Document Type: Original Research

Authors

1 Department of Biochemistry, Shiraz University of Medical Sciences, Shiraz, Iran

2 Department of Radiobiology, School of Paramedical Sciences, Shiraz, Iran

3 Ionizing and Non-ionizing Radiation Protection Research Center (INIRPRC), Shiraz University of Medical Sciences, Shiraz, Iran

4 Department of clinical biochemistry, school of medicine, Shiraz University of Medical Sciences, Shiraz, Iran

5 Professor, School of Paramedical Sciences, Shiraz University of Medical Sciences, Shiraz, Iran

Abstract

Background: Over the past several years, the rapidly increasing use of mobile phones has raised global concerns about the biological effects of exposure to radiofrequency (RF) radiation. Numerous studies have shown that exposure to electromagnetic fields (EMFs) can be associated with effects on the nervous, endocrine, immune, cardiovascular, hematopoietic and ocular systems. In spite of genetic diversity, the onset and progression of cancer can be controlled by epigenetic mechanisms such as gene promoter methylation. There are extensive studies on the epigenetic changes of the tumor suppressor genes as well as the identification of methylation biomarkers in colorectal cancer. Some studies have revealed that genetic changes can be induced by exposure to RF radiation. However, whether or not RF radiation is capable of inducing epigenetic alteration has not been clarified yet. To date, no study has been conducted on the effect of radiation on epigenetic alterations in colorectal cancer (CRC). Several studies have also shown that methylation of estrogen receptor α (ERα), MYOD, MGMT, SFRP2 and P16 play an important role in CRC. It can be hypothesized that RF exposure can be a reason for the high incidence of CRC in Iran. This study aimed to investigate whether epigenetic pattern of ERα is susceptible to RF radiation and if RF radiation can induce radioadaptive response as epigenetic changes after receiving the challenge dose (γ-ray).
Material and Method: 40 male Sprague-Dawley rats were divided into 4 equal groups (Group I: exposure to RF radiation of a GSM cell phone for 4 hours and sacrificed after 24 hours; Group II: RF exposure for 4 hours, exposure to Co-60 gamma radiation (3 Gy) after 24 hours and sacrificed after 72 hrs; Group III: only 3Gy gamma radiation; Group 4: control group). DNA from colon tissues was extracted to evaluate the methylation status by methylation specific PCR.
Results: Our finding showed that exposure to GSM cell phone RF radiation was capable of altering the pattern of ERα gene methylation compared to that of non-exposed controls. Furthermore, no adaptive response phenomenon was induced in the pattern of ERα gene methylation after exposure to the challenging dose of Co-60 γ-rays.
Conclusion: It can be concluded that exposure to RF radiation emitted by GSM mobile phones can lead to epigenetic detrimental changes in ERα promoter methylation pattern.

Keywords

  1. Mortazavi SM, Ahmadi J, Shariati M. Prevalence of subjective poor health symptoms associated with exposure to electromagnetic fields among university students. Bioelectromagnetics. 2007;28:326-30. doi.org/10.1002/bem.20305. PubMed PMID: 17330851.
  2. Mortazavi SMJ, Habib A, Ganj-Karimi AH, Samimi-Doost R, Pour-Abedi A, Babaie A. Alterations in TSH and Thyroid Hormones Following Mobile Phone Use.Oman Med J. 2009; 24(4): 274–278. doi: 10.5001/omj.2009.56. PMCID: PMC3243874.
  3. Agarwal A, Deepinder F, Sharma RK, Ranga G, Li J. Effect of cell phone usage on semen analysis in men attending infertility clinic: an observational study. Fertil Steril. 2008;89(1):124-8. Epub 2007 May 4. PubMed PMID: 17482179.
  4. Cao Y, Tong J. Adaptive response in animals exposed to non-ionizing radiofrequency fields: some underlying mechanisms. Int J Environ Res Public Health. 2014; 11(4):4441-8. doi: 10.3390/ijerph110404441. PubMed PMID: 24758897; PubMed Central PMCID: PMC4025035.
  5. Dimova EG, Bryant PE, Chankova SG. Adaptive response: some underlying mechanisms and open questions. Genetics and Molecular Biology. 2008;31(2):396-408.
  6. Benson VS, Pirie K, Schuz J, Reeves GK, Beral V, Green J. Mobile phone use and risk of brain neoplasms and other cancers: prospective study. Int J Epidemiol. 2013;42:792-802. doi.org/10.1093/ije/dyt072. PubMed PMID: 23657200.
  7. Akan Z, Aksu B, Tulunay A, Bilsel S, Inhan-Garip A. Extremely low-frequency electromagnetic fields affect the immune response of monocyte-derived macrophages to pathogens. Bioelectromagnetics. 2010;31(8):603-12. doi: 10.1002/bem.20607. PubMed PMID: 20809504.
  8. Aydin B, Akar A. Effects of a 900-MHz electromagnetic field on oxidative stress parameters in rat lymphoid organs, polymorphonuclear leukocytes and plasma. Arch Med Res. 2011;42(4):261-7. doi: 10.1016/j.arcmed.2011.06.001. PubMed PMID: 21820603.
  9. Hardell L, Carlberg M, Soderqvist F, Mild KH. Case-control study of the association between malignant brain tumours diagnosed between 2007 and 2009 and mobile and cordless phone use. Int J Oncol. 2013;43:1833-45. doi.org/10.3892/ijo.2013.2111. PubMed PMID: 24064953. PubMed PMCID: 3834325.
  10. Poulsen AH, Friis S, Johansen C, Jensen A, Frei P, Kjaear SK, et al. Mobile phone use and the risk of skin cancer: a nationwide cohort study in Denmark. Am J Epidemiol. 2013;178:190-7. doi.org/10.1093/aje/kws426. PubMed PMID: 23788669.
  11. Elliott P, Toledano MB, Bennett J, Beale L, de Hoogh K, Best N, et al. Mobile phone base stations and early childhood cancers: case-control study. BMJ. 2010;340:c3077. doi.org/10.1136/bmj.c3077. PubMed PMID: 20570865. PubMed PMCID: 3191724.
  12. Kim JG, Park MT, Heo K, Yang KM, Yi JM. Epigenetics meets radiation biology as a new approach in cancer treatment. Int J Mol Sci. 2013;14:15059-73. doi.org/10.3390/ijms140715059. PubMed PMID: 23873297. PubMed PMCID: 3742287.
  13. Nagasaka T, Goel A, Notohara K, Takahata T, Sasamoto H, Uchida T, et al. Methylation pattern of the O6-methylguanine-DNA methyltransferase gene in colon during progressive colorectal tumorigenesis. Int J Cancer. 2008;122:2429-36. doi.org/10.1002/ijc.23398. PubMed PMID: 18240147. PubMed PMCID: 2851179.
  14. Campbell-Thompson M, Lynch IJ, Bhardwaj B. Expression of estrogen receptor (ER) subtypes and ERbeta isoforms in colon cancer. Cancer Res. 2001;61:632-40. PubMed PMID: 11212261.
  15. Gustafsson JA. Estrogen receptor beta--a new dimension in estrogen mechanism of action. J Endocrinol. 1999;163(3):379-83. PubMed PMID: 10588810.
  16. Vladusic EA, Hornby AE, Guerra-Vladusic FK, Lakins J, Lupu R. Expression and regulation of estrogen receptor beta in human breast tumors and cell lines. Oncol Rep. 2000;7(1):157-67. PubMed PMID: 10601611.
  17. Issa JP, Ottaviano YL, Celano P, Hamilton SR, Davidson NE, Baylin SB. Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Nat Genet. 1994;7:536-40. doi.org/10.1038/ng0894-536. PubMed PMID: 7951326.
  18. Tominaga K, Fujii S, Mukawa K, Fujita M, Ichikawa K, Tomita S, et al. Prediction of colorectal neoplasia by quantitative methylation analysis of estrogen receptor gene in nonneoplastic epithelium from patients with ulcerative colitis. Clin Cancer Res. 2005;11:8880-5. doi.org/10.1158/1078-0432.CCR-05-1309. PubMed PMID: 16361578.
  19. Ahuja YR, Sharma S, Bahadur B. Autism: An epigenomic side-effect of excessive exposure to electromagnetic fields. Medicine and Medical Sciences. 2013;5:171-7.
  20. Mortazavi SM, Motamedifar M, Namdari G, Taheri M, Mortazavi AR, Shokrpour N. Non-linear adaptive phenomena which decrease the risk of infection after pre-exposure to radiofrequency radiation. Dose Response. 2013;12(2):233-45. doi: 10.2203/dose-response. PubMed PMID: 24910582; PubMed Central PMCID: PMC4036396.
  21. Mortazavi SMJ, Taeb S, Dehghan N. Alterations of Visual Reaction Time and Short Term Memory in Military Radar Personnel. Iran J Public Health. 2013; 42(4): 428–435. PubMed PMID: 23785684; PMCID: PMC3684731.
  22. Mortazavi SM, Rouintan MS, Taeb S, Dehghan N, Ghaffarpanah AA, Sadeghi Z, Ghafouri F. Human short-term exposure to electromagnetic fields emitted by mobile phones decreases computer-assisted visual reaction time. Acta Neurol Belg. 2012;112(2):171-5. doi: 10.1007/s13760-012-0044-y. PubMed PMID:22426673.
  23. Mortazavi S, Mosleh-Shirazi M, Tavassoli A, Taheri M, Mehdizadeh A, Namazi S, et al. Increased Radioresistance to Lethal Doses of Gamma Rays in Mice and Rats after Exposure to Microwave Radiation Emitted by a GSM Mobile Phone Simulator. Dose Response. 2013;11:281-92. doi.org/10.2203/dose-response.12-010.Mortazavi. PubMed PMID: 23930107. PubMed PMCID: 3682203.
  24. Mortazavi S, Mosleh-Shirazi M, Tavassoli A, Taheri M, Bagheri Z, Ghalandari R, et al . A comparative study on the increased radioresistance to lethal doses of gamma rays after exposure to microwave radiation and oral intake of flaxseed oil. IJRR. 2011; 9(1) :9-14.
  25. Mortazavi SM, Daiee E, Yazdi A, Khiabani K, Kavousi A, Vazirinejad R, Behnejad B, Ghasemi M, Mood MB. Mercury release from dental amalgam restorations after magnetic resonance imaging and following mobile phone use. Pak J Biol Sci. 2008;11(8):1142-6. PubMed PMID: 18819554.
  26. Mortazavi SM, Mahbudi A, Atefi M, Bagheri Sh, Bahaedini N, Besharati A. An old issue and a new look: electromagnetic hypersensitivity caused by radiations emitted by GSM mobile phones. Technol Health Care. 2011;19(6):435-43. doi: 10.3233/THC-2011-0641. PubMed PMID: 22129944.
  27. Mortazavi SMJ, Motamedifar M, Namdari G, Taheri M, Mortazavi AR. Counterbalancing immunosuppression-induced infections during long-term stay of humans in space. J Med Hypotheses and Ideas. 2013;7(1):8-10. doi:10.1016/j.jmhi.2012.12.001
  28. Mortazavi SMJ. Safety Issue of Mobile Phone Base Stations. J biomed physics & engineering. 2013;3(1):1-2.
  29. Mortazavi SMJ. Adaptive responses after exposure to cosmic and natural terrestrial radiation. Indian J Rad Res. 2004;1(1):104-12.
  30. Mortazavi SMJ, Tavassoli A, Ranjbari F, Moammaiee P. Effects of laptop computers’ electromagnetic field on sperm quality. Journal of Reproduction & Infertility. 2011;11(4):251-8.
  31. Mortazavi SM, Vazife-Doost S, Yaghooti M, Mehdizadeh S, Rajaie-Far A. Occupational exposure of dentists to electromagnetic fields produced by magnetostrictive cavitrons alters the serum cortisol level. J Nat Sci Biol Med. 2012;3(1):60-4. doi: 10.4103/0976-9668.95958. PubMed PMID: 22690053; PubMed Central PMCID: PMC3361780.
  32. In: FC News (Federal Communications Commission). Document: Enforcement bureau steps up education and enforcement efforts against cellphone and GPS jamming. [February 9, 2011]. Available from: https://transition.fcc.gov/eb/News_Releases/DOC-304575A1.html.
  33. Mortazavi SM, Neghab M, Anoosheh SM, Bahaeddini N, Mortazavi G, Neghab P, Rajaeifard A. High-field MRI and mercury release from dental amalgam fillings. Int J Occup Environ Med. 2014;5(2):101-5. PubMed PMID: 24748001.
  34. Mokarram P, Zamani M, Kavousipour S, Naghibalhossaini F, Irajie C, Moradi Sarabi M, et al. Different patterns of DNA methylation of the two distinct O6-methylguanine-DNA methyltransferase (O6-MGMT) promoter regions in colorectal cancer. Mol Biol Rep. 2013;40:3851-7. doi.org/10.1007/s11033-012-2465-3. PubMed PMID: 23271133.
  35. Agrawal A, Murphy RF, Agrawal DK. DNA methylation in breast and colorectal cancers. Mod Pathol. 2007;20:711-21. doi.org/10.1038/modpathol.3800822. PubMed PMID: 17464311.
  36. Nagaraju GP, El-Rayes BF. SPARC and DNA methylation: possible diagnostic and therapeutic implications in gastrointestinal cancers. Cancer Lett. 2013;328:10-7. doi.org/10.1016/j.canlet.2012.08.028. PubMed PMID: 22939997.
  37. Harder J, Engelstaedter V, Usadel H, Lassmann S, Werner M, Baier P, et al. CpG-island methylation of the ER promoter in colorectal cancer: analysis of micrometastases in lymph nodes from UICC stage I and II patients. Br J Cancer. 2009;100:360-5. doi.org/10.1038/sj.bjc.6604859. PubMed PMID: 19142184. PubMed PMCID: 2634714.
  38. Antwih DA, Gabbara KM, Lancaster WD, Ruden DM, Zielske SP. Radiation-induced epigenetic DNA methylation modification of radiation-response pathways. Epigenetics. 2013;8(8):839-48. doi: 10.4161/epi.25498. PubMed PMID: 23880508; PubMed Central PMCID: PMC3883787.
  39. Ye S, Yuan D, Xie Y, Pan Y, Shao C. Role of DNA methylation in the adaptive responses induced in a human B lymphoblast cell line by long-term low-dose exposures to gamma-rays and cadmium. Mutat Res Genet Toxicol Environ Mutagen. 2014;773:34-8. doi.org/10.1016/j.mrgentox.2014.08.004. PubMed PMID: 25308704.