Itali: Overzicht gecombineerde effecten van EMV en andere chemische of fysische stoffen.

zondag, 17 juli 2011 - Categorie: Onderzoeken




In this paper the most significant in vitro studies involving combined exposures to electromagnetic fields, both extremely low frequencies and radiofrequencies, and chemical or physical agents are presented and discussed.

Due to the increasing use of electromagnetic fields and the large diffusion of environmental pollution, it may be questionable whether combined exposures to such agents could induce cooperative effects on living organisms which, in the real life situation, are exposed every day to more than one chemical and/or physical
environmental agent. Moreover, it is likely that combined action of different agents is involved in carcinogenesis 1 and several investigators have focused on the possibility that electromagnetic radiation could enhance the effects of carcinogens 2.

In this paper the most significant in vitro studies related to combined exposures at both extremely low frequencies (ELF) and radiofrequencies (RF) with chemical or physical agents are presented and discussed. Most of them refer to co-exposures of mammalian cells (primary cultures and mammalian cell lines) and the biological effects mainly investigated include genotoxicity, as well as cell transformation and cancer-relevant nongenotoxic effects such as apoptosis, cell proliferation, cell cycle, intercellular communication, oxidative stress.

Effects of co-exposures to ELF magnetic fields
Data reported in the literature on the effects of combined exposures to ELF magnetic fields (MF) has been reviewed by Juutilainen and co-workers in 2006 3. The authors examined 65 papers dealing with in vitro studies and short-term animal studies relevant to cancer that have been published in peer reviewed journals between 1986 and 2002. This quantitative analysis showed that in 61% of the in vitro investigations an interaction between ELF MF and other chemical and physical treatments occurred. In the large majority of the studies MF exposure increased the effect induced by other treatments, but the suppression of some responses was also reported. In most of these studies magnetic fields of 100 ?T or higher were employed. Apoptosis resulted the most susceptible parameter to co-exposures. The authors suggested that the radical pair mechanism could explain combined effects of magnetic fields with agents inducing free radical production and the nonlinear dependency on magnetic field strength 3.

The results published from 2002 to 2008 have been reviewed in the framework of the EMF-NET (Effects of exposure to electromagnetic fields: from science to public health and safer workplace) project of the 6th Framework Research Programme of the European Union 4. They also confirm the ability of magnetic fields in cooperating with chemical or physical agents and apoptosis and DNA damage as the most susceptible
parameters. In particular, a decrease in apoptosis induced by co-exposures to temperature 5, camptothecin 6 and X Ray 7 has been reported as well as an increase induced by vinblastine 8 or photodynamic therapy 9.

Our research unit also detected a decrease in apoptosis, either spontaneous and induced by anti-FAS, in Jurkat cells exposed to a 50 Hz (1mT) intermittent magnetic field 10. Villarini et al. 11 reported increased or decreased single strand breaks (SSBs) in lymphocytes exposed to 50 Hz (3 mT) on the bases of the xenobiotics employed for co-exposures. Similar results have been also obtained by using benzene and its metabolites 12 or X ray 13.

Recently, other authors have shown the ability of magnetic fields to interact with other chemical or M.R. SCARF physical agents. In particular, enhancement in chemically-induced DNA damage was reported after ELF-MF exposure 14, 15 as well as hydrogen peroxide-induced Reactive Oxygen Species (ROS) production 15.
Other authors reported that pre-exposures of L929 cells to 50 Hz, 100 ?T MF decreased apoptosis induced by Menadione but had no effects on UVB exposed cells 16.

Opposite results were found by Jian et al, who found that ELF-MF enhanced X-ray-induced apoptosis 17.

Effects of co-exposures to Radiofrequency Radiation
The number of papers concerning the evaluation of cooperative effects induced by combined exposures to RF radiation and chemical or physical agents is minor than those available for ELF fields. In addition, apart from the variety of experimental details investigated in terms of cell types and co-exposure agents employed, RF-radiation exposures of different characteristics have been tested, such as frequency (from 800 to 2000 MHz), Specific Absorption Rate (SAR) values (from 0.4 to 28 W/kg) and signals (continuous wave, GSM modulation, UMTS modulation). However, this topic has been addressed by several research groups and both positive and negative findings have been reported. The possible induction of genotoxic effects and effects on cell-redox status are the most investigated issues.

Concerning DNA damage, about ten paper have been published in the last years and most of them have been reviewed in 18. Even if about half of them does not report effects, the other indicate that cooperative effects can not be excluded, suggesting the possibility of an increased risk of genetic damage due to combined exposures.

Similar considerations can be made on the influence of RF field co-exposures on cell redox status. About nine studies have evaluated combined effects of RF fields with chemicals inducing oxidative stress. Three of them show a significant increase in ROS levels produced by FeCl2 19 and menadione 20 or in lipid peroxidation induced by tert-butylhydroperoxide 21. The remaining papers reported lack of cooperative effects

In this paper a short review of the studies published in peer reviewed journals related to the biological effects of combined exposures to non ionising electromagnetic fields and environmental pollutants is presented. The data reported on both ELF and RF fields suggest that cooperative effects can not be excluded. This observation deserves further studies to better understand the induction of biological effects after combined exposures to electromagnetic fields and physical or chemical agents.

1 W. Burkart and T. Jung. Health risks from combined exposures: mechanistic considerations on deviations
from additivity. Mutat. Res. 411: 119128 (1998).

2 J. Juutilainen and S. Lang. Genotoxic carcinogenic and teratogenic effects of electromagnetic fields.
Introduction and overview. Mutat. Res. 387: 165-171 (1997).

3 J. Juutilainen, T. Kumlin and J. Naarala. Do extremely low frequency magnetic fields enhance the effects of
environmental carcinogens? A meta-analysis of experimental studies. Int. J. Radiat. Biol. 82: 1-12 (2006).

4 EMF-NET: Report on laboratory studies on ELF fields. 2008.

5 J.G. Robison, A.R. Pendleton, K.O. Monson, B.K. Murray, K.L. ONeill. Decreased DNA repair rates and
protection from heat induced apoptosis mediated by electromagnetic field exposure. Bioelectromagnetics 23:
106-112 (2002).

6 M.C. Pirozzoli, C. Marino, G.A. Lovisolo, C. Laconi, L. Mosiello , A. Neuroni.. Effects of 50 Hz
electromagnetic field exposure on apoptosis and differentiation in a neuroblastoma cell line.
Bioelectromagnetics. 24: 510-516 (2003).

7 F. Tian, T. Nakahara, M. Yoshida, N. Honda, H. Hirose, J. Miyakoshi. Exposure to Power Frequency
Magnetic Fields Suppresses X-Ray-Induced Apoptosis Transiently in Ku80-Deficient xrs5 Cells. Biochem
Biophys Res Commun 292: 355361 (2002).

8 G.R. Verheyen, G. Pauwels, L. Verschaeve, G. Schoeters. Effect of co-exposure to 50 Hz magnetic fields and
an aneugen on human lymphocytes, determined by the cytokinesis block micronucleus assay.
Bioelectromagnetics 24: 160-164 (2003).

9 M. Ravera, H. Berg. Differences in lethality between cancer cells and human lymphocytes caused by LFelectromagnetic
fields. Bioelectromagnetics. 25: 503-507 (2004).

10 R. Palumbo, D. Capasso, F. Brescia, P. Mita, M. Sarti, F. Bersani, M.R. Scarfi. Effects on apoptosis and
reactive oxygen species formation by Jurkat cells exposed to 50 Hz electromagnetic fields. Bioelectromagnetics
27: 159-162 (2006).

11 M. Villarini, M. Moretti, G. Scassellati-Sforzolini, B. Boccioli, R. Pasquini. Effects of co-exposure to
extremely low frequency (50 Hz) magnetic fields and xenobiotics determined in vitro by the alkaline comet
assay. Sci Total Environ 361: 208-219 (2006).

12 M. Moretti, M. Villarini, S. Simonucci, C. Fatigoni, G. Scassellati-Sforzolini, S. Monarca, R. Pasquini, M.
Angelucci, M. Strappini. Effects of co-exposure to extremely low frequency (ELF) magnetic fields and benzene
or benzene metabolites determined in vitro by the alkaline comet assay. Toxicology Letters 157: 119128 (2005).

13 G.R. Ding, T. Nakahara, J. Miyakoshi. Induction of kinetochore-positive and kinetochore-negative
micronuclei in CHO cells by ELF magnetic fields and/or X-rays. Mutagenesis. 18: 439-443 (2003).

14 S. Koyama, T. Sakurai, T. Nakahara, J. Miyakoshi. Extremely low frequency (ELF) magnetic fields
enhance chemically induced formation of apurinic/apyrimidinic (AP) sites in A172 cells. Int. J. Radiat Biol, 84:
53-59 (2008).

15 S. Falone, M.R. Grossi, B. Cinque, B. D'Angelo, E. Tettamanti, A. Cimini, C. Di Ilio, F. Amicarelli. Fifty
hertz extremely low-frequency electromagnetic field causes changes in redox and differentiative status in
neuroblastoma cells. The Int. J. of Biochem. & Cell Biol. 39: 2093-2106 (2007).

16 A. Markkanen, J. Juutilainen, J. Naarala. Pre-exposure to 50 Hz magnetic fields modifies menadioneinduced
DNA damage response in murine L929 cells. Int J Radiat Biol. 84: 742-51 (2008).

17 W. Jian, Z. Wei, C. Zhiqiang, F. Zheng. X-Ray-Induced Apoptosis of BEL-7402 Cell Line Enhanced by
Extremely Low Frequency Electromagnetic Field In Vitro. Bioelectromagnetics 30: 163-165 (2009)

18 Vijayalaxmi and T.J. Prihoda. Genetic damage in mammalian somatic cells exposed to radiofrequency
radiation: A meta-analysis of data from 63 publications (19902005). Radiat. Res. 169: 561574 (2008).

19 M. Zmyslony, P. Politanski, E. Rajkowska, W. Szymczak and J. Jajte, Acute exposure to 930 MHz CW
electromagnetic radiation in vitro affects reactive oxygen species level in rat lymphocytes treated by iron ions.
Bioelectromagnetics 25, 324328 (2004).

20 J. Luukkonen, P. Hakulinen, J. Mki-Paakkanen, J. Juutilainen, J. Naarala. Enhancement of chemically
induced reactive oxygen species production and DNA damage in human SH-SY5Y neuroblastoma cells by 872
MHz radiofrequency radiation. Mutat. Res. 662: 54-58 (2009).

21 A. Hoyto, J. Luukkonen, J. Juutilainen, J. Naarala. Proliferation, oxidative stress, and cell death in cells
exposed to 872 MHz radiofrequency radiation and oxidants. Radiat Res 170: 235243 (2008).

22 G. J. Hook, D. R. Spitz, J. E. Sim, R. Higashikubo, J. D. Baty, E. G. Moros and J. L. Roti Roti, Evaluation
pf parameters of oxidative stress after in vitro exposure to FMCW- and CDMA-modulated radiofrequency
radiation fields. Radiat. Res. 162: 497504 (2004).

23 M. Simko, C. Hartwig, M. Lantow, M. Lupke, M. O. Mattsson, Q. Rahman and J. Rollwitz, Hsp70
expression and free radical release after exposure to non-thermal radio-frequency electromagnetic fields and
ultrafine particles in human Mono Mac 6 cells. Toxicol Lett. 161: 7382 (2006).

24 M. Lantow, J. Schuderer, C. Hartwig and M. Simko, Free radical release and HSP70 expression in two
human immune-relevant cell lines after exposure to 1800 MHz radiofrequency radiation. Radiat. Res. 165: 88
94 (2006).

25 O. Zeni, R. Di Pietro, G. dAmbrosio, R. Massa, M. Capri, J. Naarala, J. Juutilainen, M.R. Scarf. Kinetics
of reactive oxygen species formation in L929 cell cultures following exposure and co-exposure to RF radiation
(900 MHz) and 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX). Radiat Res 167: 306311 (2007).

26 F. Brescia, M. Sarti, R. Massa, ML. Calabrese, A. Sannino, MR. Scarf (2009) ROS formation is not
enhanced by exposure to UMTS 1950 MHz radiation and co-exposure to ferrous ions in Jurkat cells.
Bioelectroagnetics 30, 525-535.

27 J. Luukkonen, J. Juutilainen, J. Naarala. Combined effects of 872 MHz radiofrequency radiation and ferrous
chloride on reactive oxygen species production and DNA damage in human SH-SY5Y neuroblastoma cells.
Bioelectroagnetics DOI 10.1002/bem.20580 (2010

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