco G, Barbieri S, Ottolenghi A. 2017. Comprehensive track-structure based evaluation of DNA damage by light ions from radiotherapy-relevant energies down to stopping. Sci Rep. 7:45161.
  • George KA, Hada M, Jackson LJ, Elliott T, Kawata T, Pluth JM, Cucinotta FA. 2009. Dose response of gamma rays and iron nuclei for induction of chromosomal aberrations in normal and repair-deficient cell lines. Radiat Res. 171(6):752–763.
  • Goodhead DT. 2009. Fifth Warren K. Sinclair keynote address: issues in quantifying the effects of low-level radiation. Health Phys. 97(5):394–406.
  • Gossen JA, Martus HJ, Wei Y, Vijg J. 1995. Spontaneous and x-ray-induced deletion mutations in a LacZ plasmid-based transgenic mouse model. Mut Res. 331(1):89–97.
  • Grudzenski S, Raths A, Conrad S, Rübe CE, Löbrich M. 2010. Inducible response required for repair of low-dose radiation damage in human fibroblasts. Proc Natl Acad Sci USA. 107(32):14205–14210.
  • Hamza VZ, Mohankumar MN. 2009. Cytogenetic damage in human blood lymphocytes exposed in vitro to radon. Mutat Res. 661(1–2):1–9.
  • Han L, Zhao FL, Sun QF, Wang P, Wang XA, Guo F, Fu BH, Lü YM. 2014. Cytogenetic analysis of peripheral blood lymphocytes, many years after exposure of workers to low-dose ionizing radiation. Mutat Res Genet Toxicol Environ Mutagen. 771:1–5.
  • Hei TK, Wu LJ, Liu SX, Vannais D, Waldren CA, Randers-Pehrson G. 1997. Mutagenic effects of a single and an exact number of alpha particles in mammalian cells. Proc Natl Acad Sci USA. 94:1765–3770.
  • Heidenreich WF, Tomásek L, Rogel A, Laurier D, Tirmarche M. 2004. Studies of radon-exposed miner cohorts using a biologically based model: comparison of current Czech and French data with historic data from China and Colorado. Radiat Environ Biophys. 43(4):247–256.
  • [ICRP] International Commission on Radiological Protection. 1994. Human respiratory tract model for radiological protection. ICRP Publication 66. Ann ICRP. 24(1–3):13–16.
  • [ICRP] International Commission on Radiological Protection. 2007. The 2007 recommendations of the international commission on radiological protection. ICRP publication 103. Ann ICRP. 37 (2–4):63–65.
  • [ICRP] International Commission on Radiological Protection. 2017. Occupational intakes of radionuclides: part 3. ICRP Publication 137. Ann ICRP. 46(3–4):314–317.
  • Incerti S, Baldacchino G, Bernal M, Capra R, Champion C, Francis Z, Guèye P, Mantero A, Mascialino B, Moretto P, et al. 2010. The Geant4-DNA project. Int J Model Simul Sci Comput. 01 (02):157–178.
  • Incerti S, Ivanchenko A, Karamitros M, Mantero A, Moretto P, Tran HN, Mascialino B, Champion C, Ivanchenko VN, Bernal MA, et al. 2010. Comparison of Geant4 very low energy cross section models with experimental data in water. Med Phys. 37(9):4692–4708.
  • Incerti S, Kyriakou I, Bernal MA, Bordage MC, Francis Z, Guatelli S, Ivanchenko V, Karamitros M, Lampe N, Lee SB, et al. 2018. Geant4-DNA example applications for track structure simulations in liquid water: a report from the Geant4-DNA project. Med Phys. 45(8):e722–e739.
  • Jang MA, Han EA, Lee JK, Cho KH, Shin HB, Lee YK. 2019. Dose estimation curves following in vitro x-ray irradiation using blood from four healthy Korean individuals. Ann Lab Med. 39(1):91–95.
  • Karthik K, Rajan V, Pandey BN, Sivasubramanian K, Paul SFD, Venkatachalam P. 2019. Direct and bystander effects in human blood lymphocytes exposed to 241Am alpha particles and the relative biological effectiveness using chromosomal aberration and micronucleus assay. Int J Radiat Biol. 95(6):725–736.
  • Kuefner MA, Grudzenski S, Schwab SA, Wiederseiner M. 2009. DNA double-strand breaks and their repair in blood lymphocytes of patients undergoing angiographic procedures. Investig Radiol. 44(8):440–446.
  • Kühne M, Urban G, Frankenberg D, Löbrich M. 2005. DNA double-strand break misrejoining after exposure of primary human fibroblasts to CK characteristic x-rays, 29 kVp x-rays and Co γ-rays. Radiat Res. 164(5):669–676.
  • Loucas BD, Durante M, Bailey SM, Cornforth MN. 2013. Chromosome damage in human cells by γ rays, α particles and heavy ions: track interactions in basic dose-response relationships. Radiat Res. 179(1):9–20.
  • Lubin JH, Boice JD Jr, Edling C, Hornung RW, Howe GR, Kunz E, Kusiak RA, Morrison HI, Radford EP, Samet JM. 1995. Lung cancer in radon-exposed miners and estimation of risk from indoor exposure. J Natl Cancer Inst. 87(11):817–827.
  • Maffei F, Angelini S, Forti GC, Violante FS, Lodi V, Mattioli S, Hrelia P. 2004. Spectrum of chromosomal aberrations in peripheral lymphocytes of hospital workers occupationally exposed to low doses of ionizing radiation. Mutat Res. 547(1–2):91–99.
  • Masumura K, Kuniya K, Kurobe T, Fukuoka M, Yatagai F, Nohmi T. 2002. Heavy-ion-induced mutations in the gpt delta transgenic mouse: comparison of mutation spectra induced by heavy-ion, x-ray, and gamma-ray radiation. Environ Mol Mutagen. 40(3):207–215.
  • Matuo Y, Izumi Y, Furusawa Y, Shimizu K. 2018. Biological effects of carbon ion beams with various LETs on budding yeast Saccharomyces cerevisiae. Mutat Res. 810:45–51.
  • McMahon SJ, Schuemann J, Paganetti H, Prise KM. 2016. Mechanistic modelling of DNA repair and cellular survival following radiation-induced DNA damage. Sci Rep. 6:33290.
  • McNamara AL, Ramos-Méndez J, Perl J, Held K, Dominguez N, Moreno E, Henthorn NT, Kirkby KJ, Meylan S, Villagrasa C, et al. 2018. Geometrical structures for radiation biology research as implemented in the TOPAS-nBio toolkit. Phys Med Biol. 63(17):175018.
  • Meenakshi C, Mohankumar MN. 2013. Synergistic effect of radon in blood cells of smokers – an in vitro study. Mutat Res. 757(1):79–82.
  • Meenakshi C, Sivasubramanian K, Venkatraman B. 2017. Nucleoplasmic bridges as a biomarker of DNA damage exposed to radon. Mutat Res. 814:22–28.
  • Mestres M, Caballin MR, Schmid E, Stephan E, Stephan G, Sachs R, Barrios L, Barquinero JF. 2004. Analysis of alpha-particle induced chromosome aberrations in human lymphocytes, using pan-centromeric and pan-telomeric probes. Int J Radiat Biol. 80(10):737–744.
  • Metting NF, Palayoor ST, Macklis RM, Atcher RW, Liber HL, Little JB. 1992. Induction of mutations by bismuth-212 alpha particles at two genetic loci in human B-lymphoblasts. Radiat Res. 132(3):339–345.
  • Mill AJ, Wells J, Hall SC, Butler A. 1996. Micronucleus induction in human lymphocytes: comparative effects of X rays, alpha particles, beta particles and neutrons and implications for biological dosimetry. Radiat Res. 145(5):575–585.
  • Moeini H, Mokari M, Alamatsaz MH, Taleei R. 2020. Calculation of the initial DNA damage induced by alpha particles in comparison with protons and electrons using Geant4-DNA. Int J Radiat Biol. 96(6):767–778.
  • Moquet JE, Fernandex JL, Edwards AA, Lloyd DC. 2001. lymphocytes chromsomal aberrations and their complexity induced in vitro by plutonium-239 alpha-particles and detected by FISH. Cell Mol Biol. 47(3):549–556.
  • Morgan TL, Fleck EW, Poston KA, Denovan BA, Newman CN, Rossiter BJF, Miller JH. 1990. Molecular characterization of x-ray-induced mutations at the HPRT locus in plateau-phase Chinese hamster ovary cells. Mutat Res/Fundam Mol Mech Mutagen. 232(2):171–182.
  • Nagasawa H, Little JB, Inkret WC, Carpenter S, Thompson K, Raju MR, Chen DJ, Strniste GF. 1990. Cytogenetic effects of extremely low doses of plutonium-238 alpha-particle irradiation in CHO K-1 cells. Mutat Res. 244(3):233–238.
  • Nagasawa H, Little JB. 1999. Unexpected sensitivity to the induction of mutations by very low doses of alpha-particle radiation: evidence for a bystander effect. Radiat Res. 152(5):552–557.
  • Nagasawa H, Robertson J, Little JB. 1990. Induction of chromosomal aberrations and sister chromatid exchanges by alpha particles in density-inhibited cultures of mouse 10T1/2 and 3T3 cells. Int J Radiat Biol. 57(1):35–44.
  • Nagashima H, Shiraishi K, Ohkawa S, Sakamoto Y, Komatsu K, Matsuura S, Tachibana A, Tauchi H. 2018. Induction of somatic mutations by low-dose x-rays: the challenge in recognizing radiation-induced events. J Radiat Res. 59(suppl_2):ii11–ii17.
  • Nikjoo H, O'Neill P, Wilson WE, Goodhead DT. 2001. Computational approach for determining the spectrum of DNA damage induced by ionizing radiation. Radiat Res. 156(5 Pt 2):577–583.
  • [OECD] Organisation for Economic Co-operation and Development. 2017. Revised guidance document on developing and assessing adverse outcome pathways. Series on testing and assessment No. 184. Paris:OECD Environment, Health and Safety Publications.
  • [OECD] Organisation for Economic Co-operation and Development 2018. Users’ handbook supplement to the guidance document for developing and assessing AOPs. Series on adverse outcome pathways No. 1. Paris:OECD.
  • Oki NO, Nelms MD, Bell SM, Mortensen HM, Edwards SW. 2016. Accelerating adverse outcome pathway development using publicly available data sources. Curr Environ Health Rep. 3(1):53–63.
  • Perkins EJ, Ashauer R, Burgoon L, Conolly R, Landesmann B, Mackay C, Murphy CA, Pollesch N, Wheeler JR, Zupanic A, et al. 2019. Building and applying quantitative adverse outcome pathway models for chemical hazard and risk assessment. Environ Toxicol Chem. 38(9):1850–1865.
  • Perl J, Shin J, Schumann J, Faddegon B, Paganetti H. 2012. TOPAS: an innovative proton Monte Carlo platform for research and clinical applications. Med Phys. 39(11):6818–6837.
  • Preston RJ. 2015. Integrating basic radiobiological science and epidemiological studies: why and how. Health Phys. 108(2):125–130.
  • Puig R, Pujol M, Barrios L, Caballin MR, Barquinero J-F. 2016. Analysis of α-particle-induced chromosomal aberrations by chemically-induced PCC. Elaboration of dose-effect curves. Int J Radiat Biol. 92(9):493–501.
  • Purrott RJ, Edwards AA, Lloyd DC, Stather JW. 1980. The induction of chromosome aberrations in human lymphocytes by in vitro irradiation with alpha-particles from plutonium-239. Int J Radiat Biol. 38(3):277–284.
  • Qian QZ, Cao XK, Shen FH, Wang Q. 2016. Effects of ionising radiation on micronucleus formation and chromosomal aberrations in Chinese radiation workers. Radiat Prot Dosimetry. 168(2):197–203.
  • Ramkissoon A, Navaranjan G, Berriault C, Villeneuve PJ, Demers PA, Do MT. 2018. Histopathologic analysis of lung cancer incidence associated with radon exposure among Ontario uranium miners. Int J Environ Res Public Health. 15(11):2413.
  • Rogakou EP, Boon C, Redon C, Bonner WM. 1999. Megabase chromatin domains involved in DNA double-strand breaks in vivo. J Cell Biol. 146(5):905–916.
  • Rohatgi A. 2019. WebPlotDigitizer 4.2. [accessed 2020 Jan 10]. automeris.io/WebPlotDigitizer
  • 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 USA. 100(9):5057–5062.
  • Rübe CE, Grudzenski S, Kühne M, Dong X, Rief N, Löbrich M, Rübe C. 2008. 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):6546–6556.
  • Russell WL, Russell LB, Kelly EM. 1958. Radiation dose rate and mutation frequency. Science. 128(3338):1546–1550.
  • Rydberg B, Heilbronn L, Holley WR, Löbrich M, Zeitlin C, Chatterjee A, Cooper PK. 2002. Spatial distribution and yield of DNA double-strand breaks induced by 3-7 MeV helium ions in human fibroblasts. Radiat Res. 158(1):32–42.
  • Schmid E, Hieber L, Heinzmann U, Roos H, Kellerer AM. 1996. Analysis of chromosome aberrations in human peripheral lymphocytes induced by in vitro alpha-particle irradiation. Radiat Environ Biophys. 35(3):179–184.
  • Schmid E, Regulla D, Kramer H, Harder D. 2002. The effect of 29 kV x rays on the dose response of chromosome aberrations in human lymphocytes. Radiat Res. 158(6):771–777.
  • Schuemann J, McNamara AL, Ramos-Méndez J, Perl J, Held KD, Paganetti H, Incerti S, Faddegon B. 2019. TOPAS-nBio: an extension to the TOPAS simulation toolkit for cellular and sub-cellular radiobiology. Radiat Res. 191(2):125–138.
  • Schwartz JL, Ashman CR, Atcher RW, Sedita BA, Shadley JD, Tang J, Whitlock JL, Rotmensch J. 1991. Differential locus sensitivity to mutation induction by ionizing radiations of different LETs in Chinese hamster ovary K1 cells. Carcinogenesis. 12(9):1721–1726.
  • Schwartz JL, Jordan R, Sun J, Ma H, Hsieb AW. 2000. Dose-dependent changes in the spectrum of mutations induced by ionizing radiation. Radiat Res. 153(3):312–317.
  • Stewart RD, Streitmatter SW, Argento DC, Kirkby C, Goorley JT, Moffitt G, Jevremovic T, Sandison GA. 2015. Rapid MCNP simulation of DNA double strand break (DSB) relative biological effectiveness (RBE) for photons, neutrons, and light ions. Phys Med Biol. 60(21):8249–8274.
  • Sun HB, Shen J, Yokota H. 2000. Size-dependent positioning of human chromosomes in interphase nuclei. Biophys J. 79(1):184–190.
  • Suto Y, Akiyama M, Noda T, Hirai M. 2015. Construction of a cytogenetic dose-response curve for low-dose range gamma-irradiation in human peripheral blood lymphocytes using three-color FISH. Mutat Res Genet Toxicol Environ Mutagen. 794:32–38.
  • Suzuki K, Hei TK. 1996. Mutation induction in gamma-irradiated primary human bronchial epithelial cells and molecular analysis of the HPRT- mutants. Mutat Res. 349(1):33–41.
  • Takatsuji T, Sasaki MS. 1984. Dose-effect relationship of chromsome aberrations induced by 23 MeV alpha particles in human lymphocytes. Int J Radiat Biol. 45(3):237–243.
  • Tawn EJ, Thierens H. 2009. Dose response relationships for chromsome aberrations induced by low doses of alpha-particle radiation. Radiat Prot Dosim. 135(4):268–271.
  • Testa A, Ballarini F, Giesen U, Gil OM, Carante MP, Tello J, Langner F, Rabus H, Palma V, Pinto M, Patrono C. 2018. Analysis of radiation-induced chromosomal aberrations on a cell-by-cell basis after alpha-particle microbeam irradiation: experimental data and simulations. Radiat Res. 189(6):597–604.
  • Thacker J, Stretch A, Goodhead DT. 1982. The mutagenicity of alpha-particle from plutonium-238. Radiat Res. 92(2):343–352.
  • Themis M, Garimberti E, Hill MA, Anderson RM. 2013. Reduced chromosome aberration complexity in normal human bronchial epithelial cells exposed to low-LET γ-rays and high-LET α-particles. Int J Radiat Biol. 89(11):934–943.
  • Thomas P, Umegaki K, Fenech M. 2003. Nucleoplasmic bridges are a sensitive measure of chromosome rearrangement in the cytokinesis-block micronucleus assay. Mutagen. 18(2):187–194.
  • Tucker JD, Cofield J, Matsumoto K, Ramsey MJ, Freeman DC. 2005. Persistence of chromosome aberrations following acute radiation: I, PAINT translocations, dicentrics, rings, fragments, and insertions. Environ Mol Mutagen. 45(2–3):229–248.
  • Villeneuve DL, Crump D, Garcia-Reyero N, Hecker M, Hutchinson TH, LaLone CA, Landesmann B, Lettieri T, Munn S, Nepelska M, et al. 2014. Adverse outcome pathway (AOP) development I: strategies and principles. Toxicol Sci. 142(2):312–320.
  • Winegar RA, Lutze LH, Hamer JD, O'Loughlin KG, Mirsalis JC. 1994. Radiation-induced point mutations, deletions and micronuclei in lacI transgenic mice. Mutat Res. 307(2):479–487.
  • Wittwehr C, Aladjov H, Ankley G, Byrne HJ, de Knecht J, Heinzle E, Klambauer G, Landesmann B, Luijten M, MacKay C, et al. 2017. How adverse outcome pathways can aid the development and use of computational prediction models for regulatory toxicology. Toxicol Sci. 155(2):326–336.
  • Wu LJ, Randers-Pehrson G, Xu A, Waldren CA, Geard CR, Yu ZL, Hei TK. 1999. Targeted cytoplasmic irradiation with alpha particles induces mutations in mammalian cells. Proc Natl Acad Sci USA. 96(9):4959–4964.
  • Zgheib E, Gao W, Limonciel A, Aladjov H, Yang H, Tebby C, Gayraud G, Jennings P, Sachana M, Beltman JB, et al. 2019. Application of three approaches for quantitative AOP development to renal toxicity. Comput Toxicol. 11:1–3.
  • Zhu LX, Waldren CA, Vannias D, Hei TK. 1996. Cellular and molecular analysis of mutagenesis induced by charged particles of defined linear energy transfer. Radiat Res. 145(3):251–259.

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