Timo Kumlin

Mobile Phone Radiation and the Developing Brain: Behavioral and Morphological Effects in Juvenile Rats

Abstract Kumlin, T., Iivonen, H., Miettinen, P., Juvonen, A., van Groen, T., Puranen, L., Pitkäaho, R., Juutilainen, J. and Tanila, H. Mobile Phone Radiation and the Developing Brain: Behavioral and Morphological Effects in Juvenile Rats. Radiat. Res. 168, 471–479 (2007). The increasing use of mobile phones by children and teenagers has raised concerns about their safety. Addressing such concerns is difficult, because no data are available on possible effects from long-term exposure to radiofrequency (RF) fields during the development of the nervous system. Possible morphological and functional changes were evaluated in the central nervous system of young male Wistar rats exposed to 900 MHz mobile phone signal for 2 h/day on 5 days/week. After 5 weeks of exposure at whole-body average specific energy absorption rates of 0.3 or 3.0 W/kg or sham exposure, six rats per group were examined histologically, and the remaining 18 rats per group were subjected to behavioral tests. No degenerative changes, dying neurons, or effects on the leakage of the blood-brain barrier were detected. No group differences were observed in the open-field test, plus maze test or acoustic startle response tests. In the water maze test, however, significantly improved learning (P = 0.012) and memory (P = 0.01) were detected in rats exposed to RF fields. The results do not indicate a serious threat to the developing brain from mobile phone radiation at intensities relevant to human exposure. However, the interesting finding of improved learning and memory warrants further studies.

Do extremely low frequency magnetic fields enhance the effects of environmental carcinogens? A meta-analysis of experimental studies.

Purpose: This paper is a meta-analysis of data from in vitro studies and short-term animal studies that have combined extremely low frequency magnetic fields with known carcinogens or other toxic physical or chemical agents. Materials and methods: The data was analyzed by systematic comparison of study characteristics between positive and negative studies to reveal possible consistent patterns. Results: The majority of the studies reviewed were positive, suggesting that magnetic fields do interact with other chemical and physical exposures. Publication bias is unlikely to explain the findings. Interestingly, a nonlinear ‘dose-response’ was found, showing a minimum percentage of positive studies at fields between 1 and 3 mT. The radical pair mechanism (magnetic field effects on recombination of radical pairs) is a good candidate mechanism for explaining the biphasic dose-response seen in the present analysis. Conclusions: Most of the studies reviewed used magnetic fields of 100 μT or higher, so the findings are not directly relevant for explaining the epidemiological findings suggesting increased risk of childhood leukemia above 0.4 μT. However, confirmed adverse effects even at 100 μT would have implications for risk assessment and management, including the need to reconsider the exposure limits for magnetic fields. There is an obvious need for further studies on combined effects with magnetic fields.

Effects of mobile phone radiation on X-ray-induced tumorigenesis in mice.

Abstract Heikkinen, P., Kosma, V-M., Hongisto, T., Huuskonen, H., Hyysalo, P., Komulainen, H., Kumlin, T., Lahtinen, T., Lang, S., Puranen, L. and Juutilainen, J. Effects of Mobile Phone Radiation on X-Ray-Induced Tumorigenesis in Mice. Radiat. Res. 156, 775–785 (2001). The increased use of mobile phones has raised the question of possible health effects of such devices, particularly the risk of cancer. It seems unlikely that the low-level radiofrequency (RF) radiation emitted by them would damage DNA directly, but its ability to act as a tumor promoter is less well characterized. In the current study, we evaluated the effect of low-level RF radiation on the development of cancer initiated in mice by ionizing radiation. Two hundred female CBA/S mice were randomized into four equal groups at the age of 3 to 5 weeks. The mice in all groups except the cage-control group were exposed to ionizing radiation at the beginning of the study and then to RF radiation for 1.5 h per day, 5 days a week for 78 weeks. One group was exposed to continuous NMT (Nordic Mobile Telephones)-type frequency-modulated RF radiation at a frequency of 902.5 MHz and a nominal average specific absorption rate (SAR) of 1.5 W/kg. Another group was exposed to pulsed GSM (Global System for Mobile)-type RF radiation (carrier-wave frequency 902.4 MHz, pulse frequency 217 Hz) at a nominal average SAR of 0.35 W/kg. The control animals were sham-exposed. Body weight, clinical signs, and food and water consumption were recorded regularly. Hematological examinations and histopathological analyses of all lesions and major tissues were performed on all animals. The RF-radiation exposures did not increase the incidence of any neoplastic lesion significantly. We conclude that the results do not provide evidence for cancer promotion by RF radiation emitted by mobile phones.

Effects of mobile phone radiation on UV-induced skin tumourigenesis in ornithine decarboxylase transgenic and non-transgenic mice.

Purpose: The effects of low-level radiofrequency radiation (RFR) on ultraviolet (UV)-induced skin tumorigenesis were evaluated in ornithine decarboxylase (ODC) and non-transgenic mice. Materials and methods: Transgenic female mice over-expressing the human ODC gene and their non-transgenic littermates (20 animals in the cage control group, and 45-49 animals in the other groups) were exposed for 52 weeks to UV radiation or a combination of UV radiation and pulsed RFR. The UV dose was 240 Jm−2 (1.2 ×human minimum erythemal dose) delivered three times a week. One group of animals was exposed to Digital Advanced Mobile Phone System (DAMPS)-type RFR, the other group to Global System for Mobile (GSM)-type RFR at a nominal average specific absorption rate of 0.5 W kg−1, 1.5 h day−1, for 5 days a week. The skin was carefully palpated weekly for macroscopic tumours. Histopathological analyses of all skin lesions and of a specified dorsal skin area were performed on all animals. Results: UV exposure resulted in development of macroscopic skin tumours in 11.5 and 36.8% of non-transgenic and transgenic animals, respectively. The RFR exposures did not give a statistically significant effect on the development of skin tumours in either transgenic or non-transgenic animals, or in combined analysis, but tumour development appeared slightly accelerated especially in non-transgenic animals. No effects of RFR exposures were found on excretion of 6-hydroxymelatonin sulphate into urine or on polyamine levels in dorsal skin. Conclusion: RFR exposures did not significantly enhance skin tumourigenesis. However, the slightly accelerated tumour development may warrant further evaluation.

Review of possible modulation‐dependent biological effects of radiofrequency fields

The biological effects of modulated radiofrequency (RF) electromagnetic fields have been a subject of debate since early publications more than 30 years ago, suggesting that relatively weak amplitude-modulated RF electromagnetic fields have specific biological effects different from the well-known thermal effects of RF energy. This discussion has been recently activated by the increasing human exposure to RF fields from wireless communication systems. Modulation is used in all wireless communication systems to enable the signal to carry information. A previous review in 1998 indicated that experimental evidence for modulation-specific effects of RF energy is weak. This article reviews recent studies (published after 1998) on the biological effects of modulated RF fields. The focus is on studies that have compared the effects of modulated and unmodulated (continuous wave) RF fields, or compared the effects of different kinds of modulations; studies that used only one type of signal are not included. While the majority of recent studies have reported no modulation-specific effects, there are a few interesting exceptions indicating that there may be specific effects from amplitude-modulated RF fields on the human central nervous system. These findings warrant follow-up studies.

Nocturnal 6-hydroxymelatonin sulfate excretion in female workers exposed to magnetic fields

The objective of this study was to determine whether daytime occupational exposure to extremely low frequency magnetic fields (MFs) suppresses nocturnal melatonin production. Sixty female volunteers were recruited. Thirty‐nine worked in a garment factory, and 21 office workers served as a reference group. Exposure assessment was based on the type of sewing machine used and MF measurements around each type of machine. Eye‐level MF flux density was used to classify the operators to higher (>1 μT) and lower (0.3–1 μT) exposure categories. A third group of factory workers had diverse MF exposures from other sources. The reference group had average exposure of about 0.15 μT. Urine samples were collected on Friday and Monday for three consecutive weeks. Melatonin production was assessed as urinary 6‐hydroxymelatonin sulfate (6‐OHMS) excretion. The ratio of Friday morning/Monday morning 6‐OHMS was used to test the hypothesis that melatonin production is suppressed after 4 days of occupational MF exposure with significant recovery during the weekend. Possible chronic suppression of melatonin production was evaluated by studying exposure‐related differences in the Friday values by multivariate regression analysis. The Monday/Friday ratios were close to 1.0, suggesting that there is no increase in melatonin production over the weekend. The average 6‐OHMS excretion on Friday was lower among the factory workers than in the reference group, but no monotonous dose–response was observed. Multivariate regression analysis identified MF exposure, smoking, and age as significant explanatory variables associated with decreased 6‐OHMS excretion.

Investigation of Co-genotoxic Effects of Radiofrequency Electromagnetic Fields In Vivo

Abstract Verschaeve, L., Heikkinen, P., Verheyen, G., Van Gorp, U., Boonen, F., Vander Plaetse, F., Maes, A., Kumlin, T., Mäki-Paakkanen, J., Puranen, L. and Juutilainen, J. Investigation of Co-genotoxic Effects of Radiofrequency Electromagnetic Fields In Vivo. Radiat. Res. 165, 598–607 (2006). We investigated the possible combined genotoxic effects of radiofrequency (RF) electromagnetic fields (900 MHz, amplitude modulated at 217 Hz, mobile phone signal) with the drinking water mutagen and carcinogen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX). Female rats were exposed to RF fields for a period of 2 years for 2 h per day, 5 days per week at average whole-body specific absorption rates of 0.3 or 0.9 W/kg. MX was given in the drinking water at a concentration of 19 μg/ml. Blood samples were taken at 3, 6 and 24 months of exposure and brain and liver samples were taken at the end of the study (24 months). DNA damage was assessed in all samples using the alkaline comet assay, and micronuclei were determined in erythrocytes. We did not find significant genotoxic activity of MX in blood and liver cells. However, MX induced DNA damage in rat brain. Co-exposures to MX and RF radiation did not significantly increase the response of blood, liver and brain cells compared to MX exposure only. In conclusion, this 2-year animal study involving long-term exposures to RF radiation and MX did not provide any evidence for enhanced genotoxicity in rats exposed to RF radiation.

Effects of 50 Hz magnetic fields on UV-induced skin tumourigenesis in ODC-transgenic and non-transgenic mice

PURPOSE To study the possible role of 50 Hz magnetic fields (MF) in UV-induced skin tumourigenesis using a sensitive animal model. MATERIALS AND METHODS Transgenic mice (line K2) over-expressing the human ornithine decarboxylase (ODC) gene and their non-transgenic littermates were exposed for 10.5 months to UV-only or a combination of UV and a continuous (100 microT) or an intermittent MF with varying intensity (1.3-130 microT). RESULTS Both MF exposure and transgenicity enhanced the onset rate of macroscopically detectable tumours, but the effect was statistically significant only for the MF exposure (p < 0.015). The number of animals bearing malignant tumours was low and similar in all exposure groups. Epidermal cysts (EC) appeared to be strongly associated with both MF exposure and high ODC activity (transgenic animals). However, EC are not known to be associated with carcinogenesis. The UV-only or combined UV and MF exposure did not affect the ODC activities measured at the end of the exposure. CONCLUSIONS These results support the proposed tumour-promoting effect of MF, but do not suggest an important role for increased ODC activity in this process.

No Effects of Radiofrequency Radiation on 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone-Induced Tumorigenesis in Female Wistar Rats

Abstract Heikkinen, P., Ernst, H., Huuskonen, H., Komulainen, H., Kumlin, T., Mäki-Paakkanen, J., Puranen, L. and Juutilainen, J. No Effects of Radiofrequency Radiation on 3-Chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone-Induced Tumorigenesis in Female Wistar Rats. Radiat. Res. 166, 397–408 (2006). This study evaluated possible effects of radiofrequency (RF) radiation on tumorigenesis induced by the mutagen 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) given in drinking water. Female Wistar rats aged 7 weeks at the beginning of the experiments were randomly divided into four groups of 72 animals: a cage-control group and three MX-exposed groups (a daily average dose of 1.7 mg MX/kg body weight for 104 weeks), of which two were exposed to 900 MHz pulsed RF radiation and the third served as a sham-RF-radiation group. The RF-radiation groups were exposed 2 h per day, 5 days per week for 104 weeks at nominal whole-body average SARs of 0.3 W/kg and 0.9 W/kg. Complete histopathology was performed on the rats of the three MX-exposed groups. The tumor types and incidences observed in the MX-exposed animals were similar to those reported earlier in MX-exposed female Wistar rats. RF radiation did not statistically significantly affect mortality or organ-specific incidence of any tumor type. The only statistically significant difference was an increase in the combined frequency of vascular tumors of the mesenteric lymph nodes in the high-RF-radiation group compared to the sham-RF-radiation group. However, additional histopathological analysis of the cage-control animals suggested that this difference was due to unusually low frequency of this type of tumor in the sham-RF-radiation group rather than a high frequency in the high-RF-radiation group. With respect to non-neoplastic findings, statistically significant differences between the RF-radiation groups and the sham-RF-radiation group were observed only for single findings in the lacrimal glands, lungs, liver and skin. Such changes are commonly seen in aged rats and were considered to be unrelated to RF radiation. The results of the present study do not support co-carcinogenic effects of low-level long-term RF-radiation exposure in rats.

Chronic UVR Causes Increased Immunostaining of CD44 and Accumulation of Hyaluronan in Mouse Epidermis

Chronic intense UV radiation is the main cause of epidermal tumors. Because hyaluronan (HA), a large extracellular polysaccharide, is known to promote malignant growth, hyaluronan expression was studied in a model in which long-term UV radiation (UVR) induces epidermal tumors. Mouse back skin was exposed three times a week for 10.5 months to UVR corresponding to one minimal erythema dose, processed for histology, and stained for hyaluronan and the hyaluronan receptor CD44. This exposure protocol caused epidermal hyperplasia in most of the animals; tumors, mainly squamous cell carcinomas (SCCs), were found in ~20% of the animals. Specimens exposed to UVR showed increased hyaluronan and CD44 staining throughout the epidermal tissue. In hyperplastic areas, hyaluronan and CD44 stainings correlated positively with the degree of hyperplasia. Well-differentiated SCCs showed increased hyaluronan and CD44 staining intensities, whereas poorly differentiated tumors and dysplastic epidermis showed areas where HA and CD44 were locally reduced. The findings indicate that HA and CD44 increase in epidermal keratinocytes in the premalignant hyperplasia induced by UV irradiation and stay elevated in dysplasia and SCC, suggesting that the accumulation of hyaluronan and CD44 is an early marker for malignant transformation and may be a prerequisite for tumor formation.