In vivo genotoxicity of high-intensity intermediate frequency magnetic fields in somatic cells and germ cells.

Intermediate frequency magnetic fields (IF-MFs) at ~85 kHz are one of the components of wireless power transfer (WPT) systems. However, the available data needed for the assessment of the safety of organisms from IF-MF exposure are scarce. Thus, there is an imminent need to accumulate evidence-based assessment data. In particular, if humans are exposed to IF-MF due to an accident or trouble, they are at increased risk of being exposed to high-intensity IF-MF within a short period. The already existing exposure system was improved to a system that could intermittently expose animals at 3 s intervals. This system allows the exposure of a mouse to high-intensity IF-MF (frequency: 82.3 kHz; induced electric field: 87 V/m, which was 3.8 times the basic restriction level for occupational exposure in the ICNIRP guideline), while regulating the heat generated by the coil. In vivo genotoxicity after IF-MF exposure was assessed using micronucleus (MN) test, Pig-a assay, and gpt assay. The results of MN test and Pig-a assay in hematopoietic cells revealed that neither the reticulocytes nor the mature erythrocytes exhibited significant increases in the IF-MF-exposed group compared with that in the sham-exposed group. In germ cells, MN test and gpt assay outcomes showed that IF-MF exposure did not cause any genetic or chromosomal abnormality. Based on these data, there was no genotoxic effect of our set IF-MF exposure on somatic and germ cells. These findings can contribute to the widespread use of WPT systems as effective data of IF-MF safety assessment.

Cataract Formation by Near-infrared Radiation in Rabbits.

Surveys and epidemiological studies have shown an increased prevalence of cataracts in workers in the glass and steel industries. These cataracts are associated with exposure to intense infrared radiation (IR) emitted from heated materials and industrial furnaces. Thermal model calculations predicted that near and far IR would cause cataract with different mechanisms. The present study investigated cataract formation by near IR. Eyes of pigmented rabbits were exposed to IR at a wavelength of 808 nm. Morphological changes in the anterior segment of the eye were assessed by slit-lamp microscopy, and temperature distributions in the anterior chamber of the eye were observed during IR exposure using microencapsulated thermochromic liquid crystals. Cortical cataract appeared below the exposed area of the iris in eyes that had been exposed for 6 min to an irradiance of 1.27 W cm-2 or higher. The monitored temperature in the anterior chamber began to increase in the region adjacent to the exposed area of the iris with the onset of IR exposure. These results demonstrate that 808-nm IR is absorbed and converted to heat within the iris, which is then conducted to the lens and produce a cataract, as Goldmann theory states.

Long-term exposure to a 40-GHz electromagnetic field does not affect genotoxicity or heat shock protein expression in HCE-T or SRA01/04 cells.

Millimeter waves are used in various fields, and the risks of this wavelength range for human health must be carefully evaluated. In this study, we investigated the effects of millimeter waves on genotoxicity and heat shock protein expression in human corneal epithelial (HCE-T) and human lens epithelial (SRA01/04) cells. We exposed the cells to 40-GHz millimeter waves at 1 mW/cm2 for 24 h. We observed no statistically significant increase in the micronucleus (MN) frequency or the level of DNA strand breaks in cells exposed to 40-GHz millimeter waves relative to sham-exposed and incubator controls. Heat shock protein (Hsp) expression also exhibited no statistically significant response to the 40-GHz exposure. These results indicate that exposure to 40 GHz millimeter waves under these conditions has little or no effect on MN formation, DNA strand breaks, or Hsp expression in HCE-T or SRA01/04 cells.

Effects of Long-Term Exposure to 60 GHz Millimeter-Wavelength Radiation on the Genotoxicity and Heat Shock Protein (Hsp) Expression of Cells Derived from Human Eye.

Human corneal epithelial (HCE-T) and human lens epithelial (SRA01/04) cells derived from the human eye were exposed to 60 gigahertz (GHz) millimeter-wavelength radiation for 24 h. There was no statistically significant increase in the micronucleus (MN) frequency in cells exposed to 60 GHz millimeter-wavelength radiation at 1 mW/cm² compared with sham-exposed controls and incubator controls. The MN frequency of cells treated with bleomycin for 1 h provided positive controls. The comet assay, used to detect DNA strand breaks, and heat shock protein (Hsp) expression also showed no statistically significant effects of exposure. These results indicate that exposure to millimeter-wavelength radiation has no effect on genotoxicity in human eye cells.

Cerebral glucose metabolism in the striate cortex positively correlates with fractional anisotropy values of the optic radiation in patients with glaucoma.

BACKGROUND: It has recently become clear that glaucoma is not only an ocular disease, but involves central visual pathways as well. The purpose of this study was to examine functional and structural alterations in the brains of glaucoma patients. DESIGN: Case-control study in a hospital. PARTICIPANTS: A total of 32 glaucoma patients and 19 healthy controls. METHODS: All participants underwent positron emission tomography with (18)F-fluorodeoxyglucose, diffusion-tensor magnetic resonance imaging, and the 30-2 program of the Humphrey Visual Field Analyzer. MAIN OUTCOME MEASURES: Fractional anisotropy values of the optic radiation were compared between the two groups by defining regions of interests. Cerebral glucose metabolism was compared using statistical parametric mapping software. The correlation coefficients were calculated between the average of the total deviation of hemivisual fields of both eyes, fractional anisotropy values of the contralateral optic radiation and glucose metabolism in the contralateral striate cortex. RESULTS: Fractional anisotropy values in the bilateral optic radiations were significantly lower in patients with glaucoma. A significant glucose hypometabolism in the bilateral striate cortex was also observed in the glaucoma group. Regression analyses for glaucoma patients demonstrated that the average of the total deviation of hemivisual fields significantly correlated with both fractional anisotropy value of the contralateral optic radiation and glucose metabolism in the contralateral striate cortex. Moreover, there were significant correlations between fractional anisotropy values of the optic radiation and ipsilateral striatal glucose metabolism. CONCLUSION: We observed structural alterations in the bilateral optic radiations and glucose hypometabolism in the bilateral striate cortex of glaucoma patients.

Positive correlation between the degree of visual field defect and optic radiation damage in glaucoma patients.

PURPOSE: We evaluated optic radiation (OR) damage in patients with glaucoma by using fractional anisotropy (FA) of diffusion-tensor magnetic resonance imaging. METHODS: We studied 29 patients with glaucoma and 19 healthy controls. Regions of interest were placed over the bilateral anterior and posterior ORs on the FA maps, and the FA value of each region was measured. RESULTS: FA values of the bilateral anterior and posterior ORs were significantly lower in patients with glaucoma (anterior right, P = 0.0002; anterior left, P = 0.00028; posterior right, P = 0.0004; and posterior left, P = 0.0001) than in the healthy controls. In glaucoma patients, significant correlations were observed between the FA values and the average of the total deviation of the contralateral hemifields of both eyes (left hemifield and anterior right OR, correlation coefficient [r] = 0.46 [P = 0.013]; right hemifield and anterior left OR, r = 0.43 [P = 0.021]; left hemifield and posterior right OR, r = 0.54 [P = 0.0027]; and right hemifield and posterior left OR, r = 0.46 [P = 0.012]). CONCLUSIONS: FA values of the entire OR were decreased in glaucoma patients and correlated with the degree of visual field defect.

Increased adenosine A1 receptor levels in hemianopia patients after cerebral injury: an application of PET using 11C-8-dicyclopropylmethyl-1-methyl-3-propylxanthine.

PURPOSE: The aim of this study was to apply positron emission tomography (PET) with C-8-dicyclopropylmethyl-1-methyl-3-propylxanthine (MPDX), a radioligand for adenosine A1 receptor (A1R), to patients with hemianopia caused by brain injury to study neurorepair mechanisms in the brain. PATIENTS AND METHODS: Four patients with homonymous hemianopia and 15 healthy subjects were examined using PET to measure cerebral glucose metabolism, C-flumazenil (FMZ) binding to the central benzodiazepine receptor, and MPDX binding to A1R. Left and right regions of interest (ROIs) were selected, and semiquantitative data on the 3 kinds of PET examinations were obtained. The ROIs were referenced using the data for homologous regions in the contralateral hemisphere [ipsilateral/contralateral (I/C) ratio]. RESULTS: The I/C ratios for cerebral glucose metabolism and FMZ binding were low in the primary visual cortex (PVC) and visual association cortex in all the patients, whereas MPDX binding increased in the PVC in patients 1 and 2. Patients 1 and 2 experienced improvement in their visual field after 1 year. However, the other 2 patients showed no changes. We observed an increase in MPDX binding to A1R in the injured portion of the PVC in the patients who recovered. CONCLUSIONS: Evaluation of A1R by MPDX-PET may be useful for predicting prognosis and understanding the compensatory and reorganization processes in hemianopia caused by organic brain damage.

Analysis of gene expression in a human-derived glial cell line exposed to 2.45 GHz continuous radiofrequency electromagnetic fields.

The increasing use of mobile phones has aroused public concern regarding the potential health risks of radiofrequency (RF) fields. We investigated the effects of exposure to RF fields (2.45 GHz, continuous wave) at specific absorption rate (SAR) of 1, 5, and 10 W/kg for 1, 4, and 24 h on gene expression in a normal human glial cell line, SVGp12, using DNA microarray. Microarray analysis revealed 23 assigned gene spots and 5 non-assigned gene spots as prospective altered gene spots. Twenty-two genes out of the 23 assigned gene spots were further analyzed by reverse transcription-polymerase chain reaction to validate the results of microarray, and no significant alterations in gene expression were observed. Under the experimental conditions used in this study, we found no evidence that exposure to RF fields affected gene expression in SVGp12 cells.

Development of PET radiopharmaceuticals and their clinical applications at the Positron Medical Center.

The Positron Medical Center has developed a large number of radiopharmaceuticals and 36 radiopharmaceuticals have been approved for clinical use for studying aging and geriatric diseases, especially brain functions. Positron emission tomography (PET) has been used to provide a highly advanced PET-based diagnosis. The current status of the development of radiopharmaceuticals, and representative clinical and methodological results are reviewed.

Functional and neuroreceptor imaging of the brain in bicuculline-induced dystonic rats.

Dystonia is an involuntary movement disorder dominated by sustained muscle contractions that frequently cause twisting, repetitive movements, and postural changes. The purpose of this study was to determine the mechanism causing dystonia. We therefore employed a rat model of dystonia, which was induced by injecting (-)-bicuculine methiodide (BM), a gamma-aminobutyric acid A (GABA(A)) receptor antagonist, stereotaxically into the ventrolateral thalamic nuclei. Cerebral glucose metabolism reflecting cerebral activities and densities of central benzodiazepine and adenosine A(1) receptors that play an inhibitory role in neural excitation were evaluated in the brain by ex vivo autoradiography using appropriate (14)C/(18)F- or (11)C-labeled tracers. The dystonic signs were accompanied by increased glucose metabolism in the thalamus, substantia nigra, globus pallidus, and striatum. However, central benzodiazepine receptor density was not altered, and adenosine A(1) receptor density was reduced in the hippocampus. These results indicate the activation of a basal ganglia-thalamo-cortical motor circuit, which consists of the thalamus, substantia nigra, globus pallidus, and striatum. In this context, the activation of the above circuit has been reported in human dystonia patients. The decreased adenosine A(1) receptor density in the hippocampus might be related to a transient hippocampal dysfunction due to an acute type of dystonia. In conclusion, we have succeeded in generating a rat model of dystonia, and observed the activation of the basal ganglia-thalamo-cortical motor circuit that is related to dystonia.

Effects of 2.45 GHz electromagnetic fields with a wide range of SARs on bacterial and HPRT gene mutations.

Present day use of mobile phones is ubiquitous. This causes some concern for human health due to exposure to high-frequency electromagnetic fields (HFEMF) from mobile phones. Consequently, we have examined the effects of 2.45 GHz electromagnetic fields on bacterial mutations and the hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene mutations. Using the Ames test, bacteria were exposed to HFEMF for 30 min at specific absorption rates (SARs) from 5 to 200 W/kg. In all strains, there was no significant difference in the frequency of revertant colonies between sham exposure and HFEMF-exposed groups. In examination of mutations of the HPRT gene, Chinese hamster ovary (CHO)-K1 cells were exposed to HFEMF for 2 h at SARs from 5 to 200 W/kg. We detected a combination effect of simultaneous exposure to HFEMF and bleomycin at the respective SARs. A statistically significant difference was observed between the cells exposed to HFEMF at the SAR of 200 W/kg. Cells treated with the combination of HFEMF at SARs from 50 to 200 W/kg and bleomycin exhibited increased HPRT mutations. As the exposure to HFEMF induced an increase in temperature, these increases of mutation frequency may be a result of activation of bleomycin by heat. We consider that the increase of mutation frequency may be due to a thermal effect.

Effect of high-frequency electromagnetic fields with a wide range of SARs on chromosomal aberrations in murine m5S cells.

To investigate the induction of chromosomal aberrations in mouse m5S cells after exposure to high-frequency electromagnetic fields (HFEMFs) at 2.45 GHz, cells were exposed for 2 h at average specific absorption rates (SARs) of 5, 10, 20, 50 and 100 W/kg with continuous wave-form (CW), or at a mean SAR of 100 W/kg (with a maximum of 900 W/kg) with pulse wave-form (PW). The effects of HFEMF exposure were compared with those in sham-exposed controls and with mitomycin C (MMC) or X-ray treatment as positive controls. We examined all structural, chromatid-type and chromosome-type changes after HFEMF exposures and treatments with MMC and X-rays. No significant differences were observed following exposure to HFEMFs at SARs from 5 to 100 W/kg CW and at a mean SAR of 100 W/kg PW (a maximum SAR of 900 W/kg) compared with sham-exposed controls, whereas treatments with MMC and X-rays increased the frequency of chromatid-type and chromosome-type aberrations. In summary, HFEMF exposures at 2.45 GHz for 2 h with up to 100 W/kg SAR CW and an average 100 W/kg PW (a maximum SAR of 900 W/kg) do not induce chromosomal aberrations in m5S cells. Furthermore, there was no difference between exposures to CW and PW HFEMFs.

Effects of 2450 MHz electromagnetic fields with a wide range of SARs on methylcholanthrene-induced transformation in C3H10T1/2 cells.

This study examined whether 2450 MHz continuous wave high frequency electromagnetic fields (HFEMF) could induce cancer-like changes in mouse C3H10T1/2 cells, and whether HFEMF could initiate malignant or synergistic transformation. Transformed foci, Type II and Type III, were independently counted as the experiment endpoint. The cells were exposed to HFEMF alone at a wide range of specific absorption rates (SARs) of 5 to 200 W/kg for 2 h and/or were treated with a known initiating chemical, methylcholanthrene (MC) (2.5 microg/ml). No significant differences were observed in the malignant transformation (Type II + Type III) frequency between the controls and HFEMF with or without 12-O-tetradecanoylphorbol-13-acetate (TPA) (0.5 ng/ml), a tumor promoter that could enhance transformation frequency initiated by MC in multistage carcinogenesis. However, the transformation frequency for HFEMF at SAR of more than 100 W/kg with MC or MC plus TPA was increased compared with MC alone or MC plus TPA. On the other hand, the corresponding heat groups (heat alone, heat + MC, and heat + MC + TPA) did not increase transformation compared with each control level in C3H10T1/2 cells. This result suggests that 2450 MHz HFEMF could not contribute to the initiation stage of tumor formation, but it may contribute to the promotion stage at the extremely high SAR (100 W/kg).

A case of multiple sclerosis with homonymous hemianopia examined by positron emission tomography.

BACKGROUND: To demonstrate the efficacy of positron emission tomography (PET) for examining multiple sclerosis (MS) patients with hemianopia. CASE: A 20-year-old man visited us with a complaint of left homonymous hemianopia and headache. OBSERVATIONS: The patient's visual acuity was 1.2 (n.c.) OD and 0.9 (1.0) OS. Magnetic resonance imaging (MRI) showed a mass in the temporoparietal lobe. A pathological diagnosis of MS was made by brain biopsy. Low glucose metabolism in the lesion and visual cortex was observed by PET with (18)F-fluorodeoxy glucose. PET with (11)C-flumazenyl revealed a reduction of (11)C-uptake in the demyelinated optic radiation, and only a slight reduction of (11)C-uptake in the primary visual cortex. The results of (11)C-flumazenyl PET suggested a slight reduction of neuronal density. In 2 years, the visual field recovered to the normal state. CONCLUSION: PET can be a useful tool for estimating the visual outcome of patients with hemianopia in MS.

Neuroimaging analysis of a case with left homonymous hemianopia and left hemispatial neglect.

PURPOSE: To correlate the neuro-ophthalmological observations with the magnetic resonance images (MRI) and positron emission tomographic (PET) findings in a case with left homonymous hemianopia and left hemispatial neglect. CASE: A 57-year-old woman underwent surgery for a ruptured anterior communicating artery aneurysm. After she recovered consciousness, it was found that she had left homonymous hemianopia and left hemispatial neglect. Although the hemispatial neglect slowly improved, the homonymous hemianopia persisted. MRI and measurements of cerebral glucose metabolism by 2-fluoro-2-deoxy-D-glucose(FDG)-PET were performed 1 year later. RESULTS: MRI revealed infarctions on the medial surface of the frontal lobe, on the right medial surface of the occipital lobe, and global atrophy of the right cortical hemisphere. FDG-PET disclosed severe glucose hypometabolism in the entire right hemisphere. Glucose metabolism in the right occipital cortex was 61.1% of that in the homologous region on the left side, 62.8% in the right anterior cingulate gyrus, and 93.8% in the temporal-parietal-occipital junction. CONCLUSIONS: The low glucose metabolism in the right visual cortex explains the persistent left hemianopia, and that in the right anterior cingulate gyrus and the right temporal-parietal-occipital junction may be responsible for the left hemispatial neglect. The relatively mild damage in the right temporal-parietal-occipital junction explained the recovery of the neglect symptom. Measurements of regional cerebral glucose metabolism by PET are useful for determining the cause of cerebral visual dysfunction and its prognosis after a cerebral lesion.