Skip to main content
SpringerLink
Log in

Alterations in histone acetylation following exposure to 60Co γ-rays and their relationship with chromosome damage in human lymphoblastoid cells

  • Original Article
  • Published:
Radiation and Environmental Biophysics Aims and scope Submit manuscript

Abstract

Chromosome damage is related to DNA damage and erroneous repair. It can cause cell dysfunction and ultimately induce carcinogenesis. Histone acetylation is crucial for regulating chromatin structure and DNA damage repair. Ionizing radiation (IR) can alter histone acetylation. However, variations in histone acetylation in response to IR exposure and the relationship between histone acetylation and IR-induced chromosome damage remains unclear. Hence, this study investigated the variation in the total acetylation levels of H3 and H4 in human lymphocytes exposed to 0–2 Gy 60Co γ-rays. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase (HDAC) inhibitor, was added to modify the histone acetylation state of irradiated cells. Then, the total acetylation level, enzyme activity, dicentric plus centric rings (dic + r) frequencies, and micronucleus (MN) frequencies of the treated cells were analyzed. Results indicated that the acetylation levels of H3 and H4 significantly decreased at 1 and 24 h, respectively, after radiation exposure. The acetylation levels of H3 and H4 in irradiated groups treated with SAHA were significantly higher than those in irradiated groups that were not treated with SAHA. SAHA treatment inhibited HDAC activity in cells exposed to 0–1 Gy 60Co γ-rays. SAHA treatment significantly decreased dic + r/cell and MN/cell in cells exposed to 0.5 or 1.0 Gy 60Co γ-rays relative to that in cells that did not receive SAHA treatment. In conclusion, histone acetylation is significantly affected by IR and is involved in chromosome damage induced by 60Co γ-radiation.

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
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Acharya MR, Sparreboom A, Venitz J, Figg WD (2005) Rational development of histone deacetylase inhibitors as anticancer agents: a review. Mol Pharmacol 68(4):917–932

    Article  Google Scholar 

  • Barjaktarovic Z, Merl-Pham J, Azimzadeh O, Kempf SJ, Raj K, Atkinson MJ, Tapio S (2017) Low-dose radiation differentially regulates protein acetylation and histone deacetylase expression in human coronary artery endothelial cells. Int J Radiat Biol 93(2):156–164

    Article  Google Scholar 

  • Battu A, Ray A, Wani AA (2011) ASF1A and ATM regulate H3K56-mediated cell-cycle checkpoint recovery in response to UV irradiation. Nucleic Acids Res 39(18):7931–7945

    Article  Google Scholar 

  • Blattmann C, Oertel S, Thiemann M, Dittmar A, Roth E, Kulozik AE, Ehemann V, Weichert W, Huber PE, Stenzinger A, Debus J (2015) Histone deacetylase inhibition sensitizes osteosarcoma to heavy ion radiotherapy. Radiat Oncol 10:146

    Article  Google Scholar 

  • Bull CF, Mayrhofer G, Zeegers D, Mun GL, Hande MP, Fenech MF (2012). Folate deficiency is associated with the formation of complex nuclear anomalies in the cytokinesis-block micronucleus cytome assay. Environ Mol Mutagen 53(4):311–323

    Article  Google Scholar 

  • Cedar H, Bergman Y (2009) Linking DNA methylation and histone modification: patterns and paradigms. Nat Rev Genet 10(5):295–304

    Article  Google Scholar 

  • Cerna D, Camphausen K, Tofilon P (2006) Histone deacetylation as a target for radiosensitization. Curr Top Dev Biol 73:173–204

    Article  Google Scholar 

  • Chen CC, Tyler J (2008) Chromatin reassembly signals the end of DNA repair. Cell Cycle 7(24):3792–3797

    Article  Google Scholar 

  • Di Tomaso MV, Gregoire E, Martínez-López W (2017) Effects of valproic acid on radiation-induced chromosomal aberrations in human lymphocytes. Genome Integr 8:4

    Article  Google Scholar 

  • Drummond D, Noble C, Kirpotin D, Guo Z, Scott G, Benz C (2005) Clinical development of histone deacetylase inhibitors as anticancer agents. Annu Rev Pharmacol Toxicol 45:495–528

    Article  Google Scholar 

  • Fenech M (2000) The in vitro micronucleus technique. Mutat Res 455(1–2):81–95

    Article  Google Scholar 

  • Fenech M (2010) The lymphocyte cytokinesis-block micronucleus cytome assay and its application in radiation biodosimetry. Health Phys 98(2):234 – 43

    Article  Google Scholar 

  • Gibney ER, Nolan CM (2010) Epigenetics and gene expression. Heredity 105(1):4–13

    Article  Google Scholar 

  • Gong F, Miller KM (2013) Mammalian DNA repair: HATs and HDACs make their mark through histone acetylation. Mutat Res 750(1–2):23–30

    Article  Google Scholar 

  • Groth A, Rocha W, Verreault A, Almouzni G (2007) Chromatin challenges during DNA replication and repair. Cell 128(4):721 – 33

    Article  Google Scholar 

  • Guo R, Chen J, Mitchell DL, Johnson DG (2011) GCN5 and E2F1 stimulate nucleotide excision repair by promoting H3K9 acetylation at sites of damage. Nucleic Acids Res 39(4):1390–1397

    Article  Google Scholar 

  • Hefferin ML, Tomkinson AE (2005) Mechanism of DNA double-strand break repair by non-homologous end joining. DNA Repair 4(6):639–648

    Article  Google Scholar 

  • Hoeijmakers JH (2001) DNA repair mechanisms. Maturitas 38(1):17–22 (discussion 22–23)

    Article  Google Scholar 

  • Hsiao KY, Mizzen CA (2013) Histone H4 deacetylation facilitates 53BP1 DNA damage signaling and double-strand break repair. J Mol Cell Biol 5(3):157–165

    Article  Google Scholar 

  • Hunt CR, Ramnarain D, Horikoshi N, Iyengar P, Pandita RK, Shay JW, Pandita TK (2013) Histone modifications and DNA double-strand break repair after exposure to ionizing radiations. Radiat Res 179(4):383–392

    Article  ADS  Google Scholar 

  • International Atomic Energy Agency (2011) Cytogenetic dosimetry: application in preparedness for and response to radiation emergencies. IAEA, Vienna

    Google Scholar 

  • Jazayeri A, McAinsh AD, Jackson SP (2004) Saccharomyces cerevisiae Sin3p facilitates DNA double-strand break repair. PNAS 101:1644–1649

    Article  ADS  Google Scholar 

  • Jeggo PA, Lobrich M (2006) Contribution of DNA repair and cell cycle checkpoint arrest to the maintenance of genomic stability. DNA Repair 5(9–10):1192–1198

    Article  Google Scholar 

  • Li A, Yu Y, Lee SC, Ishibashi T, Lees-Miller SP, Ausio J (2010) Phosphorylation of histone H2A.X by DNA-dependent protein kinase is not affected by core histone acetylation, but it alters nucleosome stability and histone H1 binding. J Biol Chem 285(23):17778–17788

    Article  Google Scholar 

  • Mahaney BL, Meek K, Lees-Miller SP (2009) Repair of ionizing radiation-induced DNA double-strand breaks by non-homologous end-joining. Biochem J 417(3):639–650

    Article  Google Scholar 

  • Maroschik B, Gurtler A, Kramer A, Rossler U, Gomolka M, Hornhardt S, Mortl S, Friedl AA (2014) Radiation-induced alterations of histone post-translational modification levels in lymphoblastoid cell lines. Radiat Oncol 9:15

    Article  Google Scholar 

  • Miller KM, Tjeertes JV, Coates J, Legube G, Polo SE, Britton S, Jackson SP (2010) Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA nonhomologous end-joining. Nat Struct Mol Biol 17(9):1144–1151

    Article  Google Scholar 

  • Niewolik D, Pannicke U, Lu H, Ma Y, Wang L, Kulesza P, Zandi E, Lieber M, Schwarz K (2006) DNA-PKcs dependence of Artemis endonucleolytic activity, differences between hairpins and 5′ or 3′ overhangs. J Biol Chem 281:33900–33909

    Article  Google Scholar 

  • Ogiwara H, Ui A, Otsuka A, Satoh H, Yokomi I, Nakajima S, Yasui A, Yokota J, Kohno T (2011) Histone acetylation by CBP and p300 at double-strand break sites facilitates SWI/SNF chromatin remodeling and the recruitment of non-homologous end joining factors. Oncogene 30(18):2135–2146

    Article  Google Scholar 

  • Price BD, D’Andrea AD (2013) Chromatin remodeling at DNA double-strand breaks. Cell 152(6):1344–1354

    Article  Google Scholar 

  • Ramanathan B, Smerdon MJ (1989) Enhanced DNA repair synthesis in hyperacetylated nucleosomes. J Biol Chem 264(19):11026–11034

    Google Scholar 

  • Roberts SA, Ramsden DA (2007) Loading of the nonhomologous end joining factor, Ku, on protein-occluded DNA ends. J Biol Chem 282(14):10605–10613

    Article  Google Scholar 

  • Rossetto D, Truman AW, Kron SJ, Cote J (2010) Epigenetic modifications in double-strand break DNA damage signaling and repair. Clin Cancer Res 16(18):4543–4552

    Article  Google Scholar 

  • Rothkamm K, Kruger I, Thompson LH, Lobrich M (2003) Pathways of DNA double-strand break repair during the mammalian cell cycle. Mol Cell Biol 23(16):5706–5715

    Article  Google Scholar 

  • Seo SK, Jin HO, Woo SH, Kim YS, An S, Lee JH, Hong SI, Lee KH, Choe TB, Park IC (2011) Histone deacetylase inhibitors sensitize human non-small cell lung cancer cells to ionizing radiation through acetyl p53-mediated c-myc down-regulation. J Thorac Oncol 6(8):1313–1319

    Article  Google Scholar 

  • Shahbazian MD, Grunstein M (2007) Functions of site-specific histone acetylation and deacetylation. Annu Rev Biochem 76:75–100

    Article  Google Scholar 

  • Sharma GG, So S, Gupta A, Kumar R, Cayrou C, Avvakumov N, Bhadra U, Pandita RK, Porteus MH, Chen DJ, Cote J, Pandita TK (2010) MOF and histone H4 acetylation at lysine 16 are critical for DNA damage response and double-strand break repair. Mol Cell Biol 30(14):3582–3595

    Article  Google Scholar 

  • Sun J, Lee KJ, Davis AJ, Chen DJ (2012) Human Ku70/80 protein blocks exonuclease 1-mediated DNA resection in the presence of human Mre11 or Mre11/Rad50 protein complex. J Biol Chem 287(7):4936–4945

    Article  Google Scholar 

  • Tjeertes JV, Miller KM, Jackson SP (2009) Screen for DNA-damage-responsive histone modifications identifies H3K9Ac and H3K56Ac in human cells. EMBO J 28(13):1878–1889

    Article  Google Scholar 

  • van Attikum H, Gasser SM (2009) Crosstalk between histone modifications during the DNA damage response. Trends Cell Biol 19(5):207–217

    Article  Google Scholar 

  • Verreault A (2000) De novo nucleosome assembly: new pieces in an old puzzle. Genes Dev 14(12):1430–1438

    Google Scholar 

  • Wyman C, Kanaar R (2004) Homologous recombination: down to the wire. Curr Biol 14(15):R629–R631

    Article  Google Scholar 

  • Zhang X, Kluz T, Gesumaria L, Matsui MS, Costa M, Sun H (2016) Solar simulated ultraviolet radiation induces global histone hypoacetylation in human keratinocytes. PLoS One 11(2):e0150175

    Article  Google Scholar 

  • Zhao H, Lu X, Li S, Chen DQ, Liu QJ (2014) Characteristics of nucleoplasmic bridges induced by 60Co gamma-rays in human peripheral blood lymphocytes. Mutagenesis 29(1):49–54

    Article  Google Scholar 

  • Zhong HM, Ding QH, Chen WP, Luo RB (2013) Vorinostat, a HDAC inhibitor, showed anti-osteoarthritic activities through inhibition of iNOS and MMP expression, p38 and ERK phosphorylation and blocking NF-κB nuclear translocation. Int Immunopharmacol 17(2):329–335

    Article  Google Scholar 

Download references

Acknowledgements

All authors wish to thank Drs. De-Qing Chen and Ling Gao for their important suggestions. This study was funded by National Natural Science Foundation of China (No. 81573081 to Q.-J. L.) and Youth Science Research Foundation of NIRP, China CDC (No. 2017-002 to X.-L. T.).

Funding

This study was funded by National Natural Science Foundation of China (No. 81573081 to Q.-J. L.) and Youth Science Research Foundation of NIRP, China CDC (No. 2017-002 to X.-L. T.).

Author information

Authors and Affiliations

  1. China CDC Key Laboratory of Radiation Protection and Nuclear Emergency, National Institute for Radiological Protection, Chinese Center for Disease Control and Prevention, Beijing, 100088, People’s Republic of China

    Xue-Lei Tian, Xue Lu, Jiang-Bin Feng, Tian-Jing Cai, Shuang Li, Mei Tian & Qing-Jie Liu

Authors
  1. Xue-Lei Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xue Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jiang-Bin Feng
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tian-Jing Cai
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shuang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mei Tian
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Qing-Jie Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Qing-Jie Liu.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 19 KB)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tian, XL., Lu, X., Feng, JB. et al. Alterations in histone acetylation following exposure to 60Co γ-rays and their relationship with chromosome damage in human lymphoblastoid cells. Radiat Environ Biophys 57, 215–222 (2018). https://doi.org/10.1007/s00411-018-0742-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00411-018-0742-9

Keywords

Search

Navigation