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Lymphoma Development of Simultaneously Combined Exposure to Two Radiofrequency Signals in AKR/J Mice
Abstract
There are public concerns regarding possible carcinogenic or cancer-promoting effects of radiofrequency electromagnetic fields (RF-EMFs) because of the extensive use of wireless mobile phones and other telecommunication devices in daily life. However, so far it is unclear if non-thermal exposure of single EMF exposure in animal studies has a direct influence on carcinogenesis. Here, carcinogenic effects of combined signal RF-EMFs on AKR/J mice, which were used for the lymphoma animal model, were investigated. Six-week-old AKR/J mice were simultaneously exposed to two types of RF signals: single code division multiple access (CDMA) and wideband code division multiple access (WCDMA). AKR/J mice were exposed to combined RF-EMFs for 45 min/day, 5 days/week, for a total of 42 weeks. The whole-body average specific absorption rate (SAR) of CDMA and WCDMA fields was 2.0 W/kg each, 4.0 W/kg in total. When we examined final survival, lymphoma incidence, and splenomegaly incidence, no differences were found between sham- and RF-exposed mice. However, occurrence of metastasis infiltration to the brain in lymphoma-bearing mice was significantly different in RF-exposed mice when compared to sham-exposed mice, even though no consistent correlation (increase or decrease) was observed between male and female mice. However, infiltration occurrence to liver, lung, and spleen was not different between the groups. From the results, we suggested that simultaneous exposure to CDMA and WCDMA RF-EMFs did not affect lymphoma development in AKR/J mice.
... Regarding carcinogenesis, the selected 27 papers reported the results of 66 different treatment groups: most of the papers (14) analyzed only one treatment group, [61][62][63][64][65][66][67][68][69][70][71][72][73][74], five articles reported two treatment groups [75][76][77][78][79], two articles had three treatment groups [80,81], one article had four treatment groups [82], four articles had six treatment groups [31,32,83,84] and, finally, one article had eight treatment groups [85]. A summary of the most relevant information of the 66 treated-sham control comparisons in terms of populations, exposure and outcomes is reported in Appendix A. Regarding the type of animals (POPULATION) employed in the selected papers, a total of 12 papers (30 treatment groups) described experiments performed on rats, and the remaining 15 papers (36 treatment groups) used mice ( Figure 2a). ...
... In this case, the overall RR value is 1.08 (1.03-1.14). [31,32,[61][62][63][64][65][66][67][68][69]71,72,74,75,76,79,81,82,85]. ...
The increasing exposure of the human population to radiofrequency electromagnetic fields has increased concern about its possible health effects. The aim of this systematic review is to provide an update of the state of the research on this topic, through a quantitative analysis, to assess the increased risk of tumor incidence in laboratory animals (rodents) without limitations of species, strain, sex or genotype. The review was conducted according to the PRISMA guideline and individual studies were assessed by referring to the OHAT Risk of Bias Rating Tool for Human and Animal Studies. A total of 27 studies were considered eligible for the evaluation of tumor incidence; a meta-analysis was carried out on 23 studies to assess the possible increased risk of both malignant and benign tumors onset at the systemic level or in different organs/tissues. A significant association between exposure to RF and the increased/decreased risk of cancer does not result from the meta-analysis in most of considered tissues. A significant increased/decreased risk can be numerically observed only in heart, CNS/brain, and intestine for malignant tumors. Nevertheless, the assessment of the body of evidence attributes low or inadequate evidence for an association between RF exposure and the onset of neoplasm in all tissues.
... Vingt-cinq études réalisées à des fréquences différentes sur le même paramètre chez l'animal ont été identifiées (Shirai et al., 2005, Ferreira et al., 2006, Shirai et al., 2007, Smith et al., 2007, Lee et al., 2009, Mailankot et al., 2009, Sirav and Seyhan, 2009, Ziemann et al., 2009, Franzellitti et al., 2010, Markova et al., 2010, Lee et al., 2011, Paulraj and Behari, 2011, Sirav and Seyhan, 2011, Lee et al., 2012, Ozorak et al., 2013, Cetin et al., 2014, Nisbet et al., 2016, Ertilav et al., 2018, Alkis et al., 2019, Wang et al., 2019, Yinhui et al., 2019, Furman et al., 2020, Lameth et al., 2020 Parmi elles, 4 ont été écartées car elles analysaient en réalité une seule fréquence (Ferreira et al., 2006, Franzellitti et al., 2010, Furman et al., 2020, Lameth et al., 2020. Trois autres ont été écartées car elles utilisaient plusieurs fréquences, mais simultanément (Lee et al., 2009, Lee et al., 2011, Lee et al., 2012. ...
... Vingt-cinq études réalisées à des fréquences différentes sur le même paramètre chez l'animal ont été identifiées (Shirai et al., 2005, Ferreira et al., 2006, Shirai et al., 2007, Smith et al., 2007, Lee et al., 2009, Mailankot et al., 2009, Sirav and Seyhan, 2009, Ziemann et al., 2009, Franzellitti et al., 2010, Markova et al., 2010, Lee et al., 2011, Paulraj and Behari, 2011, Sirav and Seyhan, 2011, Lee et al., 2012, Ozorak et al., 2013, Cetin et al., 2014, Nisbet et al., 2016, Ertilav et al., 2018, Alkis et al., 2019, Wang et al., 2019, Yinhui et al., 2019, Furman et al., 2020, Lameth et al., 2020 Parmi elles, 4 ont été écartées car elles analysaient en réalité une seule fréquence (Ferreira et al., 2006, Franzellitti et al., 2010, Furman et al., 2020, Lameth et al., 2020. Trois autres ont été écartées car elles utilisaient plusieurs fréquences, mais simultanément (Lee et al., 2009, Lee et al., 2011, Lee et al., 2012. Quatre autres n'ont pas été retenues car les auteurs n'avaient constaté aucun effet à aucune des fréquences étudiées (Shirai et al., 2005, Shirai et al., 2007, Smith et al., 2007, Ziemann et al., 2009. ...
After an indication of the numerous interveners who participated to this expertise study, and a presentation of the context, objective and methodology of this expertise, this report, based on a very large bibliography, discusses the various aspects of the '5G' deployment and the associated public controversy: situation of the deployment in France and abroad, problems raised, actors involved in the controversy, media content, health framework, and posture of the academic community. It describes international institutional positions with respect to health effects of the '5G' (by international bodies, foreign national institutions, and in the USA, Australia and New-Zealand, and Europe). In the next part, exposure data related to the '5G' are reported and compared: normative and regulatory framework, technological evolutions regrading the 5G bandwidth, assessment of the exposure level in the lower bandwidths. By referring to various public or scientific publications from different countries, it proposes a rather detailed overview of health effects related to the studied exposure (comments about scientific knowledge and acknowledgement, the different biological effects on the human body). Some recommendations, notably regarding the deployment of '5G', are finally presented. A second document presents the opinion of the ANSES (the French Agency for health safety) about the content of this report.
... The few studies there have been in this area have not clearly identified potential health risks related to multiple RF exposure: no relationship has been established between multifrequency exposure and cellular alterations in embryos during gestation [2], alteration of testicular function [3], toxic or carcinogenic effects [4,5], or chronic symptoms such as headaches or sleep alterations in adults [6] and children [7]. Nevertheless, the paucity of information on the possible bio-effects of multiple RF signals contrasts with the concern of the general public and of various governmental entities [8,9]. ...
... There have been several reports that non-thermal levels of RF radiation can increase apoptosis in response to ionizing ultra-violet or gamma radiation [42,43]. Studies investigating whether such synergism extends to exposure to multiple radio frequencies have been few, and their results, like ours, negative, whether epidemiological [2,3] or experimental [4][5][6][7]. In the present case, the absence of significant effects may have been due in part to the low specific absorption rates employed (< 0.3 W/kg except in the pituitary glands of group 3) and the use of just a single exposure period rather than repeated exposures. ...
Simultaneous exposure to multiple electromagnetic signals with widely differing carrier frequencies is a reality of daily life, but its possible effects on health are unknown. In this study, we exposed rats to non-thermal levels of 900 and 2450 MHz TEM-mode radiation, applied individually or simultaneously, and we obtained estimates of 1 g mean SAR (specific absorption rate) in various tissues using a numerical model of the rat and finite-difference time-domain software. The experimental system comprised a GTEM (gigahertz TEM) chamber connected to two vector signal generators, a signal mixer and amplifier, a directional coupler, a spectrum analyzer and a power meter. Tissue sections from rats sacrificed 24 h after exposure, and from negative controls and positive controls exposed to gamma radiation, were stained with haematoxylin-eosin for evaluation of general cell morphology and with DAPI (4', 6-diamidino-2-phenylindole) for evaluation of apoptosis. Lesions, tissue destruction and apoptosis were only observed in positive controls. The results for rats exposed to either frequency, or to both simultaneously, were similar to those of unexposed negative controls. It remains to determine whether chronic exposure is similarly innocuous.
... It is still controversial as to whether cell-phone RF-EMF increases the risk of brain cancer (Shirai et al. 2007, Aydin et al. 2011, Lee et al. 2011. However, recently, the World Health Organization (WHO) changed its position from there being no link between cell-phone RF-EMF and brain cancer to listing the RF-EMF of cell phones in the ' carcinogenic hazard ' category (Moussa 2011). ...
... Th e calculated SAR values were then averaged and multiplied by the measured root-mean-square (RMS) electric fi eld value to estimate real SAR values for a given input power (Lee et al. 2011). Th e electromagnetic waves in the experimental region of the reverberation chamber came from all directions, with equal amplitude. ...
Purpose:
We investigated the effect of whole-body exposure to 915-MHz radiofrequency identification (RFID) on rat cortical glucose metabolism by using (18)F-deoxyglucose positron emission tomography (FDG-PET).
Materials and methods:
Male Sprague-Dawley rats were divided into three groups: Cage-control, sham-exposed and RFID-exposed groups. Rats were exposed to the 915-MHz RFID for 8 h daily, 5 days per week, for 2 or 16 weeks. The whole-body average specific absorption rate (SAR) was 4 W/kg for the field of the 915 MHz RFID signal. FDG-PET images were obtained the day after RFID exposure, using micro-PET with a FDG tracer. With a Xeleris functional imaging workstation, absolute values in regions of interest (ROI) in the frontal, temporal and parietal cortexes and cerebellum were measured. Cortical ROI values were normalized to the cerebellar value and compared.
Results:
The data showed that the relative cerebral glucose metabolic rate was unchanged in the frontal, temporal and parietal cortexes of the 915 MHz RFID-exposed rats, compared with rats in cage-control and sham-exposed groups.
Conclusion:
Our results suggest that 915 MHz RFID radiation exposure did not cause a significant long lasting effect on glucose metabolism in the rat brain.
... The mice were exposed to RF-EMF for 45 min/day, 5 days/ week, over a total of 42 weeks. The thymus showed significant enlargement in most mice, and the thymoma was abnormal tissue (Lee et al. 2011). Misa-Agustino et al. exposed different levels of microwave radiation on rats. ...
This study aims to investigate the effects of pre- and postnatal 2450 MHz continuous wave (CW) radiofrequency radiation (RFR) on the thymus of rats spanning four generations. Four groups; sham, irradiated female, irradiated male, irradiated male and female, each consisting of four rats (one male and three females), were created. During the experiment, rats in the exposure groups were whole-body exposed to 2450 MHz CW-RFR for 12 h/day. Irradiation started one month before the fertilization in the experimental group. When the offspring were two months old, four rats, one male and three female, were allocated for the second-generation study. The remaining offspring were sacrificed under general anesthesia, and their thymuses were removed. The same procedure was applied to the next generation. Two months after the second generation gave birth, third-generation rats were decapitated, and their thymuses were removed. In all groups, cortex, medulla and resident cells could be clearly distinguished in the second and third generations. No differences were observed between the control and two experimental groups, defined as irradiated female and irradiated male. In contrast, vascularization was observed in the thymus of the fourth-generation offspring of the group where both males and females were irradiated. The number of offspring and mass of all rats decreased in the third-generation group. Pre-and postnatal 2450 MHz continuous wave radiofrequency radiation exposure may potentially affect the thymus of future generations.
... The accumulative exposure of the 2.856 GHz and 1.5 GHz microwaves aggravated the downregulation of p-CREB/CREB. Previous studies used combined exposure to communication microwaves (849 MHz and 1.95 GHz), but none of these studies analyzed the interaction effects [53][54][55][56] . ...
This study aimed to evaluate the acute effects of 2.856 GHz and 1.5 GHz microwaves on spatial memory and cAMP response element binding (CREB)-related pathways. A total of 120 male Wistar rats were divided into four groups: a control group (C); 2.856 GHz microwave exposure group (S group); 1.5 GHz microwave exposure group (L group); and 2.856 and 1.5 GHz cumulative exposure group (SL group). Decreases in spatial memory abilities, changes in EEG, structural injuries, and the downregulation of phosphorylated-Ak strain transforming (p-AKT), phosphorylated-calcium/calmodulin-dependent protein kinase II (p-CaMKII), phosphorylated extracellular signal regulated kinase (p-ERK) and p-CREB was observed 6 h after microwave exposure. Significant differences in the expression of p-CaMKII were found between the S and L groups. The power amplitudes of the EEG waves (θ, δ), levels of structural injuries and the expression of p-AKT, p-CaMK II, p-CREB, and p-ERK1/2 were significantly different in the S and L groups compared to the SL group. Interaction effects between the 2.856 and 1.5 GHz microwaves were found in the EEG and p-CREB changes. Our findings indicated that 2.856 GHz and 1.5 GHz microwave exposure induced a decline in spatial memory, which might be related to p-AKT, p-CaMK II, p-CREB and p-ERK1/2.
... Research focused on assessing the risk levels associated with RF exposure for carcinogenic effects. The animal in vivo studies identified by ANSES in [24] did not evidence that exposure to nonthermal exposure levels causes the initiation or the promotion of cancer [47], [48]. related to the regular mobile use [52]- [56]. ...
The evolution and increasing use of mobile communications systems was associated with laboratory investigations to study radiofrequency electromagnetic waves exposure safety. In this context, this thesis focuses on the characterization of exposure systems allowinglaboratory in vitro studies on cell models. A dual numerical and experimental approach is implemented to perform the devices dosimetry allowing to determine and control the exposure levels. One of the limitations associated with this dosimetry is due to the micrometric dimensions involved. Therefore, a microscopy technique based on a temperature-dependent fluorescent dye named Rhodamine B was set up and evaluated. This assessment recommends an optimal concentration of the dye at around 50 μM. After calibration, it is possible to estimate the specific absorption rate (SAR) from the temperature variation, even for low levels of SAR (< W / kg) with a spatial resolution of less than ten micrometers i.e. microdosimetry. The two main exposure systems studied, based on microelectrode arrays (MEA), allow the recording of neurons electrophysiological activity. Exposure to electromagnetic waves is achieved simultaneously by inserting these MEAs into TEM cells exposure systems. Dosimetry carried out at 1.8 GHz shows a higher sensitivity of one MEA to its environment. It was shown that the modifications made to the second MEA such as its aperture size and ground planes, have reduced the proximity environment influence. The microdosimetry demonstrated good homogeneity of the SAR between the electrodes with an estimated value of 7 ± 1 W / kgfor 1 W incident power. Finally, a microfluidic exposure device based on a coplanar waveguide was characterized under static conditions.
... Those studies using tumor-susceptible and genetically altered animals were not focused on evaluating RFR carcinogenic potential, but rather on investigating the effects in the specific target sites in that particular model [29,30]. Furthermore, some of the studies made with tumor-prone laboratory animals did not expose the animals to RFR for sufficient time (< 1 year), and for this reason, were not included in this review [82][83][84]. Lastly, additional points of criticism are the limited number of organs assessed for histopathology and inadequate group sizes (<50 animals/sex/group). ...
The proliferation of cellular antennas and other radiofrequency radiation (RFR) generating devices of the last decades has led to more and more concerns about the potential health effects from RFR exposure. Since the 2011 classification as a probable carcinogen by the International Agency for Research on Cancer (IARC), more experimental studies have been published that support a causal association between RFR exposure and health hazards. As regard cancer risk, two long-term experimental studies have been recently published by the US National Toxicology Program (NTP) and the Italian Ramazzini Institute (RI). Despite important experimental differences, both studies found statistically significant increases in the development of the same type of very rare glial malignant tumors. In addition to carcinogenicity, reproductive organs might be particularly exposed, as well as sensitive to RFR. In this work, we reviewed the currently available evidence from in vivo studies on carcinogenicity and reproductive toxicity studies in order to summarize the contribution of experimental research to the prevention of the adverse effects of RFR on human health.
... Legal limits on the specific absorption rate (SAR) associated with exposure to multiple signals (REAL DECRETO 1066 have not been established based on experimental evidence, and there is accordingly significant uncertainty regarding the effectiveness of these limits. Only a handful of epidemiological (Thomas et al. 2008a(Thomas et al. , 2008b, in vitro (Kang et al. 2014), or in vivo (Lee et al. 2011L opez-Furelos et al. 2012L opez-Furelos et al. , 2016 studies have been done for exposure to combined RF. ...
Purpose: The aim of this study was to determine whether exposure to radiation from single or multiple radio-frequency (RF) signals at 900 and 2450 MHz would induce effects in the RAW 264.7 cell line.
Materials and Methods: Cell cultures were exposed to single or combined RF for 4, 24, 48 or 72 hours in a GTEM electromagnetic test chamber. At the end of the radiation exposure time, viability and cell growth were analyzed by flow cytometry, nitric oxide (NO) production was measured by colorimetry, the expression of HSP70 and TNF-α was ascertained by qPCR and phagocytic activity was observed by microscopy.
Results: NO production increased after 48 hours exposure at 2450 MHz, compared to controls. The group subjected to the combined interaction of two RFs showed an increase of HSP70 after 48 hours exposure and a significant increase of NO and TNF-α after 72 hours. The phagocytic activity of macrophages decreased in all groups as exposure time increased.
Conclusions: Our results indicated a decrease in phagocytic activity and an increase in inflammatory, cytoprotective and cytotoxic responses in macrophages after continuous and combined exposure of multiple RF signals. Multiple RF interact in everyday life, the immune response in humans is unknown.
... Additional studies of the effect of RFR on tumorigenesis in tumor-prone models, including Ptc1 +/À knockout mice (brain tumors), Em-Pim1 transgenic mice (lymphomas), AKR mice (lymphomas and other hematopoietic neoplasms), and C3H mice (mammary tumors) have yielded conflicting results [Repacholi et al., 1997;Toler et al., 1997;Frei et al., 1998a,b;Utteridge et al., 2002;Sommer et al., 2004Sommer et al., , 2007Oberto et al., 2007;Saran et al., 2007;Lee et al., 2011]. Furthermore, the value of several of these studies in assessing carcinogenicity of RFR is also reduced by limitations in study design and/or RFR exposures. ...
Radiofrequency radiation (RFR) causes heating, which can lead to detrimental biological effects. To characterize the effects of RFR exposure on body temperature in relation to animal size and pregnancy, a series of short-term toxicity studies was conducted in a unique RFR exposure system. Young and old B6C3F1 mice and young, old, and pregnant Harlan Sprague-Dawley rats were exposed to Global System for Mobile Communication (GSM) or Code Division Multiple Access (CDMA) RFR (rats = 900 MHz, mice = 1,900 MHz) at specific absorption rates (SARs) up to 12 W/kg for approximately 9 h a day for 5 days. In general, fewer and less severe increases in body temperature were observed in young than in older rats. SAR-dependent increases in subcutaneous body temperatures were observed at exposures ≥6 W/kg in both modulations. Exposures of ≥10 W/kg GSM or CDMA RFR induced excessive increases in body temperature, leading to mortality. There was also a significant increase in the number of resorptions in pregnant rats at 12 W/kg GSM RFR. In mice, only sporadic increases in body temperature were observed regardless of sex or age when exposed to GSM or CDMA RFR up to 12 W/kg. These results identified SARs at which measurable RFR-mediated thermal effects occur, and were used in the selection of exposures for subsequent toxicology and carcinogenicity studies. Bioelectromagnetics. 9999:1-10, 2018. © 2018 The Authors. Bioelectromagnetics Published by Wiley Periodicals, Inc.
... As far as animal studies were concerned, exposure of AKR/J mice (used as lymphoma model) to RF-EMF for 45 min/day, 5 days/week, for a total of 42 weeks (SAR 4.0 W/kg) did not generate differences in lymphoma and splenomegaly incidence between sham-and exposed animals (Lee et al., 2011). This finding confirmed a previous evidence showing, in AKR/J mice, the lack of effects from exposure to UMTS test signals (24 h per day, 7 days per week, 0.4 W/kg SAR) (Sommer et al., 2007). ...
The spread of radiofrequency electromagnetic fields (RF-EMF) is rising and health effects are still under investigation. RF-EMF promote oxidative stress, a condition involved in cancer onset, in several acute and chronic diseases and in vascular homeostasis. Although some evidences are still controversial, the WHO IARC classified RF-EMF as "possible carcinogenic to humans", and more recent studies suggested reproductive, metabolic and neurologic effects of RF-EMF, which are also able to alter bacterial antibiotic resistance. In this evolving scenario, although the biological effects of 5G communication systems are very scarcely investigated, an international action plan for the development of 5G networks has started, with a forthcoming increment in devices and density of small cells, and with the future use of millimeter waves (MMW). Preliminary observations showed that MMW increase skin temperature, alter gene expression, promote cellular proliferation and synthesis of proteins linked with oxidative stress, inflammatory and metabolic processes, could generate ocular damages, affect neuro-muscular dynamics. Further studies are needed to better and independently explore the health effects of RF-EMF in general and of MMW in particular. However, available findings seem sufficient to demonstrate the existence of biomedical effects, to invoke the precautionary principle, to define exposed subjects as potentially vulnerable and to revise existing limits. An adequate knowledge of pathophysiological mechanisms linking RF-EMF exposure to health risk should also be useful in the current clinical practice, in particular in consideration of evidences pointing to extrinsic factors as heavy contributors to cancer risk and to the progressive epidemiological growth of noncommunicable diseases.
... In the other study, young AKR/J mice (which express the ecotropic retrovirus AKV in all tissues and spontaneously develop lymphoma) were exposed to combined CDMA and WCDMA signals for 45 min/day, 5 day/week for 42 weeks (49). Compared to sham-exposed controls, exposure had no significant effect on weight, survival time, or incidence of lymphoma. ...
There is an extensive literature investigating possible effects of exposure to radiofrequency (RF) electromagnetic fields associated with mobile phone technologies. This has not identified any public health risks with any degree of certainty. Some epidemiological studies have observed associations between heavy users of mobile phones and some types of cancer, but animal studies do not support this association, although a few studies have reported increased tumor yields. However, there is a crucial difference between epidemiology studies and laboratory work in terms of signals investigated: most people are exposed to a complex mixture of frequencies and signals at varying intensities, whereas the majority of animal studies have been performed using a single frequency or intensity. Whether this might explain the differences in outcome will be discussed, and whether there is a need for additional laboratory investigations that reproduce more accurately realistic exposure conditions will be considered.
... 113 Lee et al. (2011) exposed 6 week-old AKR/J mice to RF-EMF at a total SAR of 4 W/kg for 45 minutes per day, 5 days per week over 42 weeks. 114 There was no increase in lymphoma detected between the exposed mice and sham controls. ...
Epidemiological studies including the large-scale Hardell, Interphone, and CERENAT studies indicate
that long-term cell phone use is associated with an elevated risk of brain cancer. A key concern is the
rapid escalation in the number of children <12 years of age who are becoming cell phone users. Resultant
long-term use patterns might increase brain tumor risk and become a substantial societal burden. However,
published human studies addressing cell phone use and brain cancer risk involve data-quality limitations.
The Hardell, Interphone, and CERENAT studies have been regarded by some analysts with skepticism, and
a significant number of reports have not demonstrated a link between cell phones and brain cancer. On the
other hand, other interpretations, as well as other studies, have argued for a strong link. This places
added importance on cell-based and animal-model research to demonstrate a plausible mechanism by
which RF-EMF can cause genotoxic effects and increase the frequency of brain tumors. The current
body of published cell-based and animal studies exhibits wide variation in study parameters, conditions,
and scientific rigor and contains conflicting results. Given the weaknesses of human population
and laboratory studies, it may be premature at the present stage to abandon further explorations and
deliberations of brain tumor risk from exposure to cell phone RF-EMF. In fact, given the potential societal
impact, we advocate for increased support of systematic scientific studies to address this link.
... Humans are also simultaneously exposed to multi-signal RF and there is very little information about the biological effects of this. Only a very few epidemiological [1,2], in vitro [3] or in vivo [4,5] studies have been done for exposure to combined RF. It remains unclear whether there are repercussions on human health. ...
Multiple simultaneous exposures to electromagnetic signals induced adjustments in mammal nervous systems. In this study, we investigated the non-thermal SAR (Specific Absorption Rate) in the cerebral or cerebellar hemispheres of rats exposed in vivo to combined electromagnetic field (EMF) signals at 900 and 2450 MHz.
Forty rats divided into four groups of 10 were individually exposed or not exposed to radiation in a GTEM chamber for one or two hours. After radiation, we used the Chemiluminescent Enzyme-Linked Immunosorbent Assay (ChELISA) technique to measure cellular stress levels, indicated by the presence of heat shock proteins (HSP) 90 and 70, as well as caspase-3-dependent pre-apoptotic activity in left and right cerebral and cerebellar hemispheres of Sprague Dawley rats.
Twenty-four hours after exposure to combined or single radiation, significant differences were evident in HSP 90 and 70 but not in caspase 3 levels between the hemispheres of the cerebral cortex at high SAR levels. In the cerebellar hemispheres, groups exposed to a single radiofrequency (RF) and high SAR showed significant differences in HSP 90, 70 and caspase-3 levels compared to control animals. The absorbed energy and/or biological effects of combined signals were not additive, suggesting that multiple signals act on nervous tissue by a different mechanism.
... Moreover, this information is fundamental for exposure assessment in epidemiological studies and in the design of biological exposure systems for both in vitro and in vivo investigations [10]. However, only a few studies have been performed so far considering exposures to multiple sources [11]–[15] or seeking to define real life scenarios of combined exposures to different RF signals [16]–[19]. ...
A standardized exposure device, already used at 1.95 GHz for in vitro bioelectromagnetic studies, has been further characterized and upgraded for exposing cell cultures to single or multiple frequencies used by information and communication technologies, such as GSM, Universal Mobile Telecommunication System, and Wi-Fi systems. The applicator consists of a customized WR-430 waveguide, and cell culture exposures can be performed in either a one- or multiple-sample configuration. Single-frequency scenarios were characterized for exposures at 1.8, 1.95, and 2.45 GHz, obtaining high efficiency (ranging from 51% to 87% in the single-sample exposure and from 60% to 93% in the multiple-sample exposure) and acceptable nonuniformity degree (about 33% in all cases). Moreover, optimization and characterization for exposures to multiple signals, either simultaneously or in close sequence, were also carried out with good results (efficiency ranging from 30% to 40% and nonuniformity degree of about 35%). Numerical dosimetry was validated by measurements (scattering parameters and calorimetric measurements through infrared camera) and a very satisfying agreement has been found between simulations and experimental data.
This study was initiated to establish whether spatio-spectral Eigen-modes of EEG brain waves can be described by an Acoustic Quantum Code of Resonant Coherence, as found by us earlier in a spectrum of animate and inanimate systems. Presently available EEG-and MEG recordings were analyzed as to their peak frequencies in relation to our Quantum Code coherence values. Both the EEG-and MEG studies of healthy persons exhibited quantum coherence of EEG peaks with mean quantum coherence of 0.95 (an average of 90-100% showed coherent peak values), while in patient groups with various mental disorders, a significant decrease of coherence correlation was found. ADHD subjects show a moderate change in peak coherence, being in the range of 1.0 to 0.83, while during epileptic seizures the degree of peak coherence is reduced to a range of 0.94 to 0.75. Depressed patients have EEG peaks with a consistently lower coherence values than healthy persons: 0.77-0.88, while autistic persons show an even lower coherence of 0.50 till 0.75. Patients with severe psychiatric disorders, such as depression, show a coherence of only 0.49-0.61. The importance of EEG brain coherence for conscious states was demonstrated in patients under anaesthesia that exhibited a very low coherence level of about 0.25. The graded loss of brain EEG coherence combined with alterations in Phi based EEG wave separation, can therefore be of value for differentiation in severity and nature of neurological disorders. The value of our frequency algorithm was also shown for trans-cranial therapy: the presently chosen frequencies of rTMS therapy in clinical practice correspond very well with the values of our algorithm. Of interest, the Acoustic Quantum Code pattern was also shown to describe neuronal microtubular (MT) wave frequencies, as measured in vitro by others. MT oscillations were claimed by Hameroff and Penrose to be instrumental in the creation of brain consciousness through alignment with gravity fluctuation at the Planck scale. Our results on brain EEG coherence are therefore discussed in relation to the current models for understanding the nature of (self)-consciousness. We regard the potential relation between neuronal coherence/decoherence balance and conscious states as a central mechanism for producing quantum entanglement in the brain as related to long-distance neuro-communication and brain binding. As postulated earlier, consciousness can be modelled by a 5D brain-associated, toroidal workspace, that provides quality control and monitoring of integral brain function, according to holographic principles and was earlier framed as the "Event Horizon Brain". Consciousness, in this concept, requires photon/phonon mediated and resonant communication with this field-receptive holographic workspace, seen as associated with but not reducible to the human brain. The related brain supervening role of the event horizon workspace requires the collective conscious and unconscious states and realizes a total holographic modality of consciousness that enables effective predictive coding. This 5D, scale invariant, memory workspace, therefore, can be instrumental in the manifestation of Psi phenomena and experiences of cosmic consciousness. At the sub-atomic level, gravity guided quantum tunnelling and coherence of micro-tubular oscillations may produce neuronal entanglement. The latter represents a dominant factor in long distance neural information transfer and functional brain binding. The resulting synchronization of neural network frequencies is likely reflected in the abovementioned brain coherency of EEG peaks, as well as in various mental states that promote feelings of mental wholeness in meditation and psycho-mimetic drug therapy. 2
A new biomarker is proposed, that shows a diagnostic capability to classify a measure of healthy and unhealthy behaviour by analysing the pattern of brain waves related to discrete frequencies and amplitudes. Discrete frequencies fit in a coherent or in a decoherent frequency pattern and has been substantiated by a quantum physical model about phase-synchronisation of the spectral lines of EEG (Electroencephalography) and MEG (Magnetoencephalography). Phase-synchronisation and spatio-spectral eigenmodes have been shown for our brains and is related to a discrete distribution of energy: En= ħ ωref 2 n+p 3 m. The model shows that the overall resonating spatio-spectral states of living cells and molecules including brain cells can be described by a sum of quantum coherent and decoherent frequencies. Healthy states are quantum coherent and approach a global quantum coherence of 1.0, while unhealthy states are decoherent and cause a decrease of coherence. The proposed model of spatio-spectral eigenmodes has been substantiated by analysing the many measured frequency patterns of EEG's and MEG's, and electromagnetic exposures of brain cells, glands and neurons. The EEG-and MEG studies of healthy persons show a global quantum coherence of 0.90-1.00. Unhealthy subjects show a decrease of coherence, and an increase of decoherence. ADHD subjects show a decrease of coherence from 1.0 to 0.83. During epileptic seizure, the coherence of participants is reduced from 0.94 to 0.75. Depressed patients have a lower coherence than healthy persons: 0.77-0.88, autistic persons show a lower coherence of 0.50 till 0.75, patients with severe psychiatric disorders show a coherence of about 0.59, and participants during anaesthesia show a level of 0.25. Repetitive transcranial magnetic stimulation (rTMS) has been reported to modify brain oscillations and the periodic electromagnetic force generated during rTMS can result in local entrainment of biologically relevant rhythms, mimicking frequency specific oscillatory activities. Potential differential effects occur at typical frequencies: 0.50, 0.75, 1, 5, 6, 8, 9, 10, 12, 15, 17, 20, 25, 40 Hz, that are equal or approach the proposed algorithm, and fit with the eigenstates (eigenfrequencies) described by the proposed equation of coherence. The coherent and decoherent (chaos-like) frequencies can be aligned at a frequency scale and are arranged according to an alternating ordering positioned at a toroidal geometry, while transition frequencies are located just in between the coherent and decoherent frequency zones. The overall results show a presence of an informational quantum code and a molecular code-script, which supplies information to realize biological order in life cells and substantiates a collective Bose-Einstein type of behaviour. Typical nano/submicron minerals can copy healthy behaviour of living cells.
Conformational states of living cells have typical spatial arrangements of atoms, that are characteristic for building, homeostasis, decay and apoptosis. We earlier found clear evidence, indicating that such states of biomolecules are related to spectral coherence and decoherence frequency bands, providing a quantitative physical resource. The patterned arrangements of EMF frequencies can be described by electromagnetic wave patterns positioned on an acoustic scale, on the basis of an underlying quantum wave equation. The proposed equation shows a discrete distribution of energy: En= ħ ωref 2 n+p 3 m , that supports quantum entanglement, and is in line with the earlier published models of Fröhlich and Davydov. The overall results show the presence of a molecular code-script, which supplies information to realize biological order in life cells and substantiates collective (Bose-Einstein) type of coherent wave behaviour. The particular wave equation was inferred from a meta-analysis of 724 biomedical publications, from 1970 till 2020, reporting either beneficial or detrimental biological effects caused by external non-thermal EMF-frequencies from ELF till THz. Based on this new biophysical principle, evidence is provided to support a causal relation between exposure of electromagnetic waves and healthy (or a non-influence) and unhealthy effects for living cells and biomolecules. External exposures to non-thermal at KHz, MHz-and GHz electromagnetic waves can therefore lead to unhealthy conditions depending on wave frequency, pulsing properties, field intensity, average absorption rate of the cells (W/kg) and exposure time. An additional analysis of 241 experiments confirms that non-thermal electromagnetic waves can induce significant changes in human cells. The currently applied single or composed frequencies in communication technology, fit for 94.2% with the proposed quantum model related to either healthy or unhealthy behaviour. For example, up to 80% of the planned 5G frequencies possibly belong to the detrimental decoherent or modulated coherent frequency bands. Further research to counteract non-thermal unhealthy electromagnetic effects can generate ideas for improving the balance between coherent and decoherent waves, and thereby may open a potential novel road to innovative health technologies. 2
Many studies have revealed the cognitive decline induced by microwave radiation. However, the systematic study on dose-dependent, frequency-dependent and accumulative effects of microwave exposure at different frequencies was lacking. Here, we studied the relationship between the effects and the power and frequency of microwave and analyzed the accumulative effects of two different frequency microwaves with the same average power density. After microwave radiation, declines in spatial learning and memory and fluctuations of brain electric activities were found in the 10 mW/cm² single frequency exposure groups and accumulative exposure groups. Meanwhile, morphological evidences in hippocampus also supported the cognitive dysfunction. Moreover, the decrease of Nissl contents in neurons indicated protein-based metabolic disorders in neurons. By detecting the key functional proteins of cholinergic transmitter metabolism, cytokines, energy metabolism and oxidative stress in the hippocampus, we found that microwave could lead to multiple metabolic disorders. Our results showed that microwave-induced cognitive decline was largely determined by its power rather than frequency. Injury effects were also found in accumulative exposure groups. We particularly concerned about the safety dose, injury effects and accumulative effects of microwaves, which might be very valuable in the future.
The aim of this work was to simulate human exposure to high power pulsed microwave (HPM) emitted by radars of the French Navy. Navy staff exposure to radars may be occasional, prolonged or repeated depending on activities aboard. It was necessary to investigate their potential health effects in order to contribute to the risk assessment and anticipate potential litigation. A special emitting experimental device was developed in order to reproduce different exposure conditions at 3 GHz with an experimental model of adult rat. We present here the in vivo results obtained after 3 GHz exposure under non thermal conditions - acute (DAS 5 W/kg), chronic (DAS 15 W/kg) and chronic associated with repeated acute exposure (mixed) –for short, middle and long term effects on adult rat. The dosimetry was obtained by numerical simulation (FDTD) and completed with experimental measurements. Parameters related to the central nervous system, especially on blood brain barrier (BBB) and apoptosis were observed. The effects on cognitive function were assessed by different types of behavioral tests on memory, learning, anxiety, aggressiveness and locomotion of adult rat. Regular body weighing and clinical check-up including tumor incidence with sampling and histological examination were performed on rats. In parallel, hematological parameters were examined with complete blood count and immunological system was studied. The endocrine pathway involved in stress management have been studied through adrenocorticotrope hormone (ACTH) and corticosterone assays. No significant behavioral effect either on memory, learning, anxiety, aggressiveness, overall neurological evaluation either or on locomotion of adult rat. Results did not show any effect on central nervous system in our experimental conditions. No significant effect was observed on weight gain of rats after non thermal microwave exposure. Results on hematological parameters, on immunological parameters, on stress hormones and on tumors development did not detected any non thermal effect in our experimental conditions
Several reports indicated that non-thermal electromagnetic radiation such as from mobile phones and base stations may promote cancer. Therefore, it was investigated experimentally, whether 900 MHz electromagnetic field exposure influences lymphoma development in a mouse strain that is genetically predisposed to this disease. The AKR/J mice genome carries the AK-virus, which leads within one year to spontaneous development of thymic lymphoblastic lymphoma.
320 unrestrained female mice were sham-exposed or exposed (each n = 160 animals) to GSM like 900 MHz electromagnetic fields for 24 hours per day, 7 days per week, at an average whole body specific absorption rate (SAR) value of 0.4 W/kg. Animals were visually checked daily and were weighed and palpated weekly. Starting with an age of 6 months, blood samples were taken monthly from the tail. Animals with signs of disease or with an age of about 46 weeks were sacrificed and a gross necropsy was performed.
Electromagnetic field exposure had a significant effect on body weight gain, with higher values in exposed than in sham-exposed animals. However, survival rate and lymphoma incidence did not differ between exposed and sham-exposed mice.
These data do not support the hypothesis that exposure to 900 MHz electromagnetic fields is a significant risk factor for developing lymphoma in a genetically predisposed species, even at a relatively high exposure level.
Objective
During the last decade, mobile phone use increased to almost 100% prevalence in many countries of the world. Evidence for potential health hazards accumulated in parallel by epidemiologic investigations has raised controversies about the appropriate interpretation and the degree of bias and confounding responsible for reduced or increased risk estimates.
Data Sources
Overall, I identified 33 epidemiologic studies in the peer-reviewed literature, most of which (25) were about brain tumors. Two groups have collected data for ≥ 10 years of mobile phone use: Hardell and colleagues from Sweden and the Interphone group, an international consortium from 13 countries coordinated by the International Agency for Research on Cancer.
Data Synthesis
Combined odds ratios (95% confidence intervals) from these studies for glioma, acoustic neuroma, and meningioma were 1.5 (1.2–1.8); 1.3 (0.95–1.9); and 1.1 (0.8–1.4), respectively.
Conclusions
Methodologic considerations revealed that three important conditions for epidemiologic studies to detect an increased risk are not met: a ) no evidence-based exposure metric is available; b) the observed duration of mobile phone use is generally still too low; c) no evidence-based selection of end points among the grossly different types of neoplasias is possible because of lack of etiologic hypotheses. Concerning risk estimates, selection bias, misclassification bias, and effects of the disease on mobile phone use could have reduced estimates, and recall bias may have led to spuriously increased risks. The overall evidence speaks in favor of an increased risk, but its magnitude cannot be assessed at present because of insufficient information on long-term use.
The widespread use of wireless telecommunications devices, particularly mobile phones and wireless networks, has resulted in increased human exposure to radiofrequency (RF) fields. Although national and international agencies have established safety guidelines for exposure to RF fields, concerns remain about the potential for adverse health outcomes to occur in relation to RF field exposure. The extensive literature on RF fields and health was reviewed by a number of authorities, including the Royal Society of Canada (1999)200.
Royal Society of Canada . A review of the potential health risks of radiofrequency fields from wireless telecommunication devices. Expert Panel Report, Publication No. RSC. EPR 99-1. Ottawa, Canada. 1999. View all references. This report is the third in a series of updates to the original report of the Royal Society of Canada, covering the period 2004–2007. In particular, the present study examined new data on (1) dosimetry and exposure assessment, (2) biological effects of RF fields such as enzyme induction, and (3) toxicological effects, including genotoxicity and carcinogenicity. Epidemiological studies of the potential health effects of RF exposure, particularly from mobile phones, were determined, along with human and animal studies of neurological and behavioural effects. Within the last 4 yrs investigators concluded that there is no clear evidence of adverse health effects associated with RF fields, although continued research is recommended to address specific areas of concern, including exposure to RF fields among children using mobile phones. The results of the ongoing 13-country World Health Organization INTERPHONE study of mobile phones may provide important new information on the potential cancer risks associated with mobile phone use.
Case-control studies have reported inconsistent findings regarding the association between mobile phone use and tumor risk. We investigated these associations using a meta-analysis.
We searched MEDLINE (PubMed), EMBASE, and the Cochrane Library in August 2008. Two evaluators independently reviewed and selected articles based on predetermined selection criteria.
Of 465 articles meeting our initial criteria, 23 case-control studies, which involved 37,916 participants (12,344 patient cases and 25,572 controls), were included in the final analyses. Compared with never or rarely having used a mobile phone, the odds ratio for overall use was 0.98 for malignant and benign tumors (95% CI, 0.89 to 1.07) in a random-effects meta-analysis of all 23 studies. However, a significant positive association (harmful effect) was observed in a random-effects meta-analysis of eight studies using blinding, whereas a significant negative association (protective effect) was observed in a fixed-effects meta-analysis of 15 studies not using blinding. Mobile phone use of 10 years or longer was associated with a risk of tumors in 13 studies reporting this association (odds ratio = 1.18; 95% CI, 1.04 to 1.34). Further, these findings were also observed in the subgroup analyses by methodologic quality of study. Blinding and methodologic quality of study were strongly associated with the research group.
The current study found that there is possible evidence linking mobile phone use to an increased risk of tumors from a meta-analysis of low-biased case-control studies. Prospective cohort studies providing a higher level of evidence are needed.
Mobile telecommunication technology became commercially available about 20-25 years ago in different countries around the world. The industry has grown exponentially over the years and, currently, the number of mobile phone users is estimated to be over 3.8 billion, more than half the world's population. Thus, because of such a large population-at-risk, any health hazard from these devices promises to have a large epidemiological impact. Intense speculation and investigation into the relationship between mobile phone usage and cancer has led to the publication of numerous, often contradictory, reports on this subject. This review aims to provide a large body of reported evidence to help medical professionals disseminate evidence-based information to their patients.
We recently reported an increased risk of uveal melanoma among mobile phone users. Here, we present the results of a case-control study that assessed the association between mobile phone use and risk of uveal melanoma. We recruited 459 uveal melanoma case patients at the University of Duisburg-Essen and matched 455 case patients with 827 population control subjects, 133 with 180 ophthalmologist control subjects, and 187 with 187 sibling control subjects. We used a questionnaire to assess mobile phone use and estimated odds ratios (ORs) and 95% confidence intervals (95% CIs) of risk for uveal melanoma using conditional logistic regression. Risk of uveal melanoma was not associated with regular mobile phone use (OR = 0.7, 95% CI = 0.5 to 1.0 vs population control subjects; OR = 1.1, 95% CI = 0.6 to 2.3 vs ophthalmologist control subjects; and OR = 1.2, 95% CI = 0.5 to 2.6 vs sibling control subjects), and we observed no trend for cumulative measures of exposure. We did not corroborate our previous results that showed an increased risk of uveal melanoma among regular mobile phone users.
The AKR mouse strain is characterized by a high incidence of spontaneous thymic lymphoma that appears in older animals (greater than 6 months of age) and is associated with novel provirus integrations of ecotropic and recombinant murine leukemia viruses (MuLVs). Treatment of 4- to 6-week-old AKR/J mice with the carcinogen N-methyl-N-nitrosourea (MNU) results in thymic lymphomas that arise as early as 3 to 4 months of age and contain novel somatically acquired MuLV provirus integrations. The AKR/J strain develops MNU-induced lymphoma with a higher incidence and shorter latency than has been observed for other inbred mouse strains. To determine whether provirus integrations of endogenous MuLV account for the enhanced susceptibility of the AKR strain, the incidence and latency of MNU-induced lymphoma development was compared in AKR/J and AKR.Fv-1b mice. The restrictive b allele of the Fv-1 locus restricts integration and replication of endogenous N-tropic MuLV; therefore, AKR-Fv-1b mice have a very low incidence of spontaneous lymphoma. In contrast, AKR.Fv-1b mice develop MNU-induced lymphomas with an incidence and latency similar to those of the AKR/J strain. Furthermore, thymic lymphomas from both strains express an immature CD4-8+ phenotype, indicating neoplastic transformation of the same thymocyte subset. Southern blot analysis confirmed that lymphoma DNA from AKR.Fv-1b mice did not contain somatically acquired provirus integrations. These results demonstrate that provirus integration does not contribute to the predisposition of AKR mice to develop a high incidence of early MNU-induced lymphomas. Nevertheless, MNU treatment stimulated high-level expression of infectious ecotropic MuLV in AKR.Fv-1b as well as in AKR/J mice, suggesting that viral gene products might enhance lymphoma progression.
Levels of DNA single-strand break were assayed in brain cells from rats acutely exposed to low-intensity 2450 MHz microwaves using an alkaline microgel electrophoresis method. Immediately after 2 h of exposure to pulsed (2 microseconds width, 500 pulses/s) microwaves, no significant effect was observed, whereas a dose rate-dependent [0.6 and 1.2 W/kg whole body specific absorption rate (SAR)] increase in DNA single-strand breaks was found in brain cells of rats at 4 h postexposure. Furthermore, in rats exposed for 2 h to continuous-wave 2450 MHz microwaves (SAR 1.2 W/kg), increases in brain cell DNA single-strand breaks were observed immediately as well as at 4 h postexposure.
In a 2-year bioassay, we exposed Fischer 344 rats to a frequency-modulated (FM) signal (836.55 MHz +/- 12.5 KHz deviation) simulating radiofrequency exposures in the head of users of hand-held mobile phones. We tested for effects on spontaneous tumorigenicity of central nervous system (CNS) tumors in the offspring of pregnant rats and also for modified incidence of primary CNS tumors in rats treated with a single dose of the neurocarcinogen ethylnitrosourea (ENU) in utero. ENU dosage (4 mg/kg) was selected to give an expected brain tumor incidence of 10-15% over the mean life span of 26 months. Pregnant dams (n = 102) were randomly assigned to six groups. Their offspring were treated as cohorts in each of the six groups (n = 90 per group; total, n = 540): Sham ENU/Sham Field, Sham ENU/Field Exposed, ENU/Sham Field, ENU/Field Exposed, ENU/Cage Control, and Sham ENU/Cage Control. Intermittent field exposures began on gestation day 19 and continued until weaning at 21 days, resuming thereafter at 31 days and continuing until experiment termination at 731-734 days. Energy absorption rates (SARs) in the rats' brains were similar to localized peak brain exposures of a phone user (female, 236 g, 1.0 W/kg; male, 450 g, 1.2 W/kg). Of the original 540 rats, 168 died before the termination of the experiment. In these rats, ENU significantly reduced survival from a mean of 708 days in three groups without ENU treatment to 645 days in three groups treated with ENU (P < 0.0005). There were no effects on survival attributable to FM field exposure in either ENU-treated or in sham-treated groups. Spontaneous CNS tumor incidence in control groups was 1.1-4.4% but sharply higher in rats receiving ENU (14.4-22.2%; P < 0.0001). No FM field-mediated changes were observed in number, incidence, or histological type of either spontaneous or ENU-induced brain tumors, nor were gender differences detected in tumor numbers. These negative findings with FM fields contrast with our study using standard digital phone fields pulsed on and off at 50/se, where a trend was noted toward reduced incidence of both spontaneous and ENU-induced CNS tumors (W. R. Adey et al., Radiat. Res., 152: 293-302, 1999). Although consistent but not attaining significance in the experiment overall (spontaneous CNS tumors, P < 0.08 one-tailed; P < 0.16 two-tailed; ENU-induced CNS tumors, P < 0.08 one-tailed, P < 0.16 two-tailed), the trend was significant (P < 0.015 one-tailed, P < 0.03, two-tailed) in rats that received ENU and died prior to experiment termination, with a primary brain tumor as the cause of death. We discuss differences in the signaling structure of digital and FM fields. Certain bioeffects induced by either amplitude-modulated or pulsed radiofrequency fields at athermal levels have not been seen with fields of similar average power but unvarying in intensity (continuous wave or frequency-modulated fields).
The influence of 2.45 GHz microwave (RF/MW) irradiation on blood-forming cells after whole-body irradiation of rats was investigated. The exposures were conducted with a field power density of 5-10 mW/cm2, and whole-body average specific absorption rate (SAR) of 1-2 W/kg. Four experimental subgroups were created and irradiated 2, 8, 15 or 30 days, for 2 h a day, 7 days a week. Concurrent sham-exposed rats were also included in the study. The cell response was assessed by number and type of the bone marrow nuclear cells and peripheral blood white cells using standard laboratory methods. Significant decrease in lymphoblast count was obtained at 15 and 30th experimental day (P < 0.05), whereas other examined parameters did not significantly differed in comparison to the sham-exposed controls. The findings point out at stress response in blood-forming system in rats after selected microwave exposure, which could be considered rather as sign of adaptation than malfunction.
Handheld mobile phones were introduced in Sweden during the late 1980s. The purpose of this population-based, case-control
study was to test the hypothesis that long-term mobile phone use increases the risk of brain tumors. The authors identified
all cases aged 20–69 years who were diagnosed with glioma or meningioma during 2000–2002 in certain parts of Sweden. Randomly
selected controls were stratified on age, gender, and residential area. Detailed information about mobile phone use was collected
from 371 (74%) glioma and 273 (85%) meningioma cases and 674 (71%) controls. For regular mobile phone use, the odds ratio
was 0.8 (95% confidence interval: 0.6, 1.0) for glioma and 0.7 (95% confidence interval: 0.5, 0.9) for meningioma. Similar
results were found for more than 10 years' duration of mobile phone use. No risk increase was found for ipsilateral phone
use for tumors located in the temporal and parietal lobes. Furthermore, the odds ratio did not increase, regardless of tumor
histology, type of phone, and amount of use. This study includes a large number of long-term mobile phone users, and the authors
conclude that the data do not support the hypothesis that mobile phone use is related to an increased risk of glioma or meningioma.
Disease relapse after allogeneic bone marrow transplantation (BMT) is a major cause of treatment failure and is thought to evolve from clinically occult residual disease in the recipient. However, the demonstration of minimal residual disease (MRD) in individual patients is of uncertain prognostic significance because the detection of residual disease has not consistently correlated with subsequent relapse. Moreover, the optimal therapeutic approach in patients with MRD after allogeneic BMT is unknown. The study of these issues has been hindered by the lack of clinically relevant animal models. In this report, we characterize a novel murine model for the study of MRD after allogeneic BMT. This model was designed to simulate high-risk BMT in humans in which patients receive transplants in relapse and disease recurrence in the major cause of treatment failure. The H-2-compatible, mixed lymphocyte culture nonreactive murine strains, AKR (H-2k) and CBA (H-2k), were chosen to parallel marrow transplants from HLA-matched siblings, which represent the majority of allo-transplants in humans. Male AKR leukemia cells were used in female donor/host chimeras permitting the Y chromosome to serve as a leukemia-specific marker for MRD. Detection of residual male leukemia cells in the peripheral blood of the primary host was facilitated by use of the polymerase chain reaction (PCR) and sequence-specific oligonucleotide probe hybridization (SSOPH). Use of PCR/SSOPH was highly predictive of clinical outcome (relapse or cure) in animals receiving transplants (P < .00002) and detected disease recurrence earlier than comparative flow cytometric analysis studies. This murine model will be useful in evaluating the efficacy of therapeutic strategies aimed at reducing disease relapse posttransplant and can be adapted to other transplant murine tumor systems for the study of MRD.
Statistical procedures underpin the process of scientific discovery. As researchers, one way we use these procedures is to test the validity of a null hypothesis. Often, we test the validity of more than one null hypothesis. If we fail to use an appropriate procedure to account for this multiplicity, then we are more likely to reach a wrong scientific conclusion-we are more likely to make a mistake. In physiology, experiments that involve multiple comparisons are common: of the original articles published in 1997 by the American Physiological Society, approximately 40% cite a multiple comparison procedure. In this review, I demonstrate the statistical issue embedded in multiple comparisons, and I summarize the philosophies of handling this issue. I also illustrate the three procedures-Newman-Keuls, Bonferroni, least significant difference-cited most often in my literature review; each of these procedures is of limited practical value. Last, I demonstrate the false discovery rate procedure, a promising development in multiple comparisons. The false discovery rate procedure may be the best practical solution to the problems of multiple comparisons that exist within physiology and other scientific disciplines.
Tables are provided which give the minimum sample sizes per treatment (or level) for all combinations of α = 0.5, 0.4, 0.3, 0.25, 0.2, 0.1, 0.05, 0.01 and β = 0.3, 0.2, 0.1, 0.05, for relative discrimination (Δ/σ) = 1.0(0.5)3.0, and for the number of fixed-effect treatments or factor levels t = 2(1)11, 13, 16, 21, 25, and 31. Relative discrimination is defined as a standardized difference Δ/σ, where Δ is the amount by which at least two of the treatments differ. Examples are given of experiments for which it is better to fix the Type II error rate β at a small value and allow the Type I error rate to become relatively large.
There is only one cause of failure in the proportional hazard model for identification of important prognostic factors, in which the covariates are assumed to be independent of time, that is, the event or failure is allowed to occur only once for each person, and there is no correlation among failure times of different persons. However, in practice, failure may be due to more than one event or cause, the same event or failure may recur during a follow-up study, and the event or failure time observed may be from related persons in a family or from the same person at different times. In this chapter we discuss several models for these situations. The first two models are extensions of the proportional hazards model to handle time-dependent covariates and to perform stratified analysis. Other models introduced in this chapter are for multiple causes of failure, recurrent events, and related observations. The chapter concludes with a problem solving section.
Sommer, A. M. and Lerchl, A. The Risk of Lymphoma in AKR/J Mice does not Rise with Chronic Exposure to 50 Hz Magnetic Fields (1 μT and 100 μT). Radiat. Res. 162, 194- 200 (2004). Some epidemiological studies suggest that exposure to 50 or 60 Hz magnetic fields might increase the risk of leukemia, especially in children with a comparable high residential exposure. To investigate this possibility experimentally, the influence of 50 Hz magnetic-field exposure on lymphoma induction was determined in a mouse strain that is genetically predisposed to this disease. The AKR/J mouse genome carries the AK virus, which leads within 1 year to spontaneous development of thymic lymphoblastic lymphoma. Beginning at an age of 4-5 weeks, groups of 160 female mice were sham-exposed or exposed to 50 Hz magnetic fields at 1 or 100 μT for 24 h per day, 7 days per week, for 38 weeks. Animals were checked visually daily and were weighed and palpated weekly. There was no effect of magnetic-field exposure on body weight gain or survival rate, and lymphoma incidence did not differ between exposed and sham-exposed animals. Therefore, these data do not support the hypothesis that chronic exposure to 50 Hz magnetic fields is a significant risk factor for developing hematopoietic malignancy.
The present study aimed to investigate the effects of microwaves (MW) emitted by cellular phones (CPs) on peripheral blood parameters and birth weights of rats. Thirty-six albino rats were divided into four groups, male (n = 6) and female sham-exposed groups (n = 12) and male (n = 6) and female experimental groups (n = 12). No blood parameters differed following exposure (p > 0.05). The birth weight of offspring in the experimental group was significantly lower than in the sham-exposed group (p < 0.001). No significant differences were observed between rectal temperatures of rats in the sham and experimental groups (p > 0.05). The specific absorption rate (SAR) was found to be 0.155 W/kg for the experimental groups. All parameters investigated were normal in the next generation of rats (p > 0.05).
Whether radiofrequency (RF) fields are carcinogenic is controversial; epidemiological data have been inconclusive and animal tests limited. The aim of the present study was to determine whether long-term exposure to pulse-modulated RF fields similar to those used in digital mobile telecommunications would increase the incidence of lymphoma in E mu-Pim1 transgenic mice, which are moderately predisposed to develop lymphoma spontaneously. One hundred female E mu-Pim1 mice were sham-exposed and 101 were exposed for two 30-min periods per day for up to 18 months to plane-wave fields of 900 MHz with a pulse repetition frequency of 217 Hz and a pulse width of 0.6 ms. Incident power densities were 2.6-13 W/m2 and specific absorption rates were 0.008-4.2 W/kg, averaging 0.13-1.4 W/kg. Lymphoma risk was found to be significantly higher in the exposed mice than in the controls (OR = 2.4. P = 0.006, 95% CI = 1.3-4.5). Follicular lymphomas were the major contributor to the increased tumor incidence. Thus long-term intermittent exposure to RF fields can enhance the probability that mice carrying a lymphomagenic oncogene will develop lymphomas. We suggest that such genetically cancer-prone mice provide an experimental system for more detailed assessment of dose-response relationships for risk of cancer after RF-field exposure.
In lifetesting, medical follow-up, and other fields the observation of the time of occurrence of the event of interest (called a death) may be prevented for some of the items of the sample by the previous occurrence of some other event (called a loss). Losses may be either accidental or controlled, the latter resulting from a decision to terminate certain observations. In either case it is usually assumed in this paper that the lifetime (age at death) is independent of the potential loss time; in practice this assumption deserves careful scrutiny. Despite the resulting incompleteness of the data, it is desired to estimate the proportion P(t) of items in the population whose lifetimes would exceed t (in the absence of such losses), without making any assumption about the form of the function P(t). The observation for each item of a suitable initial event, marking the beginning of its lifetime, is presupposed.
For random samples of size N the product-limit (PL) estimate can be defined as follows: List and label the N observed lifetimes (whether to death or loss) in order of increasing magnitude, so that one has Then , where r assumes those values for which and for which measures the time to death. This estimate is the distribution, unrestricted as to form, which maximizes the likelihood of the observations.
Other estimates that are discussed are the actuarial estimates (which are also products, but with the number of factors usually reduced by grouping); and reduced-sample (RS) estimates, which require that losses not be accidental, so that the limits of observation (potential loss times) are known even for those items whose deaths are observed. When no losses occur at ages less than t the estimate of P(t) in all cases reduces to the usual binomial estimate, namely, the observed proportion of survivors.
The present study was conducted to investigate the possible effect of 60 Hz circularly polarized magnetic fields (MFs) as promoters of genetically initiated lymphoma in AKR mice. One hundred sixty female animals were divided into four different groups. They were exposed to four different intensities of circularly polarized MFs. Animals received exposure to 60 Hz circularly polarized MF at field strengths (rms-value) of 0 microT (sham control, T1, Group I), 5 microT(T2, Group II), 83.3 microT (T3, Group III), or 500 microT(T4, Group IV), for 21 h/day from the age of 4-6 weeks to the age of 44-46 weeks. There were no exposure-related changes in mean survival time, clinical signs, body weights, hematological values, micronucleus assay, gene expression arrays, analysis of apoptosis, and necropsy findings. At histopathological examination, lymphoma was seen in all the groups. The tumor incidence was 31/40(78%), 30/40(75%), 32/40(80%), and 31/40(78%) in sham control, 5, 83.3, and 500 microT groups, respectively. However, there were no differences in the tumor incidence between the sham control (T1) and circularly polarized MF exposure groups (T2-T4). In conclusion, there was no evidence that exposure to 60 Hz circularly polarized MF strengths up to 500 microT promoted lymphoma in AKR mice.
AKR mice are highly susceptible to spontaneous T cell lymphomagenesis and thymus removal at the age of 1 to 3 mo greatly reduces its development. Twelve-mo-old AKR mice thymectomized at young age were shown previously to carry potential lymphoma cells that could be triggered to develop into B cell lymphomas (80 to 100%) after removal from their host "restrictive" environment into young histocompatible hosts. Additional attempts were made to terminate the potential lymphoma cell dormant state in 12-mo-old thymectomized AKR mice. Replenishment of some deficiencies caused by thymectomy at a young age, including a s.c. syngeneic thymus graft or a single injection of the dual tropic recombinant virus isolates DTV-71 or MCF-247 into 12-mo-old thymectomized AKR mice resulted in Ly-1+ pre-B or B cell lymphoma development in 80 to 98% of these treated mice. In vivo elimination of T cell subsets by administration of cyclosporin A or by mAb expressed on Th cells (anti-CD4) or cytotoxic T cells (anti-CD8) stimulated the progression of dormant potential lymphoma cells towards B cell lymphoma development. The most striking results were observed after administration of anti-CD8 mAb: 90 to 100% of these treated mice developed Ly-1+ B cell lymphomas within 80 days. The effect of rIL-2 on dormant PLC was also tested. Administration of rIL-2 to 12-mo-old thymectomized mice terminated tumor dormancy in 94% of the treated mice within 66 days. Tests of the resulting B lymphomas for dual tropic recombinant virus/mink cell focus-inducing virus infection indicated that the breakdown of tumor dormancy did not result from development of pathogenic class I mink cell focus-inducing viruses. These results suggest that T cell subsets and/or their products are involved in the proliferation arrest of potential lymphoma cells present in thymectomized AKR mice.
Restriction of energy intake significantly reduces mammary tumorigenesis in normal rats exposed to carcinogens. Genetically obese LA/N-cp (corpulent) female rats were given 7,12-dimethylbenz[a]anthracene and fed purified diets ad libitum or restricted to 60% of the ad libitum caloric intake. Phenotypically lean littermates were also fed ad libitum. Obese animals developed large mammary tumors more rapidly than genetically normal rats so that 100% of the animals had tumors in less than 16 weeks. Only 21% of the lean animals developed tumors; the energy restricted obese animals had a tumor incidence of 27%. Although obese rats fed the restricted diet weighed significantly less than those fed ad libitum, percent body fat was not reduced, indicating that lean tissue was affected more. Obese animals were markedly hyperinsulinemic (1003 +/- 193 microunits/ml) and energy restriction reduced this to 328 +/- 41; the lean animals had insulin levels of 12 +/- 2. Tumor-bearing rats had higher insulin levels than rats without tumors. These data suggest that body fatness is not directly associated with risk of carcinogenesis. Lean body mass, adipose tissue mass, and their interaction with insulin in its capacity as a growth factor rather than body fatness per se may be determinants of tumor promotion.
Treatment of young AKR/J mice with N-methyl-N-nitrosourea (MNU) results in the induction of a high incidence of thymic lymphomas occurring between 4 and 6 months of age. The tumor incidence is higher and the latency period is shorter than that observed in other MNU-treated mouse strains. Analysis of tumor incidence in crosses of AKR/J with C57L/J mice indicates that several genes influence the incidence and latency of MNU-induced thymic lymphomas. One of these genes appears to be tightly linked to the albino locus of chromosome 7.
Mammary tumors were induced by 7,12-dimethylbenz[a]anthracene (DMBA) in Sprague-Dawley female rats kept under different dietary restrictions. Starting at 40 days of age, 4 groups of rats were either full-fed or fed 25%, 50% or 80% of their daily ration. At 55 days of age DMBA was given by intravenous injection. Rats were continued on the restricted diet until 150 days after carcinogen treatment. Rats on 25% diet lost weight rapidly and the experiment had to be terminated. Rats on the 50% diet maintained a lower body weight throughout the experiment; only 12% developed tumors. Rats on the 80% diet lost weight initially, but at the termination of the experiment, there was no significant difference in body weight between this group and the full-fed controls. Of the rats on 80% diet, 34% developed tumors, compared to 92% tumor incidence in the full-fed controls. Vaginal smears were normal in the animals fed the 80% diet, while some irregularity was observed in the 50% group. Breeding capability in rats on the 80% diet was not affected, since there was no observable difference in the pregnancy rate between these animals and their controls. There was also no difference in plasma level of estrogen between the 80% diet group and the full-fed controls at the time of carcinogen treatment. [3H]Thymidine labelling index was significantly affected by 50% restriction of diet while there was no significant change in the 80% group.
Strain RFM mice were exposed to 800 MHz radiofrequency radiation at an average incident power level of 43 mW/cm2 2 hr/day, 5 days/week, for 35 weeks. Observations on peripheral blood, body weight, voluntary activity and mean life span revealed no decrement attributable to r.f. exposure. (C)1971Health Physics Society
Mice were exposed in the far field in an anechoic chamber to 2,880-MHz pulsed microwaves 3 to 7.5 h daily, 5 days/week for 60 to 360 h. Three experiments were performed at average power densities of 5 mW/cm2 and six at 10 mW/cm2, corresponding to averaged specific absorption rates (SARs) of 2.25 and 4.50 mW/g, respectively. Each experiment consisted of eight mice, with a concurrently sham-exposed group of eight. In two of three studies at 5 mW/cm2, there was a significant increase in bone marrow cellularity in the microwave-exposed groups compared to the sham-exposed groups. Significant differences were occasionally seen in erythrocyte, leukocyte, and platelet values from microwave-exposed groups, but were not consistently observed. In one of six groups exposed at 10 mW/cm2, mean bone marrow cellularity was reduced significantly in the microwave-exposed mice; in another group, the lymphocyte count was increased. In only one exposure (10 mW/cm2 for 360 h) was any significant effect noted on serum proteins: a reduction to 5.1 +/- 0.3 g/dl in the exposed versus 5.6 +/- 0.4 g/dl in the sham-exposed mice. This was due to a decrease in alpha and beta globulins, with no effect on albumin or gamma globulin concentrations. No effect on bone marrow granulocyte/macrophage colony-forming units (CFU) was revealed following exposure of mice to pulsed microwaves at 5 mW/cm2. In one of four exposures at 10 mW/cm2, there was a significant increase in CFU-agar colonies. No significant effects of exposures at 10 mW/cm2 were observed on in vivo and in vitro assays of cell-mediated immune functions. No exposure-related histopathologic lesions were found from examination of several tissues and organs. Results of these series of exposures of mice at SARs of 2.25 and 4.50 mW/g indicated no consistent effects on the hematologic, immunologic, or histopathologic variables examined.
Growth of syngeneic P815 mastocytoma in DBA/2J male mice was evaluated following social and physical stress exposure. Although social isolation following tumor cell transplantation enhanced tumor growth, it appeared that it was the abrupt change in social conditions, rather than the isolation per se which was responsible for the exacerbation of tumorigenicity. Moreover, it was found that the animals' behavior after social change could modify this effect. If mice engaged in persistent fighting, the tumorigenic consequences of social change were not apparent. In addition, it was observed that social conditions interacted with physical stress. Footshock enhanced tumor growth among group housed mice, but retarded tumor development among socially isolated mice.
Disease relapse after allogeneic bone marrow transplantation (BMT) is a major cause of treatment failure and is thought to evolve from clinically occult residual disease in the recipient. However, the demonstration of minimal residual disease (MRD) in individual patients is of uncertain prognostic significance because the detection of residual disease has not consistently correlated with subsequent relapse. Moreover, the optimal therapeutic approach in patients with MRD after allogeneic BMT is unknown. The study of these issues has been hindered by the lack of clinically relevant animal models. In this report, we characterize a novel murine model for the study of MRD after allogeneic BMT. This model was designed to simulate high-risk BMT in humans in which patients receive transplants in relapse and disease recurrence in the major cause of treatment failure. The H-2-compatible, mixed lymphocyte culture nonreactive murine strains, AKR (H-2k) and CBA (H-2k), were chosen to parallel marrow transplants from HLA-matched siblings, which represent the majority of allo-transplants in humans. Male AKR leukemia cells were used in female donor/host chimeras permitting the Y chromosome to serve as a leukemia-specific marker for MRD. Detection of residual male leukemia cells in the peripheral blood of the primary host was facilitated by use of the polymerase chain reaction (PCR) and sequence-specific oligonucleotide probe hybridization (SSOPH). Use of PCR/SSOPH was highly predictive of clinical outcome (relapse or cure) in animals receiving transplants (P < .00002) and detected disease recurrence earlier than comparative flow cytometric analysis studies. This murine model will be useful in evaluating the efficacy of therapeutic strategies aimed at reducing disease relapse posttransplant and can be adapted to other transplant murine tumor systems for the study of MRD.
A study of the effect of sodium nitrite (SN) on leukemia development in mice induced by Rauscher Leukemia virus (RLV) (Balb/c mice), Mazurenko leukemia virus (MaLV) (CC57Br mice), and Gross leukemia virus (GLV) (AKR/J mice) was performed. SN was administered in water (at concentrations of 5.0, 50.0, 500.0, and 2000.0 mg/l, by NaNO2). A moderate, yet statistically significant acceleration of leukemia development was observed in some groups of SN-treated mice. Our findings and the literature provide evidence that SN has the capacity to enhance the carcinogenic effect of leukemia viruses in vivo.
We conducted a meta-analysis to acquire an understanding of the association between leukemia and occupational exposure to electric and magnetic fields. To explore sources of heterogeneity, study characteristics were scored and examined using regression analysis. While most studies present a small elevation in risk, the apparent lack of a clear pattern of exposure to EMF and risk of leukemia substantially detracts from the hypothesis that measured magnetic fields in the work environment are responsible for the observed excess risk of leukemia. Findings were not sensitive to assumptions, influence of individual studies, weighting schemes, and modeling. Some evidence of publication bias is noted.
1. A common statistical flaw in articles submitted to or published in biomedical research journals is to test multiple null hypotheses that originate from the results of a single experiment without correcting for the inflated risk of type 1 error (false positive statistical inference) that results from this. Multiple comparison procedures (MCP) are designed to minimize this risk. The present review focuses on pairwise contrasts, the most common sort of multiple comparisons made by biomedical investigators. 2. In an earlier review a variety of MCP were described and evaluated. It was concluded that an effective MCP should control the risk of family-wise type 1 error, so as to ensure that not more than one hypothesis within a single family is falsely rejected. One-step procedures based on the Bonferroni or Sidák inequalities do this. For continuous data and under normal distribution theory, so does the Tukey-Kramer procedure for all possible pairwise contrasts of means and the Dunnett procedure for all possible pairwise contrasts of means with a control mean. 3. There is now a new class of MCP, based on the Bonferroni or Sidák inequalities but performed in a step-wise fashion. The members of this class have certain desirable properties. They: (i) control the family-wise type 1 error rate as effectively as the one-step procedures; (ii) are more powerful than the one-step Bonferroni or Sidák procedures, especially when hypotheses are logically related; and (iii) can be applied not only to continuous data but also to ordinal or categorical data. 4. Of the new step-wise MCP, Holm's step-down procedures are commended for their combination of accuracy, power and versatility. They also have the virtue of simplicity. Given the raw P values that result from conventional tests of significance, the adjustments for multiple comparisons can be made by hand or hand-held calculator. 5. Despite the corrective abilities of the new step-wise MCP, investigators should try to design their experiments and analyses to test a single, global hypothesis rather than multiple ones.
A weak association between residential or occupational exposure to electric and magnetic fields (50/60 Hz fields) and an increased incidence of leukemia has been reported. Numerous animal studies have evaluated the potential association between magnetic-field exposure and leukemia. These include long-term (up to 2(1/2) years) bioassays, initiation/promotion studies, investigations in transgenic models, and tumor growth studies. Exposure to 60 Hz circularly polarized magnetic fields at 1,400 microT for 28 months did not affect lymphoma incidence in mice. The study included over 2000 C57BL/6J mice. In another study, 1000 B6C3F(1) mice exposed to 60 Hz magnetic fields up to 1000 microT for 2 years showed no increase in lymphomas. Approximately 400 transgenic Emu-Pim1 mice exposed to 50 Hz fields up to 1000 microT for up to 18 months had no increased incidence of leukemia. Similarly, Trp53(+/-) mice and Pim1transgenic mice exposed to 60 Hz magnetic fields for 23 weeks showed no increased incidence of lymphoma. Three studies in F344 rats exposed to 50 or 60 Hz magnetic fields up to 5 mT showed no increased incidence of leukemia. The combined animal bioassay results are nearly uniformly negative for magnetic-field exposures enhancing leukemia and weaken the possible epidemiological association between magnetic-field exposures and leukemia in humans as suggested by epidemiological data.
Exposure limits set for microwave radiation assume that any biological
effects result from tissue heating1: non-thermal effects have
been reported but remain controversial. We show here that prolonged exposure
to low-intensity microwave fields can induce heat-shock responses in the soil
nematode Caenorhabditis elegans. This effect appears to be non-thermal,
suggesting that current exposure limits set for microwave equipment may need
to be reconsidered.
Increasing applications of electromagnetic fields are of great concern with regard to public health. Several in vitro studies have been conducted to detect effects of microwave exposure on the genetic material leading to negative or questionable results. The micronucleus (MN) assay which is proved to be a useful tool for the detection of radiation exposure-induced cytogenetic damage was used in the present study to investigate the genotoxic effect of microwaves in human peripheral blood lymphocytes in vitro exposed in G(0) to electromagnetic fields with different frequencies (2.45 and 7.7GHz) and power density (10, 20 and 30mW/cm(2)) for three times (15, 30 and 60min). The results showed for both radiation frequencies an induction of micronuclei as compared to the control cultures at a power density of 30mW/cm(2) and after an exposure of 30 and 60min. Our study would indicate that microwaves are able to cause cytogenetic damage in human lymphocytes mainly for both high power density and long exposure time.
It has been suggested that chronic, low-level exposure to radiofrequency (RF) radiation may promote the formation of tumors. Previous studies, however, showed that low-level, long-term exposure of mammary tumor-prone mice to 435 MHz or 2450 MHz RF radiation did not affect the incidence of mammary tumors. In this study, we investigated the effects of exposure to a unique type of electromagnetic energy: pulses composed of an ultra-wideband (UWB) of frequencies, including those in the RF range. One hundred C3H/HeJ mice were exposed to UWB pulses (rise time 176 ps, fall time 3.5 ns, pulse width 1.9 ns, peak E-field 40 kV/m, repetition rate 1 kHz). Each animal was exposed for 2 min once a week for 12 weeks. One hundred mice were used as sham controls. There were no significant differences between groups with respect to incidence of palpated mammary tumors, latency to tumor onset, rate of tumor growth, or animal survival. Histopathological evaluations revealed no significant differences between the two groups in numbers of neoplasms in all tissues studied (lymphoreticular tissue, thymus, respiratory, digestive and urinary tracts, reproductive, mammary and endocrine systems, and skin). Our major finding was the lack of effects of UWB-pulse exposure on promotion of mammary tumors in a well-established animal model of mammary cancer.
The effects of 1.5 GHz electromagnetic near fields of time division multiple access (TDMA) signal for the Personal Digital Cellular, Japanese cellular telephone standard (PDC) used for cellular phones, on mouse skin carcinogenesis initiated by 7,12-dimethylbenz[a]anthracene (DMBA) were examined. Ten-week-old ICR female mice were treated with a single application of DMBA on shaved dorsal skin by painting at a concentration of 100 microg/100 microl acetone per mouse. One week later, mice were divided into four groups, receiving electromagnetic near fields exposure (DMBA-EMF), sham-exposure (DMBA-Sham), 12-O-tetradecanoylphorbol-13-acetate (TPA, 4 microg /200 microl acetone/mouse), as a positive control (DMBA-TPA), and no-treatment (DMBA-Control). EMF near fields exposure conditions were as follows: skin local peak specific absorption rate (SAR) 2.0 W/kg, whole body average SAR 0.084 W/kg (ratio of peak to average SAR is 24), 90 min a day, 5 days a week, for 19 weeks. At week 20, animals were killed and skin tumors were analyzed histopathologically. The incidences of skin tumors in DMBA-EMF, DMBA-Sham, DMBA-TPA and DMBA-Control groups were 0/48 (0%), 0/48 (0%), 29/30 (96.6%) and 1/30 (3.3%), respectively. Histopathologically, papilloma and squamous cell carcinoma (SCC) were observed in the DMBA-TPA group and only papilloma observed in the DMBA-Control group. The incidences of squamous cell papillomas and squamous cell carcinomas in DMBA-TPA and DMBA-Control groups were 29/30 (96.6%) and 1/30 (3.3%), respectively, numbers of tumors per mouse (tumor multiplicity) being 18.8 +/- 13.4 and 0.1 +/- 0.5. These data clearly demonstrated that near fields exposure to 1.5 GHz EMF, used for cellular phones, does not exert any enhancing effect on skin tumorigenesis initiated by DMBA.
A case-control study on brain tumours included 233 patients aged 20-80 years and alive at the study time. They had histopathologically verified brain tumour and lived in the Uppsala-Orebro region (1994-1996) or the Stockholm region (1995-1996). Two matched controls to each case were selected from the Swedish Population Register. Two hundred and nine cases (90%) and 425 controls (91%) answered the questionnaire. Results are presented for the whole study group, as given here, and for malignant and benign tumours separately. For workers in the chemical industry the odds ratio (OR) was 4.10, 95% confidence interval (95% CI) 1.25-13.4 and laboratory workers OR 3.21, 95% CI 1.16-8.85. Radiotherapy of the head and neck region gave OR 3.61, 95% CI 0.65-19.9. Medical diagnostic X-ray of the same area yielded OR 1.64, 95% CI 1.04-2.58. Work as a physician gave OR 6.00, 95% CI 0.62-57.7. All three cases had worked with fluoroscopy. Ipsilateral (same side) use of a cellular telephone increased the risk of tumours in the temporal, temporoparietal and occipital areas, with OR 2.42, 95% CI 0.97-6.05 (i.e. the anatomical areas with highest exposure to microwaves from a mobile phone).
A total of 120 E mu-Pim1 heterozygous mice and 120 wild-type mice were exposed for 1 h/day 5 days/week at each of the four exposure levels in "Ferris-wheel" exposure systems for up to 104 weeks to GSM-modulated 898.4 MHz radiation at SARs of 0.25, 1.0, 2.0 and 4.0 W/kg. In addition, 120 heterozygous and 120 wild-type mice were sham-exposed; there was also an unrestrained negative control group. Four exposure levels were used to investigate whether a dose-response effect could be detected. Independent verification confirmed that the exposures in the current study were nonthermal. There was no significant difference in the incidence of lymphomas between exposed and sham-exposed groups at any of the exposure levels. A dose-response effect was not detected. The findings showed that long-term exposures of lymphoma-prone mice to 898.4 MHz GSM radiofrequency (RF) radiation at SARs of 0.25, 1.0, 2.0 and 4.0 W/kg had no significant effects when compared to sham-irradiated animals. A previous study (Repacholi et al., Radiat. Res. 147, 631-640, 1997) reported that long-term exposure of lymphoma-prone mice to one exposure level of 900 MHz RF radiation significantly increased the incidence of non-lymphoblastic lymphomas when compared to sham-irradiated animals.
Whether exposure to radiation emitted from cellular phones poses a health hazard is at the focus of current debate. We have examined whether in vitro exposure of human peripheral blood lymphocytes (PBL) to continuous 830 MHz electromagnetic fields causes losses and gains of chromosomes (aneuploidy), a major "somatic mutation" leading to genomic instability and thereby to cancer. PBL were irradiated at different average absorption rates (SAR) in the range of 1.6-8.8 W/kg for 72 hr in an exposure system based on a parallel plate resonator at temperatures ranging from 34.5-37.5 degrees C. The averaged SAR and its distribution in the exposed tissue culture flask were determined by combining measurements and numerical analysis based on a finite element simulation code. A linear increase in chromosome 17 aneuploidy was observed as a function of the SAR value, demonstrating that this radiation has a genotoxic effect. The SAR dependent aneuploidy was accompanied by an abnormal mode of replication of the chromosome 17 region engaged in segregation (repetitive DNA arrays associated with the centromere), suggesting that epigenetic alterations are involved in the SAR dependent genetic toxicity. Control experiments (i.e., without any RF radiation) carried out in the temperature range of 34.5-38.5 degrees C showed that elevated temperature is not associated with either the genetic or epigenetic alterations observed following RF radiation-the increased levels of aneuploidy and the modification in replication of the centromeric DNA arrays. These findings indicate that the genotoxic effect of the electromagnetic radiation is elicited via a non-thermal pathway. Moreover, the fact that aneuploidy is a phenomenon known to increase the risk for cancer, should be taken into consideration in future evaluation of exposure guidelines.
This study was designed to determine whether chronic exposure to radiofrequency (RF) radiation from cellular phones increased the incidence of spontaneous tumors in F344 rats. Eighty male and 80 female rats were randomly placed in each of three irradiation groups. The sham group received no irradiation; the Frequency Division Multiple Access (FDMA) group was exposed to 835.62 MHz FDMA RF radiation; and the Code Division Multiple Access (CDMA) group was exposed to 847.74 MHz CDMA RF radiation. Rats were irradiated 4 h per day, 5 days per week over 2 years. The nominal time-averaged specific absorption rate (SAR) in the brain for the irradiated animals was 0.85 +/- 0.34 W/kg (mean +/- SD) per time-averaged watt of antenna power. Antennas were driven with a time-averaged power of 1.50 +/- 0.25 W (range). That is, the nominal time-averaged brain SAR was 1.3 +/- 0.5 W/kg (mean +/- SD). This number was an average from several measurement locations inside the brain, and it takes into account changes in animal weight and head position during irradiation. All major organs were evaluated grossly and histologically. The number of tumors, tumor types and incidence of hyperplasia for each organ were recorded. There were no significant differences among final body weights or survival days for either males or females in any group. No significant differences were found between treated and sham-exposed animals for any tumor in any organ. We conclude that chronic exposure to 835.62 MHz FDMA or 847.74 MHz CDMA RF radiation had no significant effect on the incidence of spontaneous tumors in F344 rats.
This article is a review of the effects of radiofrequency (RF) energy on (1). survival and (2). cancer in the same animal populations having survival data. The literature consisted of 18 studies with survival data, and 16 of these have information on cancer. In one study, a significant decrease in lifespan was observed at 6.8 W/kg but not at 2 W/kg. Thermal stress appears to be the causal factor for the effect on lifespan because the higher dose rate, unlike the lower dose rate, was estimated to increase body temperature significantly. The finding that the lower level was without effect is consistent with the results of a number of recent studies showing that long term, low level exposure to RF energy did not affect survival adversely. Many of these recent studies addressed the cancer issue by histopathological analysis of many organs and tissues following exposure up to 2 years, the average lifetime of rats and mice. Some investigations examined the effect of RF fields from mobile phones on brain cancer, including the progression of chemically induced brain cancer. The results demonstrate that RF exposure did not adversely affect cancer incidence at whole body specific absorption rates (SARs) <or=4 W/kg and brain SARs <or=2.3 W/kg. The weight-of-evidence of these 18 studies shows that long term, low level exposure to RF energy does not adversely affect survival and cancer in laboratory mammals.
This report outlines the characteristics of universal mobile telecommunications system (UMTS) signals and discusses the signal parameters with respect to their possible biological relevance in order to define a generic UMTS test signal (GUS) for experiments aiming at the investigation of biological effects of weak electromagnetic fields. The GUS includes features of a real UMTS signal and especially the characteristics of UMTS, which differ from those of already applied second generation mobile communication systems (GSM 900, DCS1800, PCS1900, IS-95). It has been specified on the basis of the recommendations of a working group of the German Forschungsgemeinschaft Funk (FGF) with a focus on the mechanisms of UMTS which are responsible for slow term signal contributions, i.e., low frequency variations of the radio frequency (RF) envelope, since the hypothetical possibility of biological relevance of weak electromagnetic fields is often attributed to time variations of the RF envelope with frequencies close to those of natural processes. In this respect, it is also shown that the mandatory power control loop in UMTS gives rise to very strong 1.5 kHz variations on the air interface. Based upon the concept of the GUS, a UMTS test signal generator (GUS6960S) is described.
The purpose of this study was to observe the erythropoietic changes in rats subchronically exposed to radiofrequency microwave (RF/MW) irradiation at nonthermal level. Adult male Wistar rats (N=40) were exposed to 2.45 GHz continuous RF/MW fields for 2 hours daily, 7 days a week, at 5-10 mW/cm2. Exposed animals were divided into four subgroups (n=10 animals in each subgroup) in order to be irradiated for 2, 8, 15 and 30 days. Animals were sacrified on the final irradiation day of each treated subgroup. Unexposed rats were used as control (N=24). Six animals were included into the each control subgroup. Bone marrow smears were examined to determine absolute counts of anuclear cells and erythropoietic precursor cells. The absolute erythrocyte count, haemoglobin and haematocrit values were observed in the peripheral blood by an automatic cell counter. The bone marrow cytogenetic analysis was accomplished by micronucleus (MN) tests. In the exposed animals erythrocyte count, haemoglobin and haematocrit were increased in peripheral blood on irradiation days 8 and 15. Concurrently, anuclear cells and erythropoietic precursor cells were significantly decreased (p < 0.05) in the bone marrow on day 15, but micronucleated cells' frequency was increased. In the applied experimental condition, RF/MW radiation might cause disturbance in red cell maturation and proliferation, and induce micronucleus formation in erythropoietic cells.