Evaluation of bax, bcl-2, p21 and p53 genes expression variations on cerebellum of BALB/c mice before and after birth under mobile phone radiation exposure

Document Type : Original Article

Authors

1 Department of Medical Physics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

2 Department of Genetics, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

3 Medical Physics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran

4 Department of Anatomy and Cell Biology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

5 Department of Radiation Biology, School of Allied, Tehran University of Medical Sciences, Tehran, Iran

Abstract

Objective(s): The increasing rate of over using cell phones has been considerable in youths and pregnant women. We examined the effect of mobile phones radiation on genes expression variation on cerebellum of BALB/c mice before and after of the birth.
Materials and Methods: In this study, amobile phone jammer, which is an instrument to prevent receiving signals between cellular phonesand base transceiver stations (two frequencies 900 and 1800 MHz) for exposure was used and twelve pregnant mice (BALB/c) divided into two groups (n=6), first group irradiated in pregnancy period (19th day), the second group did not irradiate in pregnancy period. After childbirth, offspring wereclassified into four groups (n=4):Group1: control, Group 2: B1 (Irradiated after birth), Group 3: B2 (Irradiated in pregnancy period and after birth), Group 4: B3 (Irradiated in pregnancy period). When maturity was completed (8-10 weeks old), mice were dissected and cerebellum was isolated. The expression level of bax, bcl-2, p21 and p53 genes examined by real-time reverse transcription polymerase chain reaction (Real-Time RT- PCR).
Results: The data showed that mobile phone radio waves were ineffective on the expression level of bcl-2 and p53 genes) P>0.05(. Also gene expression level of bax decreased and gene expression level of p21 increased comparing to the control group (P<0.05).
Conclusion: From the obtained data it could be concluded that the mobile phone radiations did not induce apoptosis in cells of the cerebellum and the injured cells canbe repaired by cell cycle arrest.

Keywords


1.   Al-Serori H, Kundi M, Ferk F, Mišík M, Nersesyan A, Murbach M, et al. Evaluation of the potential of mobile phone specific electromagnetic fields (UMTS) to produce micronuclei in human glioblastoma cell lines. Toxicol                          In Vitro 2017; 40:264-271.
2.   Liu Y-x, Tai J-l, Li G-q, Zhang Z-w, Xue J-h, Liu H-s, et al. Exposure to 1950-MHz TD-SCDMA electromagnetic fields affect the apoptosis of astrocytes via caspase-3-dependent pathway. PLoS One 2012; 7:e42332.
3.   Yang L, Hao D, Wang M, Zeng Y, Wu S, Zeng Y. Cellular neoplastic transformation induced by 916 MHz microwave radiation. Cell Mol Neurobiol. 2012;32:1039-1046.
4.   Kim K-H, Kabir E, Jahan SA. The use of cell phone and insight into its potential human health impacts. Environ Monit Assess 2016;188:221.
5.   Gil-Garcia A. Output Power-Control Loop Design for GSM Mobile Phones. Agilent Technologies Inc Semiconductor Products Group, Santa Clara, CA, USA. 2003:1-8.
6.   Schaumburg F, Guarnieri F. Assessment of thermal effects in a model of the human head implanted with a wireless active microvalve for the treatment of glaucoma creating a filtering bleb. Phys Med Biol. 2017;62:N191.
7.   Bas O, Odaci E, Kaplan S, Acer N, Ucok K, Colakoglu S. 900 MHz electromagnetic field exposure affects qualitative and quantitative features of hippocampal pyramidal cells in the adult female rat. Brain Res 2009;1265:178-185.
8.   Bourdineaud J-P, Šrut M, Štambuk A, Tkalec M, Brèthes D, Malarić K, et al. Electromagnetic fields at a mobile phone frequency (900 MHz) trigger the onset of general stress response along with DNA modifications in Eisenia fetida earthworms. Arch Ind Hyg Toxicol 2017; 68:142-152.
9.   Greenebaum B. Proceedings of a WHO‐sponsored symposium on “sensitivity to children to EMF exposure”. Bioelectromagnetics. 2005;26(S7):S1-S.
10. Watilliaux A, Edeline J-M, Lévêque P, Jay TM, Mallat M. Effect of exposure to 1,800 MHz electromagnetic fields on heat shock proteins and glial cells in the brain of developing rats. Neurotox Res 2011; 20:109-119.
11. Zhao R, Zhang S, Xu Z, Ju L, Lu D, Yao G. Studying gene expression profile of rat neuron exposed to 1800MHz radio frequency electromagnetic fields with cDNA microassay. Toxicology 2007; 235:167-75.
12. Fine EJ, Ionita CC, Lohr L, editors. The history of the development of the cerebellar examination. Semin Neurol 2002.
13. Wolf U, Rapoport MJ, Schweizer TA. Evaluating the affective component of the cerebellar cognitive affective syndrome. J Neuropsychiatry Clin Neurosci 2008; 21:245-253.
14. Kerr JF, Wyllie AH, Currie AR. Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 1972;26:239.
15. Elmore S. Apoptosis: a review of programmed cell death.Toxicol Pathol 2007; 35:495-516.
16. Brambilla E, Negoescu A, Gazzeri S, Lantuejoul S, Moro D, Brambilla C, Coll JL. Apoptosis-related factors p53, bcl2, and Bax in neuroendocrine lung tumors. Am J Pathol 1996; 149:1941-1952.
17. Gross A. BCL-2 family proteins as regulators of mitochondria metabolism. Biochim Biophys Acta 2016; 1857:1243-1246.
18. Yang J, Liu X, Bhalla K, Kim CN, Ibrado AM, Cai J, Peng TI, Jones DP, Wang X. Prevention of apoptosis by bcl-2: release of cytochrome c from mitochondria blocked. Science 1997;275:1129-1132.
19. Siganak M, Koutsopoulos AV, Neofytou E, Vlachaki E, Psarrou M, Soulitzis N, Pentilas N, Schiza S, Siafakas NM, Tzortzaki EG. Deregulation of apoptosis mediators' p53and bcl2 in lung tissue of COPD patients. Respir Res 2010;11:46.
20. Yilmaz A, Yilmaz N, Serarslan Y, Aras M, Altas M, Özgür T, et al. The effects of mobile phones on apoptosis in cerebral tissue: an experimental study on rats. Genome. 2014; 20:23-27.
21. Liu M-L, Wen J-Q, Fan Y-B. Potential protection of green tea polyphenols against 1800 MHz electromagnetic radiation-induced injury on rat cortical neurons. Neurotox Res 2011; 20:270-276.
22. Karaca E, Durmaz B, Altug H, Yildiz T, Guducu C, Irgi M, et al. The genotoxic effect of radiofrequency waves on mouse brain. J Neurooncol 2012;106:53-58.
23. Zuo H, Lin T, Wang D, Peng R, Wang S, Gao Y, et al. Neural Cell Apoptosis Induced by Microwave Exposure Through Mitochondria-dependent Caspase-3 Pathway. Int J Med Sci 2014; 11:426.
24. Tohidi F, Toosi M, Azimian H, Khademi S, Fardid R, Sarab GA. The gene expression level of p53 and p21 in mouse brain exposed to radiofrequency field. Int J Radiat Res 2015; 13: 337-343.
25. Hardy P, Hedrich H, Bullock G. Gnotobiology and breeding techniques. The laboratory mouse Elsevier Academic Press, London, UK. 2004.
26. Paulraj R, Behari J. Biochemical changes in rat brain exposed to low intensity 9.9 GHz microwave radiation, cell Biochem Biophys 2012; 63: 97-102.
27. Dasdag S, Akdag MZ, Kizil G, Kizil M, Cakir DU, Yokus B. Effect of 900 MHz radio frequency radiation on beta amyloid protein, protein carbonyl, and malondialdehyde in the brain,  Electromagn Biol Med 2012; 31:67-74.
28. Kesari KK, Behari J, Kumar S, Mutagenic response of 2.45 GHz radiation exposure on rat brain, Int J Radiat Biol 2010.
29. Sage C, Burgio E. Electromagnetic Fields, Pulsed Radiofrequency Radiation, and Epigenetics: How Wireless Technologies May Affect Childhood Development. Child Dev 2017.
30. Sage C, Johansson O, Sage SA. Personal digital assistant (PDA) cell phone units produce elevated extremely‐low frequency electromagnetic field emissions. Bioelectromagnetics
2007; 28:386-392.
31. Goldsworthy A. The biological effects of weak electromagnetic fields. Mast-Victims org Forums/Health 2007.
32. MacFarlane M, Williams AC. Apoptosis and disease: a life or death decision. EMBO reports 2004; 5:674-678.
33. Nagata S, Tanaka M. Programmed cell death and the immune system. Nat Rev Immunol 2017;17:333-40.
34. Tsujimoto Y. The role of bcl‐2 family proteins in apoptosis: apoptosomes or mitochondria? Genes to Cells 1998; 3:697-707.
35. Zhao T-Y, Zou S-P, Knapp PE. Exposure to cell phone radiation up-regulates apoptosis genes in primary cultures of neurons and astrocytes. Neurosci Lett 2007; 412:34-38.
36. Yilmaz F, Dasdag S, Akdag MZ, Kilinc N. Whole-body exposure of radiation emitted from 900 MHz mobile phones do not seem to affect the levels of anti-apoptotic bcl-2 protein. Electromagn Biol Med 2008; 27:65-72.
37. Xiong Y, Zhang H, Beach D. D type cyclins associate with multiple protein kinases and the DNA replication and repair factor PCNA. Cell 1992;71:505-514.
38. Kumar V, Abbas AK, Fausto N, Aster JC. Robbins and cotran pathologic basis of disease, Professional Edition: Expert Consult-Online: Elsevier Health Sciences; 2014.
39. Siganaki M, Koutsopoulos AV, Neofytou E, Vlachaki E, Psarrou M, Soulitzis N, et al. Research Deregulation of apoptosis mediators' P53 and bcl2 in lung tissue of COPD patients. threshold 2010;8:11.
40. Dasdag S, Akdag MZ, Ulukaya E, Uzunlar AK, Ocak AR. Effect of mobile phone exposure on apoptotic glial cells and status of oxidative stress in rat brain. Electromagn Biol Med 2009; 28:342-354.
41. Buttiglione M, Roca L, Montemurno E, Vitiello F, Capozzi V, Cibelli G. Radiofrequency radiation (900 MHz) induces Egr‐1 gene expression and affects cell‐cycle control in human neuroblastoma cells. J Cell Physiol 2007; 213:759-767.