Medical Radiology and Radiation Safety. 2022. Vol. 67. № 4

Transmission of Radiation-Induced Genome Instability
from Irradiated Parents to their Offspring

D.S. Oslina, V.L. Rybkina, T.V. Azizova

Southern Urals Biophysics Institute, Ozyorsk, Chelyabinsk region, Russia

Contact person: Oslina Darja Sergeevna, e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it. , This email address is being protected from spambots. You need JavaScript enabled to view it.

Abstract

Numerous studies allow to suppose a transmission of radiation-induced genome instability from irradiated parents to their offspring on cell, chromosome and molecular genetic level. This review focuses on transmission of radiation-induced genome instability from irradiated parents to their offspring. Data of genome instability in animal experiments and in offspring of occupationally exposed human or human exposed in a radiation accident, and in offspring of parents exposed to radiotherapy are reviewed. The possible mechanisms of lineage transmission of genome instability are discussed. High dose irradiation can lead to DNA damage, changes in methylation patterns and miRNAs expression in parents and their offspring and result in mutations, chromosome aberration and destabilization of genome. Non-coding RNAs (miRNA, piRNA, nsRNA) are supposed to contribute to transgenerational effects, since they can target genes, change chromatin structure and disregulate gene expression.

Keywords: ionizing radiation, transgenerational effects, genetic effects, epigenetic effects

For citation: Oslina DS, Rybkina VL, Azizova TV. Transmission of Radiation-Induced Genome Instability from Irradiated Parents to their Offspring. Medical Radiology and Radiation Safety. 2022;67(4):10-18. DOI: 10.33266/1024-6177-2022-67-4-10-18

References

1. Morgan WF. Is there a common mechanism underlying genomic instability, bystander effects and other nontargeted effects of exposure to ionizing radiation? Oncogene. 2003; 22: 7094–7099.

2. Morgan WF, Sowa MB. Non-targeted bystander effects induced by ionizing radiation. Mutation Research. 2007; 616: 159–164.

3. Kovalchuk I, Kovalchuk O. Genome Stability: From Virus to Human Application. Academic Press; 2016. 712 pp.

4. Dugan LC, Bedford JS. Are Chromosomal Instabilities Induced by Exposure of Cultured Normal Human Cells to Low- or High-LET Radiation? Radiat Res. 2003; 159(3): 301–311.

5. Patkin EL, Pavlinova LI, Sofronov GA. Influence of ecotoxicants on mammalian embryogenesis and gametogenesis: epigenetic mechanisms. Interdisciplinary scientific and applied journal "Biosphere". 2013; 5(4): 450–472.

6. Baverstock K. Why do we need a new paradigm in radiobiology? Mutation Research. 2010; 687: 3–6.

7. Little MP, Goodhead DT, Bridges BA, Bouffler SD. Evidence relevant to untargeted and transgenerational effects in the offspring of irradiated parents. Mutation Research. 2013; 753(1): 50–67.

8. Committee on Medical Aspects of Radiation in the Environment (COMARE). Seventh Report. Chilton, National Radiological Protection Board; 2002. Parents occupationally exposed to radiation prior to the conception of their children. A review of the evidence concerning the incidence of cancer in their children.

9. Committee on Medical Aspects of Radiation in the Environment (COMARE). Eighth Report. Chilton, National Radiological Protection Board; 2004. Review of pregnancy outcomes following preconceptional exposure to radiation.

10. Slovinská L, Elbertová A, Mišúrová E. Transmission of genome damage from irradiated male rats to their progeny. Mutation Research. 2004: 559; 29–37.

11. Mughal SK, Myazin AE, Zhavoronkov LP, Mughal SK, Myazin AE, Zhavoronkov LP, Rubanovich AV, Dubrova YE. The dose and dose-rate effects of paternal irradiation on transgenerational instability in mice: a radiotherapy connection. PLoS One. 2012; 7(7): 1−5.

12. Glen CD, Dubrova YE. Exposure to anticancer drugs can result in transgenerational genomic instability in mice. Proc Natl Acad Sci USA. 2012; 109: 2984–2988.

13. Lomaeva MG, Vasil’eva GV, Fomenko LA, Antipova VN, Gaziev AI, Bezlepkin VG. Increased Genomic Instability in Somatic Cells of the Progeny of Female Mice Exposed to Acute X−Radiation in the Preconceptional Period. Rus J Genetics. 2011; 47(10): 1221.

14. Lomaeva МG, Fomenko LA, Vasil’eva GV, Bezlepkin VG. Tissue-specific Changes in the Polymorphism of Simple Repeats in DNA of the Offspring of Different Sex Born from Irradiated Male or Female Mice. Radiation biology. Radioecology. 2016; 56(2): 149–155.

15. Nefedov IY, Nefedova IY, Palyga GF. Actual aspects of the problem of the genetic consequences of mammalian exposure. Radiation biology. Radioecology. 2000; 40(4); 358–372.

16. Abouzeid AHE, Barber RC, Dubrova YE. The effects of maternal irradiation during adulthood on mutation induction and transgenerational instability in mice. Mutation Research. 2012; 732: 21–25.

17. Somers CM. Expanded simple tandem repeat (ESTR) mutation induction in the male germline: lessons learned from lab mice. Mutation Research. 2006; 598: 35–49.

18. Barber RC, Hickenbotham P, Hatch T, Kelly D, Topchiy N, Almeida GM, Jones GD, Johnson GE, Parry JM, Rothkamm K, Dubrova YE. Radiation-induced transgenerational alterations in genome stability and DNA damage. Oncogene. 2006; 25: 7336–7342.

19. Min H, Sung M, Son M, Kawasaki I, Shim YH. Transgenerational effects of proton beam irradiation on Caenorhabditis elegans germline apoptosis. Biochemical and Biophysical Research Communications. 2017; 490(3): 608–615.

20. Parisot F, Bourdineaud JP, Plaire D, Adam-Guillermin C, Alonzo F. DNA alterations and effects on growth and reproduction in Daphnia magna during chronic exposure to gamma radiation over three successive generations. Aquatic Toxicology. 2015; 163: 27–36.

21. Sarapultseva EI, Dubrova YE. The long-term effects of acute exposure to ionising radiation on survival and fertility in Daphnia magna. Environmental Research. 2016; 150: 138–143.

22. Smith RW, Seymour CB, Moccia RD, Mothersill CE. Irradiation of rainbow trout at early life stages results in trans-generational effects including the induction of a bystander effect in non-irradiated fish. Environmental Research. 2016; 145: 26–38. 

23. Shimada Atsuko, Shima Akihiro. Transgenerational genomic instability as revealed by a somatic mutation assay using the medaka fish. Mutation Research. 2004; 552: 119–124. 

24. Tsyusko O, Glenn T, Yi Y, Joice G, Jones K, Aizawa K, Coughlin D, Zimbrick J, Hinton T. Differential genetic responses to ionizing irradiation in individual families of Japanese medaka. Mutation Research. 2011; 718: 18–23.

25. Hurem S, Gomes T, Brede DA, Lindbo Hansen E, Mutoloki S, Fernandez C, Mothersill C, Salbu B, Kassaye YA, Olsen AK, Oughton D, Aleström P, Lyche JL. Parental gamma irradiation induces reprotoxic effects accompanied by genomic instability in zebrafish (Danio rerio) embryos. Environmental Research. 2017; 159: 564–578.

26. Hurem S, Martín LM, Lindeman L, Brede DA, Salbu B, Lyche JL, Aleström P, Kamstra JH. Parental exposure to gamma radiation causes progressively altered transcriptomes linked to adverse effects in zebrafish offspring. Environmental Pollution. 2018; 234: 855–863.

27. Gardner MJ, Snee MP, Hall AJ, Powell CA, Downes S, Terrell JD. Results of case-control study of leukaemia and lymphoma among young people near Sellafield nuclear plant in West Cumbria. BMJ. 1990; 300: 423–429.

28. Dubrova YE, Bersimbaev RI, Djansugurova LB, Tankimanova MK, Mamyrbaeva ZZh, Mustonen R, Lindholm C, Hultén M, Salomaa S. Nuclear weapons tests and human germline mutation rate. Science. 2002; 295: 1037.

29. Livshits LA, Malyarchuk SG, Kravchenko SA, Lukyanova EM, Antipkin YG, Arabskaya LP, Matsuka GH, Petit E, Giraudeau F, Gourmelon P, Vergnaud G, Le Guen B. Children of Chernobyl cleanup workers do not show elevated rates of mutations in minisatellite alleles. Radiation Research. 2001; 155: 74–80.

30. Furitsu K, Ryo H, Yeliseeva KG, Thuy le TT, Kawabata H, Krupnova EV, Trusova VD, Rzheutsky VA, Nakajima H, Kartel N, Nomura T. Microsatellite mutations show no increases in the children of the Chernobyl liquidators. Mutation Research. 2005; 581: 69–82.

31. Kiuru A, Auvinen A, Luokkamaki M, Makkonen K, Veidebaum T, Tekkel M, Rahu M, Hakulinen T, Servomaa K, Rytömaa T, Mustonen R. Hereditary minisatellite mutations among the offspring of Estonian Chernobyl cleanup workers. Radiation Research. 2003; 159: 651–655.

32. Kodaira M, Izumi S. Takahashi N, Nakamura N. No evidence of radiation effect on mutation rates at hypervariable minisatellite loci in the germ cells of atomic bomb survivors. Radiation Research. 2004; 162: 350–356.

33. Bezlepkin VG, Kirillova EN, Zakharova ML, Pavlova OS, Lomaeva MG, Fomenko LA, Antipova VN, Gaziev AI. Delayed and Transgenerational Molecular and Genetic Effects of Prolonged Influence of Ionizing Radiation in Nuclear Plant Workers. Radiation biology. Radioecology. 2011; 51(1); 20–32.

34. Rees GS, Trikik MZ, Winther JF, Tawn EJ, Stovall M, Olsen JH, Rechnitzer C, Schrøder H, Guldberg P, Boice JD Jr. A pilot study examining germline minisatellite mutations in the offspring of Danish childhood and adolescent cancer survivors treated with radiotherapy. Int J Radiat Biol. 2006; 82(3): 153–160.

35. Vignard J, Mirey G, Salles B. Ionizing-radiation induced DNA double-strand breaks: A direct and indirect lighting up. Radiotherapy and Oncology. 2013; 108: 362–369.

36. Tawn EJ, Whitehouse CA, Winther JF, Curwen GB, Rees GS, Stovall M, Olsen JH, Guldberg P, Rechnitzer C, Schrøder H, Boice JD Jr. Chromosome analysis in childhood cancer survivors and their offspring – no evidence for radiotherapy-induced persistent genomic instability. Mutation Research. 2005; 583: 198–206.

37. Signorello LB, Mulvihill JJ, Green DM, Munro HM, Stovall M, Weathers RE, Mertens AC, Whitton JA, Robison LL, Boice JD Jr. Stillbirth and neonatal death in relation to radiation exposure before conception: a retrospective cohort study. Lancet. 2010; 376: 624–630.

38. Kuzmina NS, Lapteva NSh, Rubanovich AV. Hypermethylation of gene promoters in peripheral blood leukocytes in humans longterm after radiation exposure. Environmental Research. 2016; 146: 10–17.

39. Suzuki R, Ojima M, Kodama S, Watanabe M. Delayed activation of DNA damage checkpoint and radiation-induced genomic instability. Mutat Res. 2006; 597 (1–2): 73–77.

40. Venkatesan S, Natarajan AT, Hande M. Chromosomal instability—mechanisms and consequences. Mutation Research. 2015; 793: 176–184.

41. Sabatier L, Ricoul M, Pottier G, Murnane JP. The loss of single telomere can result in instability of multiple chromosomes in a human tumor cell line. Mol Cancer Res. 2005; 3: 139–150.

42. Blake GET, Watson ED. Unravelling the complex mechanisms of transgenerational epigenetic inheritance. Current Opinion in Chemical Biology. 2016; 33: 101–107.

43. Molla-Herman A, Matias NR, Huynh JR. Chromatin modifications regulate germ cell development and transgenerational information relay. Current Opinion in Insect Science. 2014; 1: 10–18.

44. Pogribny I, Koturbash I, Tryndyak V, Hudson D, Stevenson SML, Sedelnikova O, Bonner W, Kovalchuk O. Fractionated low-dose radiation exposure leads to accumulation of DNA damage and profound alterations in DNA and histone methylation in the murine thymus. Mol Cancer Res. 2005; 3(10): 553–561. 

45. 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. Mutation Research. 2004; 548: 75–84.

46. Koturbash I, Boyko A, Rodriguez-Juarez R, McDonald RJ, Tryndyak VP, Kovalchuk I, Pogribny IP, Kovalchuk O. Role of epigenetic effectors in maintenance of the long-term persistent bystander effect in spleen in vivo. Carcinogenesis. 2007; 28(8): 1831–1838.

47. Transgenerational Epigenetics / ed. Tollefsbol T. Academic Press, 2014. 412 pp. http://dx.doi.org/10.1016/B978-0-12-405944-3.00011-8.

48. Niwa O. Indirect mechanisms of radiation induced genomic instability at repeat loci // International Congress Series. 2007; 1299: 135–145. 

49. Scully R, Xie A. Double strand break repair functions of histone H2AX. Mutation Research. Fundamental and Molecular Mechanisms of Mutagenesis. 2013; 750 (1–2):5–14.

50. Vasilyev S, Velichevskaya AI, Vishnevskaya TV, Belenko AA, Gribova O, Plaksin MB, Startseva ZhA, Lebedev I. Background Level of γH2AX Foci in Human Cells as a Factor of Individual Radiosensitivity. Radiation biology. Radioecology. 2015; 55(4): 402–410.

51. Merrifield M, Kovalchuk O. Sins of Fathers Through a Scientific Lens: Transgenerational Effects Genome Stability. http://dx.doi.org/10.1016/B978-0-12-803309-8.00034-3

52. Ahmad P, Sana J, Slavik M, Slampa P, Smilek P, Slaby O. MicroRNAs Involvement in Radioresistance of Head and Neck Cancer. Disease Markers. 2017. Article ID 8245345. http://dx.doi.org/10.1155/2017/8245345

53. Ilnytskyy Y, Zemp FJ, Koturbash I, Kovalchuk O. Altered microRNA expression patterns in irradiated hematopoietic tissues suggest a sex-specific protective mechanism. Biochemical and Biophysical Research Communications. 2008; 377: 41–45.

54. Barber RC, Dubrova YE, Gant TW. Radiation-induced transgenerational alterations in MicroRNA expression. Toxicology. 2011; 290: 1–46.

55. Filkowski JN, Ilnytskyy Y, Tamminga J, Koturbash I, Golubov A, Bagnyukova T, Pogribny IP, Kovalchuk O. Hypomethylation and genome instability in the germline of exposed parents and their progeny is associated with altered miRNA expression. Carcinogenesis. 2010; 6: 1110–1115.

56. Aravin AA, Sachidanandam R, Bourc’his D, Schaefer C, Pezic D, Fejes Toth K, Bestor T, Hannon GJ. A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol Cell. 2008; 31(6): 785–799.

57. Thomson T, Lin H. The biogenesis and function of PIWI proteins and piRNAs: progress and prospect. Annu Rev Cell Dev Biol. 2009; 25: 355–376.

58. Rechavi O, Houri-Ze’evi L, Anava S, Goh WSS, Kerk SY, Hannon GJ, Hobert O. Starvation-Induced Transgenerational Inheritance of Small RNAs in C. elegans. Cell. 2014; 158: 277–287. 

59. Nelson VR Nadeau JH. Transgenerational genetic effects. Epigenomics. 2010; 2(6):797–806.

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Conflict of interest. The authors declare no conflict of interest.

Financing. The study had no sponsorship.

Contribution. Article was prepared with equal participation of the authors.

Article received: 15.03.2022.  Accepted for publication: 11.05.2022