PATM and γH2AX Are Effective Radiation Biomarkers in Assessing the Radiosensitivity of C in Human Tumor Cells

Overview

Journal Cancer Cell Int

Publisher Biomed Central

Date 2017 Apr 29

PMID 28450809

Citations 15

Authors

Jin Zhao

Zhong Guo

Shuyan Pei

Lei Song

Chenjing Wang

Jianxiu Ma

Long Jin

Yanqing Ma

Renke He

Jianbin Zhong

Ying Ma

Hong Zhang

Affiliations

Soon will be listed here.

Abstract

Background: Tumour radiosensitivity would be particularly useful in optimizing the radiation dose during radiotherapy. The aim of the current study was to evaluate the potential value of phosphorylated H2AX (γH2AX) and ATM (pATM) in assessing C radiosensitivity of tumour cells.

Methods: Human cervical carcinoma HeLa cells, hepatoma HepG2 cells, and mucoepidermoid carcinoma MEC-1 cells were irradiated with different doses of C. The survival fraction was assayed with clonogenic survival method and the foci of γH2AX and pATM was visualized using immunocytochemical methods. Flow cytometry was used to assay γH2AX, pATM and the cell cycle.

Results: The survival fraction decreased immediately in dose-dependent manner, but in turn, significantly increased during 24 h after C irradiation. Both γH2AX and pATM foci accumulated linearly with doses and with a maximum induction at 0.5 h for γH2AX and 0.5 or 4 h for pATM, respectively, and a fraction foci kept for 24 h. The expression of γH2AX and pATM was in relation to cell cycle. The G0/G1 phase cells had the highest expression of γH2AX after 0.5 h irradiation and then decreased to a lower level at 24 h after irradiation. An obvious increase of pATM in G2/M phase was shown after 24 h of 2 and 4 Gy irradiation. The significant G2/M phase arrest was shown. There was a close relationship between the clonogenic survival and γH2AX and pATM expression both in timing and dose in response to C.

Conclusions: The rate of γH2AX and pATM formation and loss may be an important factor in the response of cells to C. pATM and γH2AX are effective radiation biomarkers in assessing the radiosensitivity of C in human tumor cells.

Citing Articles

The effects of carbon-ion beam irradiation on three-dimensional in vitro models of normal oral mucosa and oral cancer: development of a novel tool to evaluate cancer therapy.

Naito E, Igawa K, Takada S, Haga K, Yortchan W, Suebsamarn O In Vitro Cell Dev Biol Anim. 2024; 60(10):1184-1199.

PMID: 39110152 DOI: 10.1007/s11626-024-00958-4.

Evaluation of X-ray and carbon-ion beam irradiation with chemotherapy for the treatment of cervical adenocarcinoma cells in 2D and 3D cultures.

Sekihara K, Himuro H, Saito N, Ota Y, Kouro T, Kusano Y Cancer Cell Int. 2022; 22(1):391.

PMID: 36494817 PMC: 9733259. DOI: 10.1186/s12935-022-02810-9.

Tightly Focused Femtosecond Laser Radiation Induces DNA Double-Strand Breaks in Human Tumor Cells.

Fedotov Y, Zalessky A, Yashkina E, Zrilova Y, Osipov A Bull Exp Biol Med. 2022; 172(6):743-746.

PMID: 35501653 DOI: 10.1007/s10517-022-05469-4.

Detection of Radiation-Induced DNA Damage in Breast Cancer Patients by Using Gamma H2AX Biomarker: A Possible Correlation with Their Body Mass Index.

Mahmoud A, E Hassan A, Ali A, Hassan N, Yousif A, Elbashir F Genome Integr. 2022; 13:1.

PMID: 35444787 PMC: 9015078. DOI: 10.4103/genint.genint_1_22.

Biological Effects of Monoenergetic Carbon Ions and Their Associated Secondary Particles.

Buglewicz D, Walsh K, Hirakawa H, Kitamura H, Fujimori A, Kato T Front Oncol. 2022; 12:788293.

PMID: 35251969 PMC: 8892238. DOI: 10.3389/fonc.2022.788293.

References

Ismail I, Wadhra T, Hammarsten O . An optimized method for detecting gamma-H2AX in blood cells reveals a significant interindividual variation in the gamma-H2AX response among humans. Nucleic Acids Res. 2007; 35(5):e36. PMC: 1865071. DOI: 10.1093/nar/gkl1169. View

Keogh M, Kim J, Downey M, Fillingham J, Chowdhury D, Harrison J . A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery. Nature. 2005; 439(7075):497-501. DOI: 10.1038/nature04384. View

Tanaka T, Kurose A, Halicka H, Traganos F, Darzynkiewicz Z . 2-deoxy-D-glucose reduces the level of constitutive activation of ATM and phosphorylation of histone H2AX. Cell Cycle. 2006; 5(8):878-82. DOI: 10.4161/cc.5.8.2681. View

Takahashi A, Yamakawa N, Kirita T, Omori K, Ishioka N, Furusawa Y . DNA damage recognition proteins localize along heavy ion induced tracks in the cell nucleus. J Radiat Res. 2008; 49(6):645-52. DOI: 10.1269/jrr.08007. View

Osipov A, Pustovalova M, Grekhova A, Eremin P, Vorobyova N, Pulin A . Low doses of X-rays induce prolonged and ATM-independent persistence of γH2AX foci in human gingival mesenchymal stem cells. Oncotarget. 2015; 6(29):27275-87. PMC: 4694989. DOI: 10.18632/oncotarget.4739. View

Chen Z, Xiao Z, Gu W, Xue J, Bui M, Kovar P . Selective Chk1 inhibitors differentially sensitize p53-deficient cancer cells to cancer therapeutics. Int J Cancer. 2006; 119(12):2784-94. DOI: 10.1002/ijc.22198. View

MacPhail S, Banath J, Yu T, Chu E, Lambur H, Olive P . Expression of phosphorylated histone H2AX in cultured cell lines following exposure to X-rays. Int J Radiat Biol. 2003; 79(5):351-8. DOI: 10.1080/0955300032000093128. View

Nambiar D, Rajamani P, Deep G, Jain A, Agarwal R, Singh R . Silibinin Preferentially Radiosensitizes Prostate Cancer by Inhibiting DNA Repair Signaling. Mol Cancer Ther. 2015; 14(12):2722-34. PMC: 4674330. DOI: 10.1158/1535-7163.MCT-15-0348. View

Rogakou E, Boon C, Redon C, Bonner W . Megabase chromatin domains involved in DNA double-strand breaks in vivo. J Cell Biol. 1999; 146(5):905-16. PMC: 2169482. DOI: 10.1083/jcb.146.5.905. View

10.

Turinetto V, Giachino C . Multiple facets of histone variant H2AX: a DNA double-strand-break marker with several biological functions. Nucleic Acids Res. 2015; 43(5):2489-98. PMC: 4357700. DOI: 10.1093/nar/gkv061. View

11.

Nakajima N, Brunton H, Watanabe R, Shrikhande A, Hirayama R, Matsufuji N . Visualisation of γH2AX foci caused by heavy ion particle traversal; distinction between core track versus non-track damage. PLoS One. 2013; 8(8):e70107. PMC: 3743843. DOI: 10.1371/journal.pone.0070107. View

12.

Meyer B, Voss K, Tobias F, Jakob B, Durante M, Taucher-Scholz G . Clustered DNA damage induces pan-nuclear H2AX phosphorylation mediated by ATM and DNA-PK. Nucleic Acids Res. 2013; 41(12):6109-18. PMC: 3695524. DOI: 10.1093/nar/gkt304. View

13.

Banuelos C, Banath J, MacPhail S, Zhao J, Reitsema T, Olive P . Radiosensitization by the histone deacetylase inhibitor PCI-24781. Clin Cancer Res. 2007; 13(22 Pt 1):6816-26. DOI: 10.1158/1078-0432.CCR-07-1126. View

14.

Horn S, Brady D, Prise K . Alpha particles induce pan-nuclear phosphorylation of H2AX in primary human lymphocytes mediated through ATM. Biochim Biophys Acta. 2015; 1853(10 Pt A):2199-206. DOI: 10.1016/j.bbamcr.2015.06.010. View

15.

Siddiqui M, Francois M, Fenech M, Leifert W . γH2AX responses in human buccal cells exposed to ionizing radiation. Cytometry A. 2014; 87(4):296-308. DOI: 10.1002/cyto.a.22607. View

16.

Xue L, Furusawa Y, Yu D . ATR signaling cooperates with ATM in the mechanism of low dose hypersensitivity induced by carbon ion beam. DNA Repair (Amst). 2015; 34:1-8. DOI: 10.1016/j.dnarep.2015.07.001. View

17.

Schmid T, Dollinger G, Beisker W, Hable V, Greubel C, Auer S . Differences in the kinetics of gamma-H2AX fluorescence decay after exposure to low and high LET radiation. Int J Radiat Biol. 2010; 86(8):682-91. DOI: 10.3109/09553001003734543. View

18.

Takahashi M, Hirakawa H, Yajima H, Izumi-Nakajima N, Okayasu R, Fujimori A . Carbon ion beam is more effective to induce cell death in sphere-type A172 human glioblastoma cells compared with X-rays. Int J Radiat Biol. 2014; 90(12):1125-32. DOI: 10.3109/09553002.2014.927933. View

19.

Nickoloff J . Photon, light ion, and heavy ion cancer radiotherapy: paths from physics and biology to clinical practice. Ann Transl Med. 2016; 3(21):336. PMC: 4691008. DOI: 10.3978/j.issn.2305-5839.2015.12.18. View

20.

Okayasu R . Repair of DNA damage induced by accelerated heavy ions--a mini review. Int J Cancer. 2011; 130(5):991-1000. DOI: 10.1002/ijc.26445. View