Other Studies - Free Oxygen Radicals

A free radical is a molecule or ion that has an unpaired electron in its outer orbit. Radical particles are unstable and are very reactive. Most commonly free radicals are produced from oxygen metabolism, and are called reactive oxygen species (ROS) (Yurekli, 2006). Cells stressed by oxidation react by producing ROS. Chain reactions can start as the unpaired electron is transferred from one molecule to another. Various consequences can arise, one of which is lipid peroxidation. One of the markers of this is the production of malondialdehyde (MDA).

Based on oxidant products, 3 main classes of prooxidant enzymes can be designated: (1) nitric oxide symthases (NOS) produce nitric oxide (NO); (2) cyclooxygenases (COX), xanthine oxidase (XO) and NADPH oxidase generate superoxide anion as the main oxidant in various cell types; (3) myeloperoxidase (MAO) and monoamine oxidase generate hypochlorous acid and hydrogen peroxide in leukocytes and in parenchymal cells respectively. Some enzymatic systems can counterbalance the production of ROS. These include superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) (Irmak, 2002). ). Balance between the prooxidants and the antioxidant enzymes can be upset by an increase in free radicals or by a decrease in antioxidants.

Some research studies have explored this area. Moustafa (2001) reported an increase in plasma lipid peroxide and a decrease in erythrocyte antioxidants in humans exposed to a 900 MHz field for up to 4 hours. However, there are no details of SAR levels, and there was no sham exposure. Dasdag (2004) found that MDA levels were increased in the brains of rats exposed to RFR from a 900 MHz source at SAR of 0.52 W/kg for 20 minutes a day, 7 days a week, for 1 month. However, there was no histological alteration or change in brain phospholipid fatty acid composition. Irmak (2002) did not find any changes in oxidant or antioxidant levels in brains of rabbits exposed to RFR at 900 MHz for 30 minutes per day for 1 week. Serum SOD levels were increased and serum NO levels decreased. Ilhan (2004) exposed rats to RFR at 900 MHz for 1 hour a day for 1 week. They found increased MDA and NO levels in brain tissue, decrease in SOD and GSH-Px levels, and increase in XO and adenosine deaminase levels. These changes were prevented when the rats were treated with Ginkgo biloba, which has antioxidant activity. Zmyslony and colleagues (2004) found that ROS levels were increased in rat lymphocytes exposed to RFR at 930 MHz (SAR 1.5 W/kg) for either 5 or 15 minutes. The lymphocytes had been treated in vitro with FeCl2 to induce oxidated stress. Ozguner (2005) reported that antioxidant enzyme levels were reduced and levels of ROS increased in the kidneys of rats exposed to 900 MHz frequency RFR for 30 minutes a day for 1 month. The whole body SAR was 4 W/kg. Yurekli (2006) reported that in rats exposed to far-field exposure (power density 3.67 W/m², SAR 11.3 mW/kg) for 8 days and 7 hours a day, MDA and SOD levels increased and glutathione levels decreased. However, there were baseline differences in mean weight between the exposed and the sham rats, and the experiment does not appear to have been a randomized, double-blind study. Meral (2007) found increased levels of MDA and decreased levels of CAT and GSH in brain tissue of guinea pigs exposed to GSM RFR at 890-915 MHz for 12 h/day for 30 days. Blood levels of MDA, vitamins A, D3, and E, and CAT increased, and GSH decreased. Friedman (2007) reported that exposure of rat or HeLa cells to RFR at 835 MHz was associated with activation of extracellular-signal-regulated kinase (ERK), which results from initial activation of NADH oxidase, leading to generation of ROS, and then to the activation of the ERK cascade. Arthur (2007) reviews Friedman's paper in an accompanying commentary.

There have been a number of negative studies in this area. Hook et al. (2005) reported no evidence of oxidative stress in mouse macrophage cells exposed to RFR at either 835.62 MHz (FMCW) or 847.74 MHz (CDMA) at a SAR of 0.8 W/kg for 20-22 hours. Lantow (2006a) also found no significant difference in production of free radicals after exposure of human leukemia cells to RFR at 1800 MHz at SARs of 0.5-2.0 W/kg for 45 minutes. The same group (Lantow 2006b) did not find induction of ROS release (or of HSP70 expression) in human lymphocytes or monocytes with RF exposure at SAR of 2W/kg for 45 minutes. However, they did find a decrease in ROS production in monocytes during sham exposure when GSM-DTX exposure was being tested. The reason for this is not clear. Simko (2006) reported no increase in free radicals after exposure of human monocytes to RFR at 1800 MHz for 60 minutes. Ferreira (2006) did not find any evidence of lipid or protein oxidative damage in the brains of rats exposed to 834 MHz frequency RFR at SAR of 0.98 W/kg for 6 days, 7 and 1/2 hours a day.

Authors
Arthur JSC (2007)
Title
MAPK activation by radio waves.
Journal
Biochem J 405, e5-6.


Authors

Dasdag S, Akdag MZ, Aksen F, Bashan M, et al. (2004).
Title
Does 900 MHz GSM mobile phone exposure affect rat brain?
Journal
Electromagnetic Biology and Medicine 23:201-214.
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Authors

Ferreira AR, Bonatto F, Pasquali MA, Polydoro M, et al. (2006)
Title
Oxidative stress effects on the central nervous system of rats after acute exposure to ultra high frequency electromagnetic fields.
Journal
Bioelectromagnetics 27:487-493.
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Authors
Friedman J, Kraus S, Hauptman Y, Schiff Y, et al. (2007)
Title
Mechanism of short-term ERK activation by electromagnetic fields at mobile phone frequencies
Journal
Biochem J 405:559-568.
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Authors
Guney M, Ozguner F, Oral B, Karahan N, Mungan T. (2007)
Title
900 MHz radiofrequency-induced histopathologic changes and oxidative stress in rat endometrium: protection by vitamins E and C.
Journal
Toxicol Ind Health 23(7): 411-420.

Authors
Ayata A, Mollaoglu H, Yilmaz HR, Akturk O, et al. (2004)
Title
Oxidative stress-mediated skin damage in an experimental mobile phone model can be prevented by melatonin.
Journal
J Dermatol 31:878-883.
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Authors
Hook GJ, Spitz DR, Sim JE, Higashikubo R, Baty JD, et al. (2005)
Title
Evaluation of parameters of oxidative stress after in vitro exposure to FMCW- and CDMA- modulated radiofrequency radiation fields.
Journal
Radiat Res 163:497-504.
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Authors
Höytö A, Luukkonen J, Juutilainen J, Naarala J. (2008)
Title
Proliferation, Oxidative Stress and Cell Death in Cells Exposed to 872 MHz Radiofrequency Radiation and Oxidants.
Journal
Radiat Res. 170(2):235-243.

Authors
Ilhan A, Gurel A, Armutcu F, Kamisli S, et al. (2004)
Title
Ginkgo biloba prevents mobile phone-induced oxidative stress in rat brain.
Journal
Clinica Chemica Acta 340:153-162.
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Authors
Irmak K, Fadillioglu E, Gulec M, Erdogan H, et al. (2002)
Title
Effects of electromagnetic radiation from a cellular telephone on the oxidant and antioxidant levels in rabbits.
Journal
Cell Biochem Funct 279-283.
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Authors
Koyu A, Ozguner F, Yilmaz H, Uz E, Cesur G, Ozcelik N.
Title
The protective effect of caffeic acid phenethyl ester (CAPE) on oxidative stress in rat liver exposed to the 900 MHz electromagnetic field.
Journal
Toxicol Ind Health. 2009. 25(6):429-434.

Authors
Lantow M, Schuderer J, Hartwig C, Simko M (2006):
Title
Free radical release and HSP70 expression on two human immune-relevant cell lines after exposure to 1800 MHz radiofrequency radiation.
Journal
Radiation Research 165:88-94
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Authors
Lantow M, Lupke M, Frahm J, Mattson MO, et al. (2006b):
Title
ROS release and Hsp70 expression after exposure to 1,800 MHz radiofrequency electromagnetic fields in primary human monocytes and lymphocytes.
Journal
Radiat Environ Biophys 45:55-62.
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Authors
Luukkonen J, Hakulinen P, Mäki-Paakkanen J, Juutilainen J, Naarala J.
Title
Enhancement of chemically induced reactive oxygen species production and DNA damage in human SH-SY5Y neuroblastoma cells by 872 MHz radiofrequency radiation.
Journal
Mutat Res 24 Dec 2008 Ahead of print.

Authors
Luukkonen J, Juutilainen J, Naarala J.
Title
Combined effects of 872 MHz radiofrequency radiation and ferrous chloride on reactive oxygen species production and DNA damage in human SH-SY5Y neuroblastoma cells.
Journal
Bioelectromagnetics April 28, 2010 Ahead of print.

Authors
Meral I, Mert H, Mert N, Deger Y, et al. (2007):
Title
Effects of 900 MHz electromagnetic field emitted from cellular phone on brain oxidative stress and some vitamin levels.
Journal
Brain Res doi:10.1016/j.brainres.2007.07.015
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Authors

Moustafa YM, Moustafa RM, Belacy A, Abou-EL-Ela SH, et al. (2001):
Title
Effects of acute exposure to the radiofrequency fields of cellular phones on plasma lipid peroxide and antioxidase activities in human erythrocytes.
Journal
J Pharm Biomed Anal 26:605-8.
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Authors

Ozguner F, Oktem F, Ayata A, Koyu A, et al. (2005)
Title
A novel antioxidant agent caffeic acid phenetyl ester prevents long-term mobile phone exposure-induced renal impairment in the rat.
Journal
Mol Cell Biochem 277:73-80.
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Authors
Ozgur E, Güler G, Seyhan N.
Title
Mobile phone radiation-induced free radical damage in the liver is inhibited by the antioxidants n-acetyl cysteine and epigallocatechin-gallate.
Journal
Int J Radiat Biol. Sep 1, 2010. Ahead of print.

Authors
Simko M, Hartwig C, Lantow M, Lupke M, et al. (2006):
Title
Hsp70 expression and free radical release after exposure to non-thermal radio-frequency electromagnetic fields and ultrafine particles in human Mono Mac 6 cells.
Journal
Toxicology Letters 161:73-82.
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Authors
Tomruk A, Guler G, Dincel AS.
Title
The Influence of 1800 MHz GSM-like Signals on Hepatic Oxidative DNA and Lipid Damage in Nonpregnant, Pregnant, and Newly born Rabbits.
Journal  
Cell Biochem Biophys. Oct 23, 2009. Ahead of print.

Authors

Yurekli AI, Ozkan M, Kalkan T, Saybasili H, et al. (2006)
Title
GSM base station electromagnetic radiation and oxidatice stress in rats.
Journal
Electromagnetic Biology and Medicine 25:177-188.
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Authors
Zeni O, Di Pietro R, d'Ambrosio G, Massa R, et al. (2007)
Title
Formation of reactive oxygen species in L929 cells after exposure to 900 MHz RF radiation with and without co-exposure to 3'chloro-4- (dichloromethyl)-5-hydroxy-2(5H)-furanone.
Journal
Radiation Research 167:306-311.
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Authors

Zmyslony M, Politanski P, Rajkowska E, Szymczak W, et al. (2004)
Title
Acute exposure to 930 MHz CW electromagnetic radiation in vitro affects reactive oxygen species level in rat lymphocytes treated by iron ions
Journal
Bioelectromagnetics 25:324-328
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