Document Type: Blackboard


1 School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran

2 Department of Radiology, School of Paramedical, Shiraz University of Medical Sciences, Shiraz, Iran

3 Department of Medical Physics, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

4 Department of Radiology, Faculty of Paramedical, Tehran University of Medical Sciences, Tehran, Iran

5 Department of Medical Physics, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

6 Radiology and Nuclear Medicine Department, School of Paramedical Sciences, Kermanshah University of Medical Science, Kermanshah, Iran


Bystander or non-targeted effect is known to be an interesting phenomenon in radiobiology. The genetic consequences of bystander effect on non-irradiated cells have shown that this phenomenon can be considered as one of the most important factors involved in secondary cancer after exposure to ionizing radiation. Every year, millions of people around the world undergo radiotherapy in order to cure different types of cancers. The most crucial aim of radiotherapy is to improve treatment efficiency by reducing early and late effects of exposure to clinical doses of radiation. Secondary cancer induction resulted from exposure to high doses of radiation during treatment can reduce the effectiveness of this modality for cancer treatment. The perception of carcinogenesis risk of bystander effects and factors involved in this phenomenon might help reduce secondary cancer incidence years after radiotherapy. Different modalities such as radiation LET, dose and dose rate, fractionation, types of tissue, gender of patients, etc. may be involved in carcinogenesis risk of bystander effects. Therefore, selecting an appropriate treatment modality may improve cost-effectiveness of radiation therapy as well as the quality of life in survived patients. In this review, we first focus on the carcinogenesis evidence of non-targeted effects in radiotherapy and then review physical and biological factors that may influence the risk of secondary cancer induced by this phenomenon.


  1. Khosroabadi M, Farhood B, Ghorbani M, Hamzian N, Moghaddam HR, Davenport D. Tissue composition effect on dose distribution in neutron brachytherapy/neutron capture therapy. Rep Pract Oncol Radiother. 2016;21:8-16. PubMed PMID: 26900352. PubMed PMCID: 4716403.
  2. Gotay CC, Muraoka MY. Quality of life in long-term survivors of adult-onset cancers. J Natl Cancer Inst. 1998;90:656-67. PubMed PMID: 9586662.
  3. Narmani A, Farhood B, Haghi-Aminjan H, Mortezazadeh T, Aliasgharzadeh A, Mohseni M, et al. Gadolinium nanoparticles as diagnostic and therapeutic agents: Their delivery systems in magnetic resonance imaging and neutron capture therapy. J Drug Deliv Sci Technol. 2018;44:457-66.
  4. Widel M. Radiation Induced Bystander Effect: From in Vitro Studies to Clinical Application. International Journal of Medical Physics, Clinical Engineering and Radiation Oncology. 2016;5:1.
  5. Najafi M, Motevaseli E, Shirazi A, Geraily G, Rezaeyan A, Norouzi F, et al. Mechanisms of inflammatory responses to radiation and normal tissues toxicity: clinical implications. Int J Radiat Biol. 2018;94(4):335-56.
  6. Mancuso M, Pasquali E, Leonardi S, Tanori M, Rebessi S, Di Majo V, et al. Oncogenic bystander radiation effects in Patched heterozygous mouse cerebellum. Proc Natl Acad Sci U S A. 2008;105:12445-50. PubMed PMID: 18711141. PubMed PMCID: 2517601.
  7. Yahyapour R, Motevaseli E, Rezaeyan A, Abdollahi H, Farhood B, Cheki M, et al. Reduction-oxidation (redox) system in radiation-induced normal tissue injury: molecular mechanisms and implications in radiation therapeutics. Clin Transl Oncol. 2018;20:975–88. doi:10.1007/s12094-017-1828-6.
  8. Bostrom PJ, Soloway MS. Secondary cancer after radiotherapy for prostate cancer: should we be more aware of the risk? Eur Urol. 2007;52:973-82. PubMed PMID: 17644245.
  9. Joung JY, Lim J, Oh CM, Jung KW, Cho H, Kim SH, et al. Risk of Second Primary Cancer among Prostate Cancer Patients in Korea: A Population-Based Cohort Study. PLoS One. 2015;10:e0140693. PubMed PMID: 26469085. PubMed PMCID: 4607403.
  10. Brenner DJ, Curtis RE, Hall EJ, Ron E. Second malignancies in prostate carcinoma patients after radiotherapy compared with surgery. Cancer. 2000;88:398-406.;2-V. PubMed PMID: 10640974.
  11. Kleinerman RA, Boice JD, Jr., Storm HH, Sparen P, Andersen A, Pukkala E, et al. Second primary cancer after treatment for cervical cancer. An international cancer registries study. Cancer. 1995;76:442-52.;2-L. PubMed PMID: 8625126.
  12. Birgisson H, Pahlman L, Gunnarsson U, Glimelius B. Occurrence of second cancers in patients treated with radiotherapy for rectal cancer. J Clin Oncol. 2005;23:6126-31. PubMed PMID: 16135478.
  13. Bednarz B, Athar B, Xu XG. A comparative study on the risk of second primary cancers in out-of-field organs associated with radiotherapy of localized prostate carcinoma using Monte Carlo-based accelerator and patient models. Med Phys. 2010;37:1987-94. PubMed PMID: 20527532. PubMed PMCID: 2862056.
  14. Dong C, He M, Ren R, Xie Y, Yuan D, Dang B, et al. Role of the MAPK pathway in the observed bystander effect in lymphocytes co-cultured with macrophages irradiated with gamma-rays or carbon ions. Life Sci. 2015;127:19-25. PubMed PMID: 25748424.
  15. Buonanno M, de Toledo SM, Pain D, Azzam EI. Long-term consequences of radiation-induced bystander effects depend on radiation quality and dose and correlate with oxidative stress. Radiat Res. 2011;175:405-15. PubMed PMID: 21319986. PubMed PMCID: 3106980.
  16. Autsavapromporn N, Suzuki M, Funayama T, Usami N, Plante I, Yokota Y, et al. Gap junction communication and the propagation of bystander effects induced by microbeam irradiation in human fibroblast cultures: the impact of radiation quality. Radiat Res. 2013;180:367-75. PubMed PMID: 23987132. PubMed PMCID: 4058832.
  17. Anzenberg V, Chandiramani S, Coderre JA. LET-dependent bystander effects caused by irradiation of human prostate carcinoma cells with X rays or alpha particles. Radiat Res. 2008;170:467-76. PubMed PMID: 19024654. PubMed PMCID: 4132631.
  18. Autsavapromporn N, Plante I, Liu C, Konishi T, Usami N, Funayama T, et al. Genetic changes in progeny of bystander human fibroblasts after microbeam irradiation with X-rays, protons or carbon ions: the relevance to cancer risk. Int J Radiat Biol. 2015;91:62-70. PubMed PMID: 25084840.
  19. Chen HH, Jia RF, Yu L, Zhao MJ, Shao CL, Cheng WY. Bystander effects induced by continuous low-dose-rate 125I seeds potentiate the killing action of irradiation on human lung cancer cells in vitro. Int J Radiat Oncol Biol Phys. 2008;72:1560-6. PubMed PMID: 19028278.
  20. Liu Z, Mothersill CE, McNeill FE, Lyng FM, Byun SH, Seymour CB, et al. A dose threshold for a medium transfer bystander effect for a human skin cell line. Radiat Res. 2006;166:19-23. PubMed PMID: 16808607.
  21. Gow MD, Seymour CB, Byun SH, Mothersill CE. Effect of dose rate on the radiation-induced bystander response. Phys Med Biol. 2008;53:119-32. PubMed PMID: 18182691.
  22. Mothersill C, Seymour CB. Bystander and delayed effects after fractionated radiation exposure. Radiat Res. 2002;158:626-33.[0626:BADEAF]2.0.CO;2. PubMed PMID: 12385640.
  23. Soleymanifard S, Toossi MT, Samani RK, Mohebbi S. Investigation of the bystander effect in MRC5 cells after acute and fractionated irradiation in vitro. J Med Phys. 2014;39:93-7. PubMed PMID: 24872606. PubMed PMCID: 4035621.
  24. Soleymanifard S, Bahreyni Toossi MT, Kamran Samani R, Mohebbi S. Comparison of Radiation-Induced Bystander Effect in QU-DB Cells after Acute and Fractionated Irradiation: An In Vitro Study. Cell J. 2016;18:346-52. PubMed PMID: 27602316. PubMed PMCID: 5011322.
  25. Ilnytskyy Y, Koturbash I, Kovalchuk O. Radiation-induced bystander effects in vivo are epigenetically regulated in a tissue-specific manner. Environ Mol Mutagen. 2009;50:105-13. PubMed PMID: 19107897.
  26. Yahyapour R, Amini P, Rezapour S, Cheki M, Rezaeyan A, Farhood B, et al. Radiation-induced inflammation and autoimmune diseases. Mil Med Res. 2018;5(1):9.
  27. Guizard AV, Boutou O, Pottier D, Troussard X, Pheby D, Launoy G, et al. The incidence of childhood leukaemia around the La Hague nuclear waste reprocessing plant (France): a survey for the years 1978-1998. J Epidemiol Community Health. 2001;55:469-74. PubMed PMID: 11413175. PubMed PMCID: 1731936.
  28. Yoshida K, Nemoto K, Nishimura M, Seki M. Exacerbating factors of radiation-induced myeloid leukemogenesis. Leuk Res. 1993;17:437-40. PubMed PMID: 8501971.
  29. Kovalchuk O, Burke P, Besplug J, Slovack M, Filkowski J, Pogribny I. Methylation changes in muscle and liver tissues of male and female mice exposed to acute and chronic low-dose X-ray-irradiation. Mutat Res. 2004;548:75-84. PubMed PMID: 15063138.
  30. Koturbash I, Zemp F, Kolb B, Kovalchuk O. Sex-specific radiation-induced microRNAome responses in the hippocampus, cerebellum and frontal cortex in a mouse model. Mutat Res. 2011;722:114-8. PubMed PMID: 20478395.
  31. Koturbash I, Kutanzi K, Hendrickson K, Rodriguez-Juarez R, Kogosov D, Kovalchuk O. Radiation-induced bystander effects in vivo are sex specific. Mutat Res. 2008;642:28-36. PubMed PMID: 18508093.
  32. Koturbash I, Zemp FJ, Kutanzi K, Luzhna L, Loree J, Kolb B, et al. Sex-specific microRNAome deregulation in the shielded bystander spleen of cranially exposed mice. Cell Cycle. 2008;7:1658-67. PubMed PMID: 18560276.
  33. Chai Y, Calaf GM, Zhou H, Ghandhi SA, Elliston CD, Wen G, et al. Radiation induced COX-2 expression and mutagenesis at non-targeted lung tissues of gpt delta transgenic mice. Br J Cancer. 2013;108(1):91-8. PubMed PMID: 23321513. PubMed PMCID: 3553512.
  34. Fardid R, Najafi M, Salajegheh A, Kazemi E, Rezaeyan A. Radiation-induced non-targeted effect in vivo: Evaluation of cyclooygenase-2 and endothelin-1 gene expression in rat heart tissues. J Cancer Res Ther. 2017;13:51-5. PubMed PMID: 28508833.
  35. Friedman DL, Whitton J, Leisenring W, Mertens AC, Hammond S, Stovall M, et al. Subsequent neoplasms in 5-year survivors of childhood cancer: the Childhood Cancer Survivor Study. J Natl Cancer Inst. 2010;102:1083-95. PubMed PMID: 20634481. PubMed PMCID: 2907408.
  36. Armstrong GT, Sklar CA, Hudson MM, Robison LL. Long-term health status among survivors of childhood cancer: does sex matter? J Clin Oncol. 2007;25:4477-89. PubMed PMID: 17906209.
  37. Taddei PJ, Mahajan A, Mirkovic D, Zhang R, Giebeler A, Kornguth D, et al. Predicted risks of second malignant neoplasm incidence and mortality due to secondary neutrons in a girl and boy receiving proton craniospinal irradiation. Phys Med Biol. 2010;55:7067-80. PubMed PMID: 21076189. PubMed PMCID: 3001324.
  38. Valentin J. The 2007 recommendations of the international commission on radiological protection. Oxford: Elsevier; 2007.
  39. Toossi MT, Mohebbi S, Samani RK, Soleymanifard S. MRC5 and QU-DB bystander cells can produce bystander factors and induce radiation bystander effect. J Med Phys. 2014;39:192-6. PubMed PMID: 25190998. PubMed PMCID: 4154187.
  40. Soleymanifard S, Bahreyni Toossi MT, Sazgarnia A, Mohebbi S. The role of target and bystander cells in dose-response relationship of radiation-induced bystander effects in two cell lines. Iran J Basic Med Sci. 2013;16:177-83. PubMed PMID: 24298387. PubMed PMCID: 3843862.
  41. Soleymanifard S, Bahreyni MT. Comparing the level of bystander effect in a couple of tumor and normal cell lines. J Med Phys. 2012;37:102-6. PubMed PMID: 22557800. PubMed PMCID: 3339141.
  42. Cheki M, Yahyapour R, Farhood B, Rezaeyan A, Shabeeb D, Amini P, et al. COX-2 in Radiotherapy: A Potential Target for Radioprotection and Radiosensitization. Curr Mol Pharmacol. 2018;11:173–83. doi: 10.2174/1874467211666180219102520.
  43. Chai Y, Lam RK, Calaf GM, Zhou H, Amundson S, Hei TK. Radiation-induced non-targeted response in vivo: role of the TGFbeta-TGFBR1-COX-2 signalling pathway. Br J Cancer. 2013;108:1106-12. PubMed PMID: 23412109. PubMed PMCID: 3619070.
  44. Bishayee A, Hill HZ, Stein D, Rao DV, Howell RW. Free radical-initiated and gap junction-mediated bystander effect due to nonuniform distribution of incorporated radioactivity in a three-dimensional tissue culture model. Radiat Res. 2001;155:335-44.[0335:FRIAGJ]2.0.CO;2. PubMed PMID: 11175669. PubMed PMCID: 3495610.
  45. Yakovlev VA. Role of nitric oxide in the radiation-induced bystander effect. Redox Biol. 2015;6:396-400. PubMed PMID: 26355395. PubMed PMCID: 4572387.
  46. Najafi M, Fardid R, Takhshid MA, Mosleh-Shirazi MA, Rezaeyan AH, Salajegheh A. Radiation-Induced Oxidative Stress at Out-of-Field Lung Tissues after Pelvis Irradiation in Rats. Cell J. 2016;18:340-5. PubMed PMID: 27602315. PubMed PMCID: 5011321.
  47. Najafi M, Shirazi A, Motevaseli E, Geraily G, Norouzi F, Heidari M, et al. The melatonin immunomodulatory actions in radiotherapy. Biophys Rev. 2017;9:139-48. PubMed PMID: 28510090. PubMed PMCID: 5425818.
  48. Fardid R, Salajegheh A, Mosleh-Shirazi MA, Sharifzadeh S, Okhovat MA, Najafi M, et al. Melatonin Ameliorates The Production of COX-2, iNOS, and The Formation of 8-OHdG in Non-Targeted Lung Tissue after Pelvic Irradiation. Cell J. 2017;19:324-31. PubMed PMID: 28670525. PubMed PMCID: 5412791.
  49. Yahyapour R, Motevaseli E, Rezaeyan A, Abdollahi H, Farhood B, Cheki M, et al. Mechanisms of Radiation Bystander and Non-Targeted Effects: Implications to Radiation Carcinogenesis and Radiotherapy. Curr Radiopharm. 2018;11:34–45. doi: 10.2174/18744710116661712291231300.
  50. Rajendran S, Harrison SH, Thomas RA, Tucker JD. The role of mitochondria in the radiation-induced bystander effect in human lymphoblastoid cells. Radiat Res. 2011;175:159-71. PubMed PMID: 21268709.
  51. Yang G, Wu L, Chen S, Zhu L, Huang P, Tong L, et al. Mitochondrial dysfunction resulting from loss of cytochrome c impairs radiation-induced bystander effect. Br J Cancer. 2009;100:1912-6. PubMed PMID: 19455142. PubMed PMCID: 2714242.
  52. Haddadi GH, Rezaeyan A, Mosleh-Shirazi MA, Hosseinzadeh M, Fardid R, Najafi M, et al. Hesperidin as Radioprotector against Radiation-induced Lung Damage in Rat: A Histopathological Study. J Med Phys. 2017;42:25-32. PubMed PMID: 28405105. PubMed PMCID: 5370335.
  53. Rezaeyan A, Haddadi GH, Hosseinzadeh M, Moradi M, Najafi M. Radioprotective effects of hesperidin on oxidative damages and histopathological changes induced by X-irradiation in rats heart tissue. J Med Phys. 2016;41:182-91. PubMed PMID: 27651565. PubMed PMCID: 5019037.
  54. Irshad M, Chaudhuri PS. Oxidant-antioxidant system: role and significance in human body. Indian J Exp Biol. 2002;40:1233-9. PubMed PMID: 13677624.
  55. Xu S, Ding N, Pei H, Hu W, Wei W, Zhang X, et al. MiR-21 is involved in radiation-induced bystander effects. RNA Biol. 2014;11:1161-70. PubMed PMID: 25483031. PubMed PMCID: 4615763.
  56. Tian W, Yin X, Wang L, Wang J, Zhu W, Cao J, et al. The key role of miR-21-regulated SOD2 in the medium-mediated bystander responses in human fibroblasts induced by alpha-irradiated keratinocytes. Mutat Res. 2015;780:77-85. PubMed PMID: 26302379.
  57. Jiang Y, Chen X, Tian W, Yin X, Wang J, Yang H. The role of TGF-beta1-miR-21-ROS pathway in bystander responses induced by irradiated non-small-cell lung cancer cells. Br J Cancer. 2014;111:772-80. PubMed PMID: 24992582. PubMed PMCID: 4134503.
  58. Hu W, Xu S, Yao B, Hong M, Wu X, Pei H, et al. MiR-663 inhibits radiation-induced bystander effects by targeting TGFB1 in a feedback mode. RNA Biol. 2014;11:1189-98. PubMed PMID: 25483041. PubMed PMCID: 4615905.
  59. Benetti R, Gonzalo S, Jaco I, Munoz P, Gonzalez S, Schoeftner S, et al. A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferases. Nat Struct Mol Biol. 2008;15:268-79. PubMed PMID: 18311151. PubMed PMCID: 2990406.
  60. Das PM, Singal R. DNA methylation and cancer. J Clin Oncol. 2004;22:4632-42. PubMed PMID: 15542813.
  61. Hwang HW, Mendell JT. MicroRNAs in cell proliferation, cell death, and tumorigenesis. Br J Cancer. 2006;94:776-80. PubMed PMID: 16495913. PubMed PMCID: 2361377.
  62. Sedelnikova OA, Nakamura A, Kovalchuk O, Koturbash I, Mitchell SA, Marino SA, et al. DNA double-strand breaks form in bystander cells after microbeam irradiation of three-dimensional human tissue models. Cancer Res. 2007;67:4295-302. PubMed PMID: 17483342.
  63. Koturbash I, Boyko A, Rodriguez-Juarez R, McDonald RJ, Tryndyak VP, Kovalchuk I, et al. Role of epigenetic effectors in maintenance of the long-term persistent bystander effect in spleen in vivo. Carcinogenesis. 2007;28:1831-8. PubMed PMID: 17347136.
  64. Najafi M, Cheki M, Rezapoor S, Geraily G, Motevaseli E, Carnovale C, Clementi E. Metformin: Prevention of genomic instability and cancer: A review. Mutat Res . 2018;827:1–8. doi: 10.1016/j.mrgentox.2018.01.007.
  65. Ferguson LR, Chen H, Collins AR, Connell M, Damia G, Dasgupta S, et al. Genomic instability in human cancer: Molecular insights and opportunities for therapeutic attack and prevention through diet and nutrition. Semin Cancer Biol. 2015;35:S5-s24. PubMed PMID: 25869442. PubMed PMCID: 4600419.
  66. Najafi M, Shirazi A, Motevaseli E, Rezaeyan A, Salajegheh A, Rezapoor S. Melatonin as an anti-inflammatory agent in radiotherapy. Inflammopharmacology. 2017;25:403–13. doi: 10.1007/s10787-017-0332-5.
  67. Chatterjee A, Dasgupta S, Sidransky D. Mitochondrial subversion in cancer. Cancer Prev Res (Phila). 2011;4:638-54. PubMed PMID: 21543342. PubMed PMCID: 3298745.
  68. Yahyapour R, Amini P, Rezapoor S, Rezaeyan A, Farhood B, Cheki M, Fallah H. Targeting of Inflammation for Radiation Protection and Mitigation. Curr Mol Pharmacol. 2018;11:203–10. doi: 10.2174/1874467210666171108165641.
  69. Konki M, Pasumarthy K, Malonzo M, Sainio A, Valensisi C, Soderstrom M, et al. Epigenetic Silencing of the Key Antioxidant Enzyme Catalase in Karyotypically Abnormal Human Pluripotent Stem Cells. Sci Rep. 2016;6:22190. PubMed PMID: 26911679. PubMed PMCID: 4766493.
  70. Rooney S, Alt FW, Lombard D, Whitlow S, Eckersdorff M, Fleming J, et al. Defective DNA repair and increased genomic instability in Artemis-deficient murine cells. J Exp Med. 2003;197:553-65. PubMed PMID: 12615897. PubMed PMCID: 2193825.
  71. Lorimore SA, Coates PJ, Wright EG. Radiation-induced genomic instability and bystander effects: inter-related nontargeted effects of exposure to ionizing radiation. Oncogene. 2003;22:7058-69. PubMed PMID: 14557811.
  72. Morgan WF, Day JP, Kaplan MI, McGhee EM, Limoli CL. Genomic instability induced by ionizing radiation. Radiat Res. 1996;146:247-58. PubMed PMID: 8752302.
  73. Lorimore SA, Kadhim MA, Pocock DA, Papworth D, Stevens DL, Goodhead DT, et al. Chromosomal instability in the descendants of unirradiated surviving cells after alpha-particle irradiation. Proc Natl Acad Sci U S A. 1998;95:5730-3. PubMed PMID: 9576952. PubMed PMCID: 20447.
  74. Seymour CB, Mothersill C. Delayed expression of lethal mutations and genomic instability in the progeny of human epithelial cells that survived in a bystander-killing environment. Radiat Oncol Investig. 1997;5:106-10.;2-1. PubMed PMID: 9303065.
  75. Little JB, Nagasawa H, Pfenning T, Vetrovs H. Radiation-induced genomic instability: delayed mutagenic and cytogenetic effects of X rays and alpha particles. Radiat Res. 1997;148:299-307. PubMed PMID: 9339945.
  76. Lyng FM, Seymour CB, Mothersill C. Initiation of apoptosis in cells exposed to medium from the progeny of irradiated cells: a possible mechanism for bystander-induced genomic instability? Radiat Res. 2002;157:365-70.[0365:IOAICE]2.0.CO;2. PubMed PMID: 11893237.
  77. Hall EJ, Hei TK. Genomic instability and bystander effects induced by high-LET radiation. Oncogene. 2003;22:7034-42. PubMed PMID: 14557808.
  78. Niwa O. Induced genomic instability in irradiated germ cells and in the offspring; reconciling discrepancies among the human and animal studies. Oncogene. 2003;22:7078-86. PubMed PMID: 14557813.
  79. Salimi M, Mozdarani H, Nazari E. Cytogenetic Alterations in Preimplantation Mice Embryos Following Male Mouse Gonadal Gamma-irradiation: Comparison of Two Methods for Reproductive Toxicity Screening. Avicenna J Med Biotechnol. 2014;6:130-9. PubMed PMID: 25215176. PubMed PMCID: 4147099.
  80. Filkowski JN, Ilnytskyy Y, Tamminga J, Koturbash I, Golubov A, Bagnyukova T, et al. Hypomethylation and genome instability in the germline of exposed parents and their progeny is associated with altered miRNA expression. Carcinogenesis. 2010;31:1110-5. PubMed PMID: 19959559.
  81. Koturbash I, Baker M, Loree J, Kutanzi K, Hudson D, Pogribny I, et al. Epigenetic dysregulation underlies radiation-induced transgenerational genome instability in vivo. Int J Radiat Oncol Biol Phys. 2006;66:327-30. PubMed PMID: 16965987.
  82. Tamminga J, Kovalchuk O. Role of DNA damage and epigenetic DNA methylation changes in radiation-induced genomic instability and bystander effects in germline in vivo. Curr Mol Pharmacol. 2011;4:115-25. PubMed PMID: 21143184.
  83. Tamminga J, Kathiria P, Koturbash I, Kovalchuk O. DNA damage-induced upregulation of miR-709 in the germline downregulates BORIS to counteract aberrant DNA hypomethylation. Cell Cycle. 2008;7:3731-6. PubMed PMID: 19029807.
  84. Tamminga J, Koturbash I, Baker M, Kutanzi K, Kathiria P, Pogribny IP, et al. Paternal cranial irradiation induces distant bystander DNA damage in the germline and leads to epigenetic alterations in the offspring. Cell Cycle. 2008;7:1238-45. PubMed PMID: 18418050.
  85. Luke GA, Riches AC, Bryant PE. Genomic instability in haematopoietic cells of F1 generation mice of irradiated male parents. Mutagenesis. 1997;12:147-52. PubMed PMID: 9175639.
  86. Lord BI. Transgenerational susceptibility to leukaemia induction resulting from preconception, paternal irradiation. Int J Radiat Biol. 1999;75:801-10. PubMed PMID: 10489891.
  87. Gardner MJ. Leukemia in children and paternal radiation exposure at the Sellafield nuclear site. J Natl Cancer Inst Monogr. 1992;(12):133-5. PubMed PMID: 1616797.
  88. Najafi M, Salajegheh A, Rezaeyan A. Bystander Effect and Second Primary Cancers following Radiotherapy: What are its Significances? J Med Phys. 2017;42:55-6. PubMed PMID: 28405109. PubMed PMCID: 5370339.