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2012 | OriginalPaper | Buchkapitel

6. Role of Epigenetic Changes in Radiation-Induced Genome Instability

verfasst von : Slava Ilnytskyy, Jody Filkowski, Olga Kovalchuk

Erschienen in: Radiobiology and Environmental Security

Verlag: Springer Netherlands

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Abstract

Ionizing radiation (IR) is an important diagnostic and treatment modality, yet it is also a potent genotoxic agent that causes genome instability and carcinogenesis. While modern cancer radiation therapy has led to increased patient survival rates, the risk of radiation treatment-related complications is becoming a growing problem as radiation poses a threat to the exposed individuals and their progeny. Radiation-induced genome instability, which manifests as an elevated mutation rate (both delayed and non-targeted), chromosomal aberrations and changes in gene expression, has been well-documented in directly exposed cells and organisms. However, it has also been observed in distant, naïve, out-of-field, ‘bystander’ cells and their progeny. Enigmatically, this increased instability is even observed in the pre-conceptually exposed progeny of animals, including humans. The mechanisms by which these distal effects arise remain obscure and, recently, have been proposed to be epigenetic in nature.

Epigenetic alterations which comprise mitotically and meiotically heritable changes in gene expression that are not caused by changes in the primary DNA sequence, are increasingly being recognized for their roles in health and disease. Three major areas of epigenetics—DNA methylation, histone modifications and small RNA-mediated silencing, are known to have profound effects on controlling gene expression. Yet, the exact nature of the epigenetic changes and their precise roles in IR responses and IR-induced genome instability still need to be delineated. Here we will focus on the nature of epigenetic changes in directly exposed and bystander tissues. We will also discuss the emerging evidence that support the role of epigenetic deregulation in transgenerational effects.

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Vorheriges Kapitel Implications for Human and Environmental Health of Low Doses of Radiation

Nächstes Kapitel Radiation and Terror

Akleev AV, Dubrova Iu E et al (2007) The effects of chronic radiation exposure on the frequency of mutations at minisatellite DNA loci in residents of the Techa Riverside Villages. Radiats Biol Radioecol 47(5):558–566

Amundson SA, Fornace AJ Jr (2003) Monitoring human radiation exposure by gene expression profiling: possibilities and pitfalls. Health Phys 85(1):36–42CrossRef

Amundson SA, Lee RA et al (2003) Differential responses of stress genes to low dose-rate gamma irradiation. Mol Cancer Res 1(6):445–452

Andreev SG, Eidelman YA et al (2006) Mechanistic modelling of genetic and epigenetic events in radiation carcinogenesis. Radiat Prot Dosimetry 122(1–4):335–339

Aravin AA, Sachidanandam R et al (2007) Developmentally regulated piRNA clusters implicate MILI in transposon control. Science 316(5825):744–747CrossRef

Aravin AA, Sachidanandam R et al (2008) A piRNA pathway primed by individual transposons is linked to de novo DNA methylation in mice. Mol Cell 31(6):785–799CrossRef

Barber R, Plumb MA et al (2002) Elevated mutation rates in the germ line of first- and second-generation offspring of irradiated male mice. Proc Natl Acad Sci USA 99(10):6877–6882CrossRef

Baylin SB, Chen WY (2005) Aberrant gene silencing in tumor progression: implications for control of cancer. Cold Spring Harb Symp Quant Biol 70:427–433CrossRef

Baylin SB, Ohm JE (2006) Epigenetic gene silencing in cancer–a mechanism for early oncogenic pathway addiction? Nat Rev Cancer 6(2):107–116CrossRef

10.

Bernstein E, Allis CD (2005) RNA meets chromatin. Genes Dev 19(14):1635–1655CrossRef

11.

Bird A (2007) Perceptions of epigenetics. Nature 447(7143):396–398CrossRef

12.

Brykczynska U, Hisano M et al (2010) Repressive and active histone methylation mark distinct promoters in human and mouse spermatozoa. Nat Struct Mol Biol 17(6):679–687CrossRef

13.

Carls N, Schiestl RH (1999) Effect of ionizing radiation on transgenerational appearance of p(un) reversions in mice. Carcinogenesis 20(12):2351–2354CrossRef

14.

Carmell MA, Girard A et al (2007) MIWI2 is essential for spermatogenesis and repression of transposons in the mouse male germline. Dev Cell 12(4):503–514CrossRef

15.

Celeste A, Difilippantonio S et al (2003) H2AX haploinsufficiency modifies genomic stability and tumor susceptibility. Cell 114(3):371–383CrossRef

16.

Celeste A, Fernandez-Capetillo O et al (2003) Histone H2AX phosphorylation is dispensable for the initial recognition of DNA breaks. Nat Cell Biol 5(7):675–679CrossRef

17.

Chauveinc L, Giraud P et al (1998) Radiotherapy-induced solid tumors: review of the literature and risk assessment. Cancer Radiother 2(1):12–18

18.

Cheung P, Lau P (2005) Epigenetic regulation by histone methylation and histone variants. Mol Endocrinol 19(3):563–573CrossRef

19.

Criswell T, Leskov K et al (2003) Transcription factors activated in mammalian cells after clinically relevant doses of ionizing radiation. Oncogene 22(37):5813–5827CrossRef

20.

Daher A, Varin M et al (1998) Effect of pre-conceptional external or internal irradiation of N5 male mice and the risk of leukemia in their offspring. Carcinogenesis 19(9):1553–1558CrossRef

21.

Das PP, Bagijn MP et al (2008) Piwi and piRNAs act upstream of an endogenous siRNA pathway to suppress Tc3 transposon mobility in the Caenorhabditis elegans germline. Mol Cell 31(1):79–90CrossRef

22.

Draper GJ (1989) General overview of studies of multigeneration carcinogenesis in man, particularly in relation to exposure to chemicals. IARC Sci Publ 96:275–288

23.

Dubrova YE, Jeffreys AJ et al (1993) Mouse minisatellite mutations induced by ionizing radiation. Nat Genet 5(1):92–94CrossRef

24.

Dubrova YE, Nesterov VN et al (1996) Human minisatellite mutation rate after the Chernobyl accident. Nature 380(6576):683–686CrossRef

25.

Dubrova YE, Nesterov VN et al (1997) Further evidence for elevated human minisatellite mutation rate in Belarus eight years after the Chernobyl accident. Mutat Res 381(2):267–278CrossRef

26.

Dubrova YE, Plumb M et al (1998) Stage specificity, dose response, and doubling dose for mouse minisatellite germ-line mutation induced by acute radiation. Proc Natl Acad Sci USA 95(11):6251–6255CrossRef

27.

Dubrova YE, Plumb M et al (2000) Transgenerational mutation by radiation. Nature 405(6782):37CrossRef

28.

Dubrova YE, Bersimbaev RI et al (2002) Nuclear weapons tests and human germline mutation rate. Science 295(5557):1037CrossRef

29.

Dubrova YE, Ploshchanskaya OG et al (2006) Minisatellite germline mutation rate in the Techa River population. Mutat Res 602(1–2):74–82

30.

Fabbri M, Ivan M et al (2007) Regulatory mechanisms of microRNAs involvement in cancer. Expert Opin Biol Ther 7(7):1009–1019CrossRef

31.

Fan YJ, Wang Z et al (1995) Dose-response of a radiation induction of a germline mutation at a hypervariable mouse minisatellite locus. Int J Radiat Biol 68(2):177–183CrossRef

32.

Farazi TA, Juranek SA et al (2008) The growing catalog of small RNAs and their association with distinct Argonaute/Piwi family members. Development 135(7):1201–1214CrossRef

33.

Fei P, El-Deiry WS (2003) P53 and radiation responses. Oncogene 22(37):5774–5783CrossRef

34.

Feinberg AP (2004) The epigenetics of cancer etiology. Semin Cancer Biol 14(6):427–432CrossRef

35.

Feinberg AP, Vogelstein B (1983) Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature 301(5895):89–92CrossRef

36.

Filkowski JN, Ilnytskyy Y et al (2010) Hypomethylation and genome instability in the germline of exposed parents and their progeny is associated with altered miRNA expression. Carcinogenesis 31(6):1110–1115CrossRef

37.

Fraga MF, Ballestar E et al (2005) Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nat Genet 37(4):391–400CrossRef

38.

Goldman M (1982) Ionizing radiation and its risks. West J Med 137(6):540–547

39.

Goll MG, Bestor TH (2005) Eukaryotic cytosine methyltransferases. Annu Rev Biochem 74:481–514CrossRef

40.

Grandjean V, Gounon P et al (2009) The miR-124-Sox9 paramutation: RNA-mediated epigenetic control of embryonic and adult growth. Development 136(21):3647–3655CrossRef

41.

Grewal SI, Moazed D (2003) Heterochromatin and epigenetic control of gene expression. Science 301(5634):798–802CrossRef

42.

Hajkova P, Erhardt S et al (2002) Epigenetic reprogramming in mouse primordial germ cells. Mech Dev 117(1–2):15–23CrossRef

43.

He S, Dunn KL et al (2008) Chromatin organization and nuclear microenvironments in cancer cells. J Cell Biochem 104(6):2004–2015CrossRef

44.

Holliday R (1990) DNA methylation and epigenetic inheritance. Philos Trans R Soc Lond B Biol Sci 326(1235):329–338CrossRef

45.

Huang L, Snyder AR, Morgan WF (2003) Radiation-induced genomic instability and its implications for radiation carcinogenesis. Oncogene 22:5848–5854CrossRef

46.

Hutvagner G, Zamore PD (2002) A microRNA in a multiple-turnover RNAi enzyme complex. Science 297(5589):2056–2060CrossRef

47.

Hwang HW, Mendell JT (2006) MicroRNAs in cell proliferation, cell death, and tumorigenesis. Br J Cancer 94(6):776–780CrossRef

48.

Iliakis G, Wang Y et al (2003) DNA damage checkpoint control in cells exposed to ionizing radiation. Oncogene 22(37):5834–5847CrossRef

49.

Jaenisch R, Bird A (2003) Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet 33(Suppl):245–254CrossRef

50.

Jeggo P, Lobrich M (2006) Radiation-induced DNA damage responses. Radiat Prot Dosimetry 122(1–4):124–127

51.

Jenuwein T, Allis CD (2001) Translating the histone code. Science 293(5532):1074–1080CrossRef

52.

Jirtle RL, Skinner MK (2007) Environmental epigenomics and disease susceptibility. Nat Rev Genet 8(4):253–262CrossRef

53.

Kalinich JF, Catravas GN et al (1989) The effect of gamma radiation on DNA methylation. Radiat Res 117(2):185–197CrossRef

54.

Kaup S, Grandjean V et al (2006) Radiation-induced genomic instability is associated with DNA methylation changes in cultured human keratinocytes. Mutat Res 597(1–2):87–97

55.

Klose RJ, Bird AP (2006) Genomic DNA methylation: the mark and its mediators. Trends Biochem Sci 31(2):89–97CrossRef

56.

Koturbash I, Pogribny I et al (2005) Stable loss of global DNA methylation in the radiation-target tissue–a possible mechanism contributing to radiation carcinogenesis? Biochem Biophys Res Commun 337(2):526–533CrossRef

57.

Koturbash I, Rugo RE et al (2006) Irradiation induces DNA damage and modulates epigenetic effectors in distant bystander tissue in vivo. Oncogene 25(31):4267–4275CrossRef

58.

Koturbash I, Boyko A et al (2007) Role of epigenetic effectors in maintenance of the long-term persistent bystander effect in spleen in vivo. Carcinogenesis 28(8):1831–1838CrossRef

59.

Koturbash I, Zemp FJ et al (2008) Sex-specific microRNAome deregulation in the shielded bystander spleen of cranially exposed mice. Cell Cycle 7(11):1658–1667CrossRef

60.

Kovalchuk O, Burke P et al (2004) Methylation changes in muscle and liver tissues of male and female mice exposed to acute and chronic low-dose X-ray-irradiation. Mutat Res 548(1–2):75–84

61.

Kovalchuk O, Zemp FJ et al (2010) microRNAome changes in bystander three-dimensional human tissue models suggest priming of apoptotic pathways. Carcinogenesis 31(10):1882–1888CrossRef

62.

Lane N, Dean W et al (2003) Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse. Genesis 35(2):88–93CrossRef

63.

Liang G, Chan MF et al (2002) Cooperativity between DNA methyltransferases in the maintenance methylation of repetitive elements. Mol Cell Biol 22(2):480–491CrossRef

64.

Little JB (2000) Radiation carcinogenesis. Carcinogenesis 21(3):397–404CrossRef

65.

Little MP (2003) Risks associated with ionizing radiation. Br Med Bull 68:259–275CrossRef

66.

Lord BI (1999) Transgenerational susceptibility to leukaemia induction resulting from preconception, paternal irradiation. Int J Radiat Biol 75(7):801–810CrossRef

67.

Lord BI, Woolford LB et al (1998) Tumour induction by methyl-nitroso-urea following preconceptional paternal contamination with plutonium-239. Br J Cancer 78(3):301–311CrossRef

68.

Loree J, Koturbash I et al (2006) Radiation-induced molecular changes in rat mammary tissue: possible implications for radiation-induced carcinogenesis. Int J Radiat Biol 82(11):805–815CrossRef

69.

Luke GA, Riches AC et al (1997) Genomic instability in haematopoietic cells of F1 generation mice of irradiated male parents. Mutagenesis 12(3):147–152CrossRef

70.

Luning KG, Frolen H et al (1976) Genetic effects of 239Pu salt injections in male mice. Mutat Res 34(3):539–542CrossRef

71.

Minamoto T, Mai M et al (1999) Environmental factors as regulators and effectors of multistep carcinogenesis. Carcinogenesis 20(4):519–527CrossRef

72.

Mohr U, Dasenbrock C et al (1999) Possible carcinogenic effects of X-rays in a transgenerational study with CBA mice. Carcinogenesis 20(2):325–332CrossRef

73.

Mole RH (1979) Radiation effects on pre-natal development and their radiological significance. Br J Radiol 52(614):89–101CrossRef

74.

Muegge K (2005) Lsh, a guardian of heterochromatin at repeat elements. Biochem Cell Biol 83(4):548–554CrossRef

75.

Niwa O, Fan YJ et al (1996) Induction of a germline mutation at a hypervariable mouse minisatellite locus by 252Cf radiation. J Radiat Res (Tokyo) 37(3):217–224CrossRef

76.

Nomura T (1982) Parental exposure to x rays and chemicals induces heritable tumours and anomalies in mice. Nature 296(5857):575–577CrossRef

77.

Nomura T (1983) X-ray-induced germ-line mutation leading to tumors. Its manifestation in mice given urethane post-natally. Mutat Res 121(1):59–65CrossRef

78.

Nomura T (1989) Role of radiation-induced mutations in multigeneration carcinogenesis. IARC Sci Publ 96:375–387

79.

Nomura T (2006) Transgenerational effects of radiation and chemicals in mice and humans. J Radiat Res (Tokyo) 47(Suppl B):B83–B97CrossRef

80.

Nomura T, Nakajima H et al (2004) Transgenerational transmission of radiation- and chemically induced tumors and congenital anomalies in mice: studies of their possible relationship to induced chromosomal and molecular changes. Cytogenet Genome Res 104(1–4):252–260CrossRef

81.

Okano M, Bell DW et al (1999) DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99(3):247–257CrossRef

82.

Pilch DR, Sedelnikova OA et al (2003) Characteristics of gamma-H2AX foci at DNA double-strand breaks sites. Biochem Cell Biol 81(3):123–129CrossRef

83.

Pogribny I, Raiche J et al (2004) Dose-dependence, sex- and tissue-specificity, and persistence of radiation-induced genomic DNA methylation changes. Biochem Biophys Res Commun 320(4):1253–1261CrossRef

84.

Pogribny I, Koturbash I et al (2005) 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 3(10):553–561CrossRef

85.

Powell SN, Kachnic LA (2003) Roles of BRCA1 and BRCA2 in homologous recombination, DNA replication fidelity and the cellular response to ionizing radiation. Oncogene 22(37):5784–5791CrossRef

86.

Raiche J, Rodriguez-Juarez R et al (2004) Sex- and tissue-specific expression of maintenance and de novo DNA methyltransferases upon low dose X-irradiation in mice. Biochem Biophys Res Commun 325(1):39–47CrossRef

87.

Rassoulzadegan M, Grandjean V et al (2006) RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse. Nature 441(7092):469–474CrossRef

88.

Rassoulzadegan M, Grandjean V et al (2007) Inheritance of an epigenetic change in the mouse: a new role for RNA. Biochem Soc Trans 35(Pt 3):623–625

89.

Robertson KD (2001) DNA methylation, methyltransferases, and cancer. Oncogene 20(24):3139–3155CrossRef

90.

Robertson KD (2002) DNA methylation and chromatin–unraveling the tangled web. Oncogene 21(35):5361–5379CrossRef

91.

Robertson KD, Wolffe AP (2000) DNA methylation in health and disease. Nat Rev Genet 1(1):11–19CrossRef

92.

Rodemann HP, Blaese MA (2007) Responses of normal cells to ionizing radiation. Semin Radiat Oncol 17(2):81–88CrossRef

93.

Rogakou EP, Pilch DR et al (1998) DNA double-stranded breaks induce histone H2AX phosphorylation on serine 139. J Biol Chem 273(10):5858–5868CrossRef

94.

Rountree MR, Bachman KE et al (2001) DNA methylation, chromatin inheritance, and cancer. Oncogene 20(24):3156–3165CrossRef

95.

Saha A, Wittmeyer J et al (2006) Chromatin remodelling: the industrial revolution of DNA around histones. Nat Rev Mol Cell Biol 7(6):437–447CrossRef

96.

Sanders SL, Portoso M et al (2004) Methylation of histone H4 lysine 20 controls recruitment of Crb2 to sites of DNA damage. Cell 119(5):603–614CrossRef

97.

Sedelnikova OA, Pilch DR et al (2003) Histone H2AX in DNA damage and repair. Cancer Biol Ther 2(3):233–235

98.

Sedelnikova OA, Nakamura A et al (2007) DNA double-strand breaks form in bystander cells after microbeam irradiation of three-dimensional human tissue models. Cancer Res 67(9):4295–4302CrossRef

99.

Sevignani C, Calin GA et al (2006) Mammalian microRNAs: a small world for fine-tuning gene expression. Mamm Genome 17(3):189–202CrossRef

100.

Shiraishi K, Shimura T et al (2002) Persistent induction of somatic reversions of the pink-eyed unstable mutation in F1 mice born to fathers irradiated at the spermatozoa stage. Radiat Res 157(6):661–667CrossRef

101.

Slovinska L, Elbertova A et al (2004) Transmission of genome damage from irradiated male rats to their progeny. Mutat Res 559(1–2):29–37

102.

Streffer C (2006) Transgenerational transmission of radiation damage: genomic instability and congenital malformation. J Radiat Res (Tokyo) 47(Suppl B):B19–B24CrossRef

103.

Tamminga J, Koturbash I et al (2008) Paternal cranial irradiation induces distant bystander DNA damage in the germline and leads to epigenetic alterations in the offspring. Cell Cycle 7(9):1238–1245CrossRef

104.

Tawa R, Kimura Y et al (1998) Effects of X-ray irradiation on genomic DNA methylation levels in mouse tissues. J Radiat Res (Tokyo) 39(4):271–278CrossRef

105.

Tryndyak VP, Kovalchuk O et al (2006) Loss of DNA methylation and histone H4 lysine 20 trimethylation in human breast cancer cells is associated with aberrant expression of DNA methyltransferase 1, Suv4-20 h2 histone methyltransferase and methyl-binding proteins. Cancer Biol Ther 5(1):65–70CrossRef

106.

Valerie K, Yacoub A et al (2007) Radiation-induced cell signaling: inside-out and outside-in. Mol Cancer Ther 6(3):789–801CrossRef

107.

Van Speybroeck L (2002) From Epigenesis to Epigenetics. Ann N Y Acad Sci 981(1):61–81CrossRef

108.

Volinia S, Calin GA et al (2006) A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci USA 103(7):2257–2261CrossRef

109.

Vorobtsova IE, Kitaev EM (1988) Urethane-induced lung adenomas in the first-generation progeny of irradiated male mice. Carcinogenesis 9(11):1931–1934CrossRef

110.

Vorobtsova IE, Aliyakparova LM et al (1993) Promotion of skin tumors by 12-O-tetradecanoylphorbol-13-acetate in two generations of descendants of male mice exposed to X-ray irradiation. Mutat Res 287(2):207–216CrossRef

111.

Wade PA, Archer TK (2006) Epigenetics: environmental instructions for the genome. Environ Health Perspect 114(3):A140–A141CrossRef

112.

Weber M, Schubeler D (2007) Genomic patterns of DNA methylation: targets and function of an epigenetic mark. Curr Opin Cell Biol 19(3):273–280CrossRef

113.

Weidman JR, Dolinoy DC et al (2007) Cancer susceptibility: epigenetic manifestation of environmental exposures. Cancer J 13(1):9–16CrossRef

114.

Wiemer EA (2007) The role of microRNAs in cancer: no small matter. Eur J Cancer 43(10):1529–1544CrossRef

Titel: Role of Epigenetic Changes in Radiation-Induced Genome Instability
verfasst von: Slava Ilnytskyy
Jody Filkowski
Olga Kovalchuk
Verlag: Springer Netherlands
Buch: Radiobiology and Environmental Security
Print ISBN: 978-94-007-1938-5

Electronic ISBN: 978-94-007-1939-2

Copyright-Jahr: 2012
DOI: https://doi.org/10.1007/978-94-007-1939-2_6

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