Effects of ionizing radiation on DNA methylation: from experimental biology to clinical applications

References

• Agrawal V, Alpini SEJ, Stone EM, Frenkel EP, Frankel AE. 2012. Targeting methionine auxotrophy in cancer: discovery exploration. Expert Opin Biol Ther. 12:53–61.
   PubMed Web of Science ®Google Scholar
• Aguilera O, Fernández AF, Muñoz A, Fraga MF. 2010. Epigenetics and environment: a complex relationship. J Appl Physiol. 109:243–251.
   PubMed Web of Science ®Google Scholar
• Antwih DA, Gabbara KM, Lancaster WD, Ruden DM, Zielske SP. 2013. Radiation-induced epigenetic DNA methylation modification of radiation-response pathways. Epigenetics-Us. 8:839–848.
   PubMed Web of Science ®Google Scholar
• Aypar U, Morgan WF, Baulch JE. 2011. Radiation-induced epigenetic alterations after low and high LET irradiations. Mutat Res. 707:24–33.
   PubMed Web of Science ®Google Scholar
• Batra V, Kesavan V, Mishra KP. 2004. Modulation of enzymes involved in folate dependent one-carbon metabolism by gamma-radiation stress in mice. J Radiat Res. 45:527–533.
   PubMed Web of Science ®Google Scholar
• Batra V, Mishra KP. 2007. Modulation of DNA methyltransferase profile by methyl donor starvation followed by gamma irradiation. Mol Cell Biochem. 294:181–187.
   PubMed Web of Science ®Google Scholar
• Batra V, Sridhar S, Devasagayam TPA. 2010. Enhanced one-carbon flux towards DNA methylation: effect of dietary methyl supplements against gamma-radiation-induced epigenetic modifications. Chem-Biol Interact. 183:425–433.
   PubMed Web of Science ®Google Scholar
• Batra V, Verma P. 2014. Dietary L-methionine supplementation mitigates gamma-radiation induced global DNA hypomethylation: enhanced metabolic flux towards S-adenosyl-L-methionine (SAM) biosynthesis increases genomic methylation potential. Food Chem Toxicol. 69:46–54.
   PubMed Web of Science ®Google Scholar
• Baubec T, Schübeler D. 2014. Genomic patterns and context specific interpretation of DNA methylation. Curr Opin Genet Dev. 25:85–92.
   PubMed Web of Science ®Google Scholar
• Belinsky SA, Klinge DM, Liechty KC, March TH, Kang T, Gilliland FD, Sotnic N, Adamova G, Rusinova G, Telnov V. 2004. Plutonium targets the p16 gene for inactivation by promoter hypermethylation in human lung adenocarcinoma. Carcinogenesis. 25:1063–1067.
   PubMed Web of Science ®Google Scholar
• Blakely EA, Kronenberg A. 1998. Heavy-ion radiobiology: new approaches to delineate mechanisms underlying enhanced biological effectiveness. Radiat Res. 150:S126–S145.
   PubMed Web of Science ®Google Scholar
• Brenner DJ. 2010. Slowing the increase in the population dose resulting from CT scans. Radiat Res. 174:809–815.
   PubMed Web of Science ®Google Scholar
• Brieger J, Mann SA, Pongsapich W, Koutsimpelas D, Fruth K, Mann WJ. 2012. Pharmacological genome demethylation increases radiosensitivity of head and neck squamous carcinoma cells. Int J Mol Med. 29:505–509.
   PubMed Web of Science ®Google Scholar
• Bujko M, Musialik E, Olbromski R, Przestrzelska M, Libura M, Pastwinska A, Juszczynski P, Zwierzchowski L, Baranowski P, Siedlecki JA. 2014. Repetitive genomic elements and overall DNA methylation changes in acute myeloid and childhood B-cell lymphoblastic leukemia patients. Int J Hematol. 100:79–87.
   PubMed Web of Science ®Google Scholar
• Cavuoto P, Fenech MF. 2012. A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension. Cancer Treat Rev. 38:726–736.
   PubMed Web of Science ®Google Scholar
• Cellarier E, Durando X, Vasson MP, Farges MC, Demiden A, Maurizis JC, Madelmont JC, Chollet P. 2003. Methionine dependency and cancer treatment. Cancer Treat Rev. 29:489–499.
   PubMed Web of Science ®Google Scholar
• Christofidou-Solomidou M, Pietrofesa RA, Arguiri E, Schweitzer KS, Berdyshev EV, Mccarthy M, Corbitt A, Alwood JS, Yu Y, Globus RK, et al. 2015. Space radiation-associated lung injury in a murine model. Am J Physiol Lung Cell Mol Physiol. 308:L416–L428.
   PubMed Web of Science ®Google Scholar
• Cortessis VK, Thomas DC, Levine AJ, Breton CV, Mack TM, Siegmund KD, Haile RW, Laird PW. 2012. Environmental epigenetics: prospects for studying epigenetic mediation of exposure-response relationships. Hum Genet. 131:1565–1589.
   PubMed Web of Science ®Google Scholar
• de Koning APJ, Gu WJ, Castoe TA, Batzer MA, Pollock DD. 2011. Repetitive elements may comprise over two-thirds of the human genome. PloS Genet. 7:e1002384. doi: 10.1371/journal.pgen.1002384
   PubMed Web of Science ®Google Scholar
• Dote H, Cerna D, Burgan WE, Carter DJ, Cerra MA, Hollingshead MG, Camphausen K, Tofilon PJ. 2005. Enhancement of in vitro and in vivo tumor cell radiosensitivity by the DNA methylation inhibitor zebularine. Clin Cancer Res. 11:4571–4579.
   PubMed Web of Science ®Google Scholar
• Durando X, Farges MC, Buc E, Abrial C, Petorin-Lesens C, Gillet B, Vasson MP, Pezet D, Chollet P, Thivat E. 2010. Dietary methionine restriction with FOLFOX regimen as first line therapy of metastatic colorectal cancer: a feasibility study. Oncology-Basel. 78:205–209.
   PubMed Web of Science ®Google Scholar
• Durando X, Thivat E, Gimbergues P, Cellarier E, Abrial C, Dib M, Tacca O, Chollet P. 2008. [Methionine dependency of cancer cells: a new therapeutic approach?]. B Cancer. 95:69–76.
   Google Scholar
• Durante M. 2014. New challenges in high-energy particle radiobiology. Br J Radiol. 87(1035):20130626. doi: 10.1259/bjr.20130626
   PubMed Web of Science ®Google Scholar
• Durante M, Cucinotta FA. 2008. Heavy ion carcinogenesis and human space exploration. Nat Rev Cancer. 8:465–472.
   PubMed Web of Science ®Google Scholar
• Ehrlich M, Ehrlich KC. 2014. DNA cytosine methylation and hydroxymethylation at the borders. Epigenomics-UK. 6:563–566.
   PubMed Web of Science ®Google Scholar
• Esteller M, Garcia-Foncillas J, Andion E, Goodman SN, Hidalgo OF, Vanaclocha V, Baylin SB, Herman JG. 2000. Inactivation of the DNA-repair gene MGMT and the clinical response of gliomas to alkylating agents. N Engl J Med. 343:1350–1354.
   PubMed Web of Science ®Google Scholar
• Feil R, Fraga MF. 2012. Epigenetics and the environment: emerging patterns and implications. Nat Rev Genet. 13:97–109.
   PubMed Web of Science ®Google Scholar
• Gebhard C, Schwarzfischer L, Pham TH, Schilling E, Klug M, Andreesen R, Rehli M. 2006. Genome-wide profiling of CpG methylation identifies novel targets of aberrant hypermethylation in myeloid leukemia. Cancer Res. 66:6118–6128.
   PubMed Web of Science ®Google Scholar
• Giotopoulos G, McCormick C, Cole C, Zanker A, Jawad M, Brown R, Plumb M. 2006. DNA methylation during mouse hemopoietic differentiation and radiation-induced leukemia. Exp Hematol. 34:1462–1470.
   PubMed Web of Science ®Google Scholar
• Girdhani S, Sachs R, Hlatky L. 2013. Biological effects of proton radiation: what we know and don’t know. Radiat Res. 179:257–272.
   PubMed Web of Science ®Google Scholar
• Goetz W, Morgan MNM, Baulch JE. 2011. The effect of radiation quality on genomic DNA methylation profiles in irradiated human cell lines. Radiat Res. 175:575–587.
   PubMed Web of Science ®Google Scholar
• Gravina GL, Festuccia C, Marampon F, Popov VM, Pestell RG, Zani BM, Tombolini V. 2010. Biological rationale for the use of DNA methyltransferase inhibitors as new strategy for modulation of tumor response to chemotherapy and radiation. Mol Cancer. 9:305. doi: 10.1186/1476-4598-9-305
   PubMed Web of Science ®Google Scholar
• Guénin S, Morvan D, Thivat E, Stepien G, Demidem A. 2009. Combined methionine deprivation and chloroethylnitrosourea have time-dependent therapeutic synergy on melanoma tumors that NMR spectroscopy-based metabolomics explains by methionine and phospholipid metabolism reprogramming. Nutr Cancer. 61:518–529.
   PubMed Web of Science ®Google Scholar
• Heyn H, Esteller M. 2012. DNA methylation profiling in the clinic: applications and challenges. Nat Rev Genet. 13:679–692.
   PubMed Web of Science ®Google Scholar
• Hofstetter B, Niemierko A, Forrer C, Benhattar J, Albertini V, Pruschy M, Bosman FT, Catapano CV, Ciernik IF. 2010. Impact of genomic methylation on radiation sensitivity of colorectal carcinoma. Int J Radiat Oncol Biol Phys. 76:1512–1519.
   PubMed Web of Science ®Google Scholar
• Hondorp ER, Matthews RG. 2006. Methionine. EcoSal plus. 2. doi: 10.1128/ecosalplus.3.6.1.7
   Google Scholar
• Iwagami S, Baba Y, Watanabe M, Shigaki H, Miyake K, Ishimoto T, Iwatsuki M, Sakamaki K, Ohashi Y, Baba H. 2013. LINE-1 Hypomethylation is associated with a poor prognosis among patients with curatively resected esophageal squamous cell carcinoma. Ann Surg. 257:449–455.
   PubMed Web of Science ®Google Scholar
• Jangiam W, Tungjai M, Rithidech KN. 2015. Induction of chronic oxidative stress, chronic inflammation and aberrant patterns of DNA methylation in the liver of titanium-exposed CBA/CaJ mice. Int J Radiat Biol. 91:389–398.
   PubMed Web of Science ®Google Scholar
• Jiang W, Li YQ, Liu N, Sun Y, He QM, Jiang N, Xu YF, Chen L, Ma J. 2014. 5-Azacytidine enhances the radiosensitivity of CNE2 and SUNE1 cells in vitro and in vivo possibly by altering DNA methylation. PLoS One. 9:e93273. doi: 10.1371/journal.pone.0093273
   PubMed Web of Science ®Google Scholar
• Johnson KC, Koestler DC, Fleischer T, Chen PP, Jenson EG, Marotti JD, Onega T, Kristensen VN, Christensen BC. 2015. DNA methylation in ductal carcinoma in situ related with future development of invasive breast cancer. Clin Epigenet. 7:75. doi: 10.1186/s13148-015-0094-0
   Web of Science ®Google Scholar
• Jones PA. 2012. Functions of DNA methylation: islands, start sites, gene bodies and beyond. Nat Rev Genet. 13:484–492.
   PubMed Web of Science ®Google Scholar
• Kalinich JF, Catravas GN, Snyder SL. 1989. The effect of gamma radiation on DNA methylation. Radiat Res. 117:185–197.
   PubMed Web of Science ®Google Scholar
• Kim EH, Park AK, Dong SM, Ahn JH, Park WY. 2010. Global analysis of CpG methylation reveals epigenetic control of the radiosensitivity in lung cancer cell lines. Oncogene. 29:4725–4731.
   PubMed Web of Science ®Google Scholar
• Kim HJ, Kim JH, Chie EK, Young PD, Kim IA, Kim IH. 2012. DNMT (DNA methyltransferase) inhibitors radiosensitize human cancer cells by suppressing DNA repair activity. Radiat Oncol. 7:39. doi: 10.1186/1748-717X-7-39
   Web of Science ®Google Scholar
• Kokkinakis DM, Brickner AG, Kirkwood JM, Liu XY, Goldwasser JE, Kastrama A, Sander C, Bocangel D, Chada S. 2006. Mitotic arrest, apoptosis, and sensitization to chemotherapy of melanomas by methionine deprivation stress. Mol Cancer Res. 4:575–589.
   PubMed Web of Science ®Google Scholar
• Kontic M, Stojsic J, Jovanovic D, Bunjevacki V, Ognjanovic S, Kuriger J, Puumala S, Nelson HH. 2012. Aberrant promoter methylation of CDH13 and MGMT genes is associated with clinicopathologic characteristics of primary non-small-cell lung carcinoma. Clin Lung Cancer. 13:297–303.
   PubMed Web of Science ®Google Scholar
• Koturbash I, Beland FA, Pogribny IP. 2011a. Role of epigenetic events in chemical carcinogenesis-a justification for incorporating epigenetic evaluations in cancer risk assessment. Toxicol Mech Meth. 21:289–297.
   PubMed Web of Science ®Google Scholar
• Koturbash I, Boyko A, Rodriguez-Juarez R, McDonald RJ, Tryndyak VP, Kovalchuk I, Pogribny IP, Kovalchuk O. 2007. Role of epigenetic effectors in maintenance of the long-term persistent bystander effect in spleen in vivo. Carcinogenesis. 28:1831–1838.
   PubMed Web of Science ®Google Scholar
• Koturbash I, Kutanzi K, Hendrickson K, Rodriguez-Juarez R, Kogosov D, Kovalchuk O. 2008. Radiation-induced bystander effects in vivo are sex-specific. Mutat Res. 642:28–36.
   PubMed Web of Science ®Google Scholar
• Koturbash I, Loree J, Kutanzi K, Koganow C, Pogribny I, Kovalchuk O. 2008. In vivo bystander effect: cranial X-irradiation leads to elevated DNA damage, altered cellular proliferation and apoptosis, and increased p53 levels in shielded spleen. Int J Radiat Oncol. 70:554–562.
   PubMed Web of Science ®Google Scholar
• Koturbash I, Miousse IR, Sridharan V, Nzabarushimana E, Skinner CM, Melnyk SB, Pavliv O, Hauer-Jensen M, Nelson GA, Boerma M. 2016. Radiation-induced changes in DNA methylation of repetitive elements in the mouse heart. Mutat Res-Fund Mol M. 787:43–53.
   PubMed Web of Science ®Google Scholar
• Koturbash I, Pogribny I, Kovalchuk O. 2005. Stable loss of global DNA methylation in the radiation-target tissue – a possible mechanism contributing to radiation carcinogenesis? Biochem Biophys Res Commun. 337:526–533.
   PubMed Web of Science ®Google Scholar
• Koturbash I, Rugo RE, Hendricks CA, Loree J, Thibault B, Kutanzi K, Pogribny I, Yanch JC, Engelward BP, Kovalchuk O. 2006. Irradiation induces DNA damage and modulates epigenetic effectors in distant bystander tissue in vivo. Oncogene. 25:4267–4275.
   PubMed Web of Science ®Google Scholar
• Koturbash I, Zemp F, Kolb B, Kovalchuk O. 2011b. Sex-specific radiation-induced microRNAome responses in the hippocampus, cerebellum and frontal cortex in a mouse model. Mutat Res-Gen Tox En. 722:114–118.
   PubMed Web of Science ®Google Scholar
• Kovalchuk O, Burke P, Besplug J, Slovack M, Filkowski J, Pogribny I. 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. 548:75–84.
   PubMed Web of Science ®Google Scholar
• Kroeger H, Jelinek J, Estécio MRH, He R, Kondo K, Chung W, Zhang L, Shen LL, Kantarjian HM, Bueso-Ramos CE, et al. 2008. Aberrant CpG island methylation in acute myeloid leukemia is accentuated at relapse. Blood. 112:1366–1373.
   PubMed Web of Science ®Google Scholar
• Kuhmann C, Weichenhan D, Rehli M, Plass C, Schmezer P, Popanda O. 2011. DNA methylation changes in cells regrowing after fractioned ionizing radiation. Radiother Oncol. 101:116–121.
   PubMed Web of Science ®Google Scholar
• Lahtz C, Bates SE, Jiang Y, Li AX, Wu XW, Hahn MA, Pfeifer GP. 2012. Gamma irradiation does not induce detectable changes in DNA methylation directly following exposure of human cells. PLoS One. 7:e44858.
   PubMed Web of Science ®Google Scholar
• Lee E, Iskow R, Yang LX, Gokcumen O, Haseley P, Luquette LJ, Lohr JG, Harris CC, Ding L, Wilson RK, et al. 2012. Landscape of somatic retrotransposition in human cancers. Science. 337:967–971.
   PubMed Web of Science ®Google Scholar
• Lima F, Ding DC, Goetz W, Yang AJ, Baulch JE. 2014. High LET (56)Fe ion irradiation induces tissue-specific changes in DNA methylation in the mouse. Environ Mol Mutagen. 55:266–277.
   PubMed Web of Science ®Google Scholar
• Loree J, Koturbash I, Kutanzi K, Baker M, Pogribny I, Kovalchuk O. 2006. Radiation-induced molecular changes in rat mammary tissue: possible implications for radiation-induced carcinogenesis. Int J Radiat Biol. 82:805–815.
   PubMed Web of Science ®Google Scholar
• Lyon CM, Klinge DM, Liechty KC, Gentry FD, March TH, Kang T, Gilliland FD, Adamova G, Rusinova G, Telnov V, et al. 2007. Radiation-induced lung adenocarcinoma is associated with increased frequency of genes inactivated by promoter hypermethylation. Radiat Res. 168:409–414.
   PubMed Web of Science ®Google Scholar
• Ma S, Liu X, Jiao B, Yang Y, Liu X. 2010. Low-dose radiation-induced responses: focusing on epigenetic regulation. Int J Radiat Biol. 86:517–528.
   PubMed Web of Science ®Google Scholar
• Miousse IR, Chalbot MCG, Lumen A, Ferguson A, Kavouras IG, Koturbash I. 2015. Response of transposable elements to environmental stressors. Mutat Res Rev Mutat Res. 765:19–39.
   PubMed Web of Science ®Google Scholar
• Miousse IR, Koturbash I. 2015. The fine LINE: methylation drawing the cancer landscape. BioMed Res Int. 2015:131547.
   PubMed Web of Science ®Google Scholar
• Miousse IR, Shao LJ, Chang JH, Feng W, Wang YY, Allen AR, Turner J, Stewart B, Raber J, Zhou DH, et al. 2014. Exposure to low-dose Fe-56-ion radiation induces long-term epigenetic alterations in mouse bone marrow hematopoietic progenitor and stem cells. Radiat Res. 182:92–101.
   PubMed Web of Science ®Google Scholar
• Moding EJ, Kastan MB, Kirsch DG. 2013. Strategies for optimizing the response of cancer and normal tissues to radiation. Nat Rev Drug Discov. 12:526–542.
   PubMed Web of Science ®Google Scholar
• Momparler RL, Côté S, Momparler LF, Idaghdour Y. 2014. Epigenetic therapy of acute myeloid leukemia using 5-aza-2′-deoxycytidine (decitabine) in combination with inhibitors of histone methylation and deacetylation. Clin Epigenet. 6:19. doi: 10.1186/1868-7083-6-19
   PubMed Web of Science ®Google Scholar
• Mothersill C, Seymour C. 2012. Are epigenetic mechanisms involved in radiation-induced bystander effects? Front Genet. 3:74.
   PubMedGoogle Scholar
• Mouse Genome Sequencing Consortium, Waterston RH, Lindblad-Toh K, Birney E, Rogers J, Abril JF, Agarwal P, Agarwala R, Ainscough R, Alexandersson M, An P, et al. 2002. Initial sequencing and comparative analysis of the mouse genome. Nature. 420:520–562.
   PubMed Web of Science ®Google Scholar
• Nervi C, De Marinis E, Codacci-Pisanelli G. 2015. Epigenetic treatment of solid tumours: a review of clinical trials. Clin Epigenetics. Dec Epigenetics. 7:127.
   PubMed Web of Science ®Google Scholar
• Newman MR, Sykes PJ, Blyth BJ, Bezak E, Lawrence MD, Morel KL, Ormsby RJ. 2014b. The methylation of DNA repeat elements is sex-dependent and temporally different in response to X radiation in radiosensitive and radioresistant mouse strains. Radiat Res. 181:65–75.
   PubMed Web of Science ®Google Scholar
• Newman MR, Sykes PJ, Blyth BJ, Bezak E, Lawrence MD, Morel KL, Ormsby RJ. 2014a. A single whole-body low dose X-irradiation does not affect L1, B1 and IAP repeat element DNA methylation longitudinally. Plos One. 9:e93016.
   PubMed Web of Science ®Google Scholar
• Nikolaidis G, Raji OY, Markopoulou S, Gosney JR, Bryan J, Warburton C, Walshaw M, Sheard J, Field JK, Liloglou T. 2012. DNA methylation biomarkers offer improved diagnostic efficiency in lung cancer. Cancer Res. 72:5692–5701.
   PubMed Web of Science ®Google Scholar
• Niyazi M, Schnell O, Suchorska B, Schwarz SB, Ganswindt U, Geisler J, Bartenstein P, Kreth FW, Tonn JC, Eigenbrod S, et al. 2012. FET-PET assessed recurrence pattern after radio-chemotherapy in newly diagnosed patients with glioblastoma is influenced by MGMT methylation status. Radiother Oncol. 104:78–82.
   PubMed Web of Science ®Google Scholar
• Nüsgen N, Goering W, Dauksa A, Biswas A, Jamil MA, Dimitriou I, Sharma A, Singer H, Fimmers R, Frohlich H, et al. 2015. Inter-locus as well as intra-locus heterogeneity in LINE-1 promoter methylation in common human cancers suggests selective demethylation pressure at specific CpGs. Clin Epigenet. 7:17. doi: 10.1186/s13148-015-0051-y
   PubMed Web of Science ®Google Scholar
• Nzabarushimana E, Miousse IR, Shao LJ, Chang JH, Allen AR, Turner J, Stewart B, Raber J, Koturbash I. 2014. Long-term epigenetic effects of exposure to low doses of 56Fe in the mouse lung. J Radiat Res. 55:823–828.
   PubMed Web of Science ®Google Scholar
• Panayiotidis MI, Rancourt RC, Allen CB, Riddle SR, Schneider BK, Ahmad S, White CW. 2004. Hyperoxia-induced DNA damage causes decreased DNA methylation in human lung epithelial-like A549 cells. Antioxid Redox Sign. 6:129–136.
   PubMed Web of Science ®Google Scholar
• Pavillard V, Nicolaou A, Double JA, Phillips RM. 2006. Methionine dependence of tumours: a biochemical strategy for optimizing paclitaxel chemosensitivity in vitro. Biochem Pharmacol. 71:772–778.
   PubMed Web of Science ®Google Scholar
• Pogribny I, Raiche J, Slovack M, Kovalchuk O. 2004. Dose-dependence, sex- and tissue-specificity, and persistence of radiation-induced genomic DNA methylation changes. Biochem Biophys Res Commun. 320:1253–1261.
   PubMed Web of Science ®Google Scholar
• Pogribny I, Koturbash I, Tryndyak V, Hudson D, Stevenson SML, Sedelnikova O, Bonner W, Kovalchuk O. 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. 3:553–561.
   PubMed Web of Science ®Google Scholar
• Portela A, Esteller M. 2010. Epigenetic modifications and human disease. Nat Biotechnol. 28:1057–1068.
   PubMed Web of Science ®Google Scholar
• Prior S, Miousse IR, Nzabarushimana E, Pathak R, Skinner C, Kutanzi KR, Allen AR, Raber J, Tackett AJ, Hauer-Jensen M, et al. 2016. Densely ionizing radiation affects DNA methylation of selective LINE-1 elements. Environ Res. 150:470–481.
   PubMed Web of Science ®Google Scholar
• Qin TC, Si JL, Raynal NJM, Wang XD, Gharibyan V, Ahmed S, Hu X, Jin CL, Lu Y, Shu JM, et al. 2015. Epigenetic synergy between decitabine and platinum derivatives. Clin Epigenet. 7:97. doi: 10.1186/s13148-015-0131-z
   PubMed Web of Science ®Google Scholar
• Qiu H, Yashiro M, Shinto O, Matsuzaki T, Hirakawa K. 2009. DNA methyltransferase inhibitor 5-aza-CdR enhances the radiosensitivity of gastric cancer cells. Cancer Sci. 100:181–188.
   PubMed Web of Science ®Google Scholar
• Rakova I. 1979. [Methylation of newly synthesized DNA in rat bone marrow and thymus after irradiation]. Radiobiologiia 19:413. [in Russian]
   PubMedGoogle Scholar
• Ricketts CJ, Morris MR, Gentle D, Shuib S, Brown M, Clarke N, Wei WB, Nathan P, Latif F, Maher ER. 2013. Methylation profiling and evaluation of demethylating therapy in renal cell carcinoma. Clin Epigenet. 5:16. doi: 10.1186/1868-7083-5-16
   PubMed Web of Science ®Google Scholar
• Rithidech KN, Honikel LM, Reungpathanaphong P, Tungjai M, Jangiam W, Whorton EB. 2015. Late-occurring chromosome aberrations and global DNA methylation in hematopoietic stem/progenitor cells of CBA/CaJ mice exposed to silicon (Si-28) ions. Mutat Res-Fund Mol M. 781:22–31.
   PubMed Web of Science ®Google Scholar
• Rivera AL, Pelloski CE, Gilbert MR, Colman H, De La Cruz C, Sulman EP, Bekele BN, Aldape KD. 2010. MGMT promoter methylation is predictive of response to radiotherapy and prognostic in the absence of adjuvant alkylating chemotherapy for glioblastoma (vol. 12, pg 116, 2010). Neuro-Oncology. 12:617–617.
   Web of Science ®Google Scholar
• Sedelnikova OA, Nakamura A, Kovalchuk O, Koturbash I, Mitchell SA, Marino SA, Brenner DJ, Bonner WM. 2007. DNA double-strand breaks form in bystander cells after microbeam irradiation of three-dimensional human tissue models. Cancer Res. 67:4295–4302.
   PubMed Web of Science ®Google Scholar
• Shivapurkar N, Wilson MJ, Hoover KL, Mikol YB, Creasia D, Poirier LA. 1986. Hepatic DNA methylation and liver-tumor formation in male C3H mice fed methionine-deficient and choline-deficient diets. J Natl Cancer Inst. 77:213–217.
   PubMed Web of Science ®Google Scholar
• Smits KM, Melotte V, Niessen HE, Dubois L, Oberije C, Troost EG, Starmans MH, Boutros PC, Vooijs M, van Engeland M, et al. 2014. Epigenetics in radiotherapy: where are we heading? Radiother Oncol. 111:168–177.
   PubMed Web of Science ®Google Scholar
• Song SH, Han SW, Bang YJ. 2011. Epigenetic-based therapies in cancer: progress to date. Drugs. 71:2391–2403.
   PubMed Web of Science ®Google Scholar
• Song WG, Liu YZ, Liu Y, Zhang C, Yuan B, Zhang LB, Sun SL. 2014. Increased P16 DNA methylation in mouse thymic lymphoma induced by irradiation. PLoS One. 9:e93850.
   PubMed Web of Science ®Google Scholar
• Stein RA. 2012. Epigenetics and environmental exposures. J Epidemiol Community Health. 66:8–13.
   PubMed Web of Science ®Google Scholar
• Strekalova E, Malin D, Good DM, Cryns VL. 2015. Methionine deprivation induces a targetable vulnerability in triple-negative breast cancer cells by enhancing TRAIL receptor-2 expression. Clin Cancer Res. 21:2780–2791.
   PubMed Web of Science ®Google Scholar
• Su SB, Jin YL, Zhang W, Yang LJ, Shen YP, Cao Y, Tong J. 2006. Aberrant promoter methylation of p16(INK4a) and O(6)-methylguanine-DNA methyltransferase genes in workers at a Chinese uranium mine. J Occup Health. 48:261–266.
   PubMed Web of Science ®Google Scholar
• Tawa R, Kimura Y, Komura J, Miyamura Y, Kurishita A, Sasaki MS, Sakurai H, Ono T. 1998. Effects of X-ray irradiation on genomic DNA methylation levels in mouse tissues. J Radiat Res. 39:271–278.
   PubMed Web of Science ®Google Scholar
• Tommasino F, Durante M. 2015. Proton radiobiology. Cancers (Basel). 7:353–381.
   PubMed Web of Science ®Google Scholar
• Wang JZ, Zhang YW, Xu K, Mao XB, Xue LJ, Liu XB, Yu HJ, Chen LB, Chu XY. 2014. Genome-wide screen of DNA methylation changes induced by low dose X-Ray radiation in mice. PLoS One. 9:e90804. doi: 10.1371/journal.pone.0090804
   PubMed Web of Science ®Google Scholar
• Wang Y, Scheiber MN, Neumann C, Calin GA, Zhou DH. 2011. MicroRNA regulation of ionizing radiation-induced premature senescence. Int J Radiat Oncol Biol Phys. 81:839–848.
   PubMed Web of Science ®Google Scholar
• Weil MM, Bedford JS, Bielefeldt-Ohmann H, Ray FA, Genik PC, Ehrhart EJ, Fallgren CM, Hailu F, Battaglia CLR, Charles B, et al. 2009. Incidence of acute myeloid leukemia and hepatocellular carcinoma in mice irradiated with 1 GeV/nucleon Fe-56 ions. Radiat Res. 172:213–219.
   PubMed Web of Science ®Google Scholar
• Weil MM, Ray FA, Genik PC, Yu YJ, McCarthy M, Fallgren CM, Ullrich RL. 2014. Effects of 28Si ions, 56Fe ions, and protons on the induction of murine acute myeloid leukemia and hepatocellular carcinoma. PloS One. 9:e104819.
   PubMed Web of Science ®Google Scholar
• Whitfield BL, Billen D. 1972. In vivo methylation of Escherichia coli DNA following ultraviolet and X-irradiation. J Mol Biol. 63:363–372.
   PubMed Web of Science ®Google Scholar
• Wilson MJ, Shivapurkar N, Poirier LA. 1984. Hypomethylation of hepatic nuclear DNA in rats fed with a carcinogenic methyl-deficient diet. Biochem J. 218:987–990.
   PubMed Web of Science ®Google Scholar
• Ye C, Li LJ. 2014. 5-hydroxymethylcytosine: a new insight into epigenetics in cancer. Cancer Biol Ther. 15:10–15.
   PubMed Web of Science ®Google Scholar