5. A possible mechanism of carcinogenesis

Cellphone radiation can alter c-fos and c-jun proto-oncogene activity, and both these gene products have been implicated in the activation of cell death signal transduction pathways [48, 49].

DNA damage including micronucleus formation, chromosomal aberrations, and DNA strand breaks has been reported in human cells in response to microwave radiation. Certain kinds of DNA damage like aneuploidy can result in cell cycle arrest and activation of apoptosis. Double-strand breaks in DNA caused by radiation can also signal apoptosis.

damage can result in p53-mediated postmitotic apoptosis in human cells [42]. EMR from cell base stations has also been reported to increase the frequency of DNA strand breaks in the lympho-

Cellphone radiation can increase c-fos proto-oncogene activity by more than 40% in embryonic mouse cells and alter c-jun proto-oncogene activity in rat cells [45, 46]. However, there is some conflicting data on this subject, and reports can be inconsistent, while data in humans appear to be lacking. Additionally, there is no evidence to suggest that microwaves can cause point mutations, which are associated with oncogene activation in humans and other mammals [47]. Nevertheless, the c-fos protein can induce cellular apoptosis, and the c-jun gene product has been found to be necessary for neuronal apoptosis in human and other mammalian cells [48, 49]. Microwaves can affect chromatin conformation and histone phosphorylation in human lymphocytes, as well, which may be associated with epigenetic mechanisms at the cellular level [50]. A significant increase in the efflux of calcium ions has been observed in human neuroblastoma cells at extremely low levels of microwave radiation indicating a high degree of sensitivity [51]. This cellular calcium imbalance may reflect the release of calcium ions from internal organelles like mitochondria and the endoplasmic reticulum [ER] as occurs in response to certain heavy metals, and this process is linked to an apoptotic pathway [11].

Microwaves have been reported to induce ERK-mediated apoptosis and cell cycle arrest in a dose-dependent manner in a human natural killer cell line (NK-92) just 1 hour after exposure, which could lead to general immune suppression and the development of tumors [13]. Activation of the Ras/Raf/ERK pathway has been associated with both the intrinsic mitochondrial and the extrinsic death receptor apoptotic pathways [52]. Continuous microwave irradiation (2.45 GHz) can cause Fas-induced apoptosis via the extrinsic death receptor pathway in a human Jurkat T-cell line [14]. Fas is a member of the tumor necrosis factor receptor (TNFR)/ nerve growth receptor (NGR) family. In another recent study, microwave radiation exposure from a GSM cellphone simulator (900 MHz) also resulted in a significant increase in the apoptotic rate of a human T-cell line (Jurkat cells) [53]. In addition, the formation of ROS in normal human peripheral blood mononuclear cells can stimulate apoptosis in response to 900 MHz cellphone radiation. In this case, apoptosis is induced via the mitochondrial pathway and is mediated by ROS [54]. Finally, apoptosis can be stimulated in human brain glioblastoma cells directly in response to microwaves. EMR exposure in the cell base station frequency range [1800 MHz] induces apoptosis-related events such as ROS bursts and oxidative DNA damage, which in turn promote p53-dependent caspase-3 activation through release of cytochrome c

Cellphone radiation can alter c-fos and c-jun proto-oncogene activity, and both these gene products have been implicated in the activation of cell death signal transduction pathways [48, 49].

DNA damage including micronucleus formation, chromosomal aberrations, and DNA strand breaks has been reported in human cells in response to microwave radiation. Certain kinds of

from mitochondria [12].

5. A possible mechanism of carcinogenesis

cytes of cellphone users and in individuals residing near cell base stations [43, 44].

142 Current Understanding of Apoptosis - Programmed Cell Death

The generation of reactive oxygen species in response to microwave radiation has been observed in various studies. Certain carcinogens like UV rays exert some of their carcinogenic effects via the generation of reactive oxygen species in the cell [55]. This is true of X-rays, as well [56]. Certain oncogenic proteins such as Ras also produce elevations in ROS upon stimulation. Many genes and proteins that respond to conditions of oxidative stress within the cell subsequently trigger apoptosis. Because mitochondria are important regulators of cellular redox status, the induction of oxidative stress exhibits its effects upon these organelles to trigger the intrinsic apoptotic pathway via cytochrome c release and caspase cascade activation [57, 58].

Moreover, an increase in the efflux of calcium ions has been observed in human neuroblastoma cells at extremely low levels of microwave radiation, and this cellular calcium imbalance may reflect the release of calcium ions from internal organelles. In this regard, lead perturbs and alters the release of intracellular calcium stores from organelles like the endoplasmic reticulum (ER) and mitochondria [59, 60]. Mitochondria can accumulate large amounts of calcium, for example, in the presence of inorganic phosphate. The rise in calcium results in an upregulation of energy metabolism and an increase in mitochondrial membrane potential. Then, the release of this accumulated calcium through a special channel, permeability transition pore (PTP), can cause mitochondrial depolarization. According to the model of glutamate toxicity, mitochondrial calcium accumulation and resultant membrane depolarization are clearly linked to the initiation of a cell death pathway in mitochondria [61, 62].

Microwaves can also affect chromatin conformation and histone phosphorylation in human lymphocytes. Interestingly, in addition to causing genetic damage via oxidative and nonoxidative mechanisms (DNA adducts), certain carcinogenic heavy metals can cause significant epigenetic changes in cells such as DNA methylation and histone modifications. These can result in gene silencing or reactivation of gene expression [63]. MicroRNAs (miRNAs) are highly conserved, noncoding small RNAs regulating the expression of broad gene networks at the posttranscriptional level and may represent another epigenetic control mechanism. In many cases, the specific effects of such epigenetic changes still appear to be unknown and could conceivably impact major cellular functions like cell death and/or proliferation [64].

Apoptosis is involved in maintaining cell number in tissues, and, although increased cell proliferation is necessary, it is not sufficient for cell transformation to take place. Normally, in multicellular organisms, a dynamic balance exists between cell birth and cell death to retain constant cell numbers throughout adult life. This homeostasis depends on an integrated balance between apoptosis (cell death) and mitosis (cell division) such that these two activities are counterbalanced and equivalent. In fact, this homeostatic balance may contribute a critical defense mechanism of the cell to various genotoxic agents such as carcinogens [65].

A permanent loss in homeostatic equilibrium between cell division and cell death may be a critical determinant in the transition to tumorigenesis. The increased proliferation in preneoplastic lesions is often accompanied by a parallel increase in cell death, at least in the initial stages of transformation to cancer. Quantitative histological studies in the rat liver model have revealed that the rate of apoptosis tends to increase from normal to preneoplastic to malignant cells [66]. Comparative studies with the rat bladder have also suggested that apoptosis is closely linked to chemically induced carcinogenesis [67]. Additional support for this transition comes from a variety of other models [7]. However, ultimately, tumor formation only seems to occur once the cancer cells have become resistant to apoptosis while continuing to proliferate. In fact, acquired resistance to apoptosis appears to be a pivotal event in cell immortalization and the transition to malignancy [65].

parameter definitively since significant biochemical differences can exist between transformed and non-transformed cells. Blood cells of children should also specifically be tested since they are susceptible to leukemia from high power voltage (HPV) lines, which emit low-frequency radio waves. The developing tissues of children have already been found to be more susceptible to the penetration of cellphone radiation. According to a new approach to cancer risk assessment, if apoptosis is induced in these normal tissues from adults and children, along with the epidemiological data, this would be sufficient criteria to establish cellphone tower EMR as a complete carcinogen providing that microwave exposure is at a high enough specific

Electromagnetic Radiation from Cellphone Towers: A Potential Health Hazard for Birds, Bees, and Humans

http://dx.doi.org/10.5772/intechopen.76084

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As an example, sufficiently high SAR levels for microwave radiation are likely to be achieved only very close to or directly in front of cellular antennas mounted on a roof, whereas a distance of up to 400 meters from cellphone towers, which emit more EMR, has been found to be associated with an increased cancer incidence. In any case, access to such rooftop areas with cellular antennas should be restricted or limited [69]. Actually, defraying the total EMR load in this way may be one potential method of decreasing total human exposure in urban neighborhoods. Dividing up the EMR load between several buildings in an urban area could help to minimize overall individual microwave exposure, while having one large cellphone tower in

According to various animal studies, there appears to be a significant effect of microwaves in the cellphone tower frequency range on mammals, avian species, and insect pollinators such as honey bees. There also appears to be a negative impact on plant life in the vicinity of cellphone towers. Decreases in fruit and other crop yields could translate into economic losses. As a result, some countries like India have already taken positive action against the potential threat of cellphone tower EMR to wildlife by proposing to have EMR levels audited and recognized as a pollutant and passing a special law to safeguard the surrounding environment. Other countries should also follow suit in setting safe environmental limits on EMR emission levels from cellphone towers in order to preserve the urban flora and fauna. Such safety standards should always be based on the latest research and must be subject to constant revision as new

the same area would tend to maximize the microwave exposure of a few.

Address all correspondence to: moondustcosmetics@gmail.com

4 President and Primary Biochemist of Moondust Cosmetics Ltd., Canada

3 Medical College Wisconsin, Milwaukee, WI, USA

absorption rate (SAR).

data become available.

Chanda Siddoo-Atwal1,2,3,4

1 University College London, UK 2 Simon Fraser University, Canada

Author details

In summary, various laboratory studies on animals and certain human data [68] are suggestive that tumor formation requires at least two discrete events to take place in response to a carcinogen. The first involves an elevation of apoptosis in a particular tissue due to a genetic predisposition, stress, or mutation. The second confers resistance to apoptosis in that same tissue resulting in the formation of an abnormal growth due to a dysregulation of cell number homeostasis. Moreover, there is some evidence to suggest that both these events can be reversible when treated with a selective apoptotic agent and, hence, they may be either genetic or epigenetic in nature.

Thus, according to this new model, apoptosis becomes an important focus of study and key determinant of carcinogenic potential for any particular chemical or other complete carcinogen being studied, especially in normal, non-transformed cells derived from the target tissue [11].

In the microwave radiation exposure model, there are a number of cellular processes and responses that appear to lead to the endpoint of an increased rate of apoptosis in both animals and humans. These parameters include DNA damage, alterations in gene expression, metabolic perturbations in intracellular calcium levels, effects on the immune system involving decreases in natural killer cells and T lymphocytes, and bursts in ROS activity. All these biochemical effects represent early events that can trigger or are linked to apoptosis and, therefore, could be involved in initiating an apoptotic model of carcinogenesis as described above.
