Päivi Heikkinen

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.

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.

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.

Micronucleus frequency in erythrocytes of mice after long-term exposure to radiofrequency radiation

Purpose: The aim of the study was to investigate genotoxicity of long-term exposure to radiofrequency (RF) electromagnetic fields by measuring micronuclei in erythrocytes. The blood samples were collected in two animal studies evaluating possible cocarcinogenic effects of RF fields. Methods: In study A, female CBA/S mice were exposed for 78 weeks (1.5 h/d, 5 d/week) to either a continuous 902.5 MHz signal similar to that emitted by analog NMT (Nordic Mobile Telephone) phones at a whole-body specific absorption rate (SAR) of 1.5 W/kg, or to a pulsed 902.4 MHz signal similar to that of digital GSM (Global System for Mobile Communications) phones at 0.35 W/kg. A third group was sham-exposed, and a fourth group served as cage controls. All but the cage control animals were exposed to 4 Gy of x-rays during three first weeks of the experiment. In study B, female transgenic mice (line K2) and their nontransgenic littermates were exposed for 52 weeks (1.5 h/d, 5 d/week). Two digital mobile phone signals, GSM and DAMPS (Digital Advanced Mobile Phone System), were used at 0.5 W/kg. All but the cage-control animals were exposed 3 times per week to an ultraviolet radiation dose of 1.2 MED (minimum erythema dose). Results and conclusions: The results did not show any effects of RF fields on micronucleus frequency in polychromatic or normochromatic erythrocytes. The results were consistent in two mouse strains (and in a transgenic variant of the second strain), after 52 or 78 weeks of exposure, at three SAR levels relevant to human exposure from mobile phones, and for three different mobile signals.

Experimental studies on carcinogenicity of radiofrequency radiation in animals

In this paper, the authors present a comprehensive review of animal studies on carcinogenicity of radiofrequency (RF) electromagnetic fields. The rapid increase in mobile telephony has resulted in concerns regarding possible heath effects from the low-level but increasingly ubiquitous exposure to RF fields. The possible carcinogenicity of RF fields has been investigated in a number of experimental models including classical rodent bioassays, studies using genetically predisposed animals, cocarcinogenicity studies, and studies evaluating effects on the development of tumors from transplanted tumor cells. Overall, the results of these studies are rather consistent and indicate no carcinogenic effects at exposure levels relevant to human exposure from mobile phones. This finding is consistent with the results of the majority of epidemiological studies on mobile phone users, and suggests that RF field exposure below the present guidelines is not likely to cause cancer.

Chronic Exposure to 50-HZ Magnetic fields or 900-MHz Electromagnetic fields Does not alter Nocturnal 6-Hydroxymelatonin Sulfate Secretion in CBNS Mice

Several studies have reported that electromagnetic fields suppress nocturnal melatonin production in animals. In this study we investigated whether chronic (over 17 months) exposure to vertical 50-Hz magnetic fields with regularly varying intensity (1.3,13, and 130μT; 24 h/day) affects nocturnal 6-hydroxymelatonin sulfate (6-OHMS) production in female CBNS mice. The effects of 900 MHz radiofrequency radiation (90 midday) were also studied, using either continuous radiation with a specific absorption rate (SAR) of 1.5 W/kg or pulsed radiation with a pulse repetition rate of 217 MHz and a SAR (average) of 0.35 W/kg. Twenty-four mice per group were kept in metabolic cages (three animals per cage) for two nights (from 7 PM to 7 AM) with a 1-week intewal, and urine was collected. Urinary concentration of 6-OHMS, the main metabolite of melatonin, was determined by radio-immunoassay. Neither the extremely low-frequency magnetic field nor the radiofrequency radiation affected excretion of 6–OHMS in nocturnal urine.

Toxicological Profile of Ultrapure 2,2′,3,4,4′,5,5′-Heptachlorbiphenyl (PCB 180) in Adult Rats

PCB 180 is a persistent non-dioxin-like polychlorinated biphenyl (NDL-PCB) abundantly present in food and the environment. Risk characterization of NDL-PCBs is confounded by the presence of highly potent dioxin-like impurities. We used ultrapure PCB 180 to characterize its toxicity profile in a 28-day repeat dose toxicity study in young adult rats extended to cover endocrine and behavioral effects. Using a loading dose/maintenance dose regimen, groups of 5 males and 5 females were given total doses of 0, 3, 10, 30, 100, 300, 1000 or 1700 mg PCB 180/kg body weight by gavage. Dose-responses were analyzed using benchmark dose modeling based on dose and adipose tissue PCB concentrations. Body weight gain was retarded at 1700 mg/kg during loading dosing, but recovered thereafter. The most sensitive endpoint of toxicity that was used for risk characterization was altered open field behavior in females; i.e. increased activity and distance moved in the inner zone of an open field suggesting altered emotional responses to unfamiliar environment and impaired behavioral inhibition. Other dose-dependent changes included decreased serum thyroid hormones with associated histopathological changes, altered tissue retinoid levels, decreased hematocrit and hemoglobin, decreased follicle stimulating hormone and luteinizing hormone levels in males and increased expression of DNA damage markers in liver of females. Dose-dependent hypertrophy of zona fasciculata cells was observed in adrenals suggesting activation of cortex. There were gender differences in sensitivity and toxicity profiles were partly different in males and females. PCB 180 adipose tissue concentrations were clearly above the general human population levels, but close to the levels in highly exposed populations. The results demonstrate a distinct toxicological profile of PCB 180 with lack of dioxin-like properties required for assignment of WHO toxic equivalency factor. However, PCB 180 shares several toxicological targets with dioxin-like compounds emphasizing the potential for interactions.

Dopamine-dependent behavior in adult rats after perinatal exposure to purity-controlled polychlorinated biphenyl congeners (PCB52 and PCB180)

Since knowledge about toxic effects of non-dioxinlike (NDL) PCBs is fragmentary, regulatory panels have concluded that risk assessment of these congeners is hampered or impossible. As the dopaminergic system is one of the main targets in PCB-related neurotoxic effects after developmental exposure, we selected catalepsy induced by the dopamine receptor blocker haloperidol to characterize effects of the NDL congeners PCB52 and PCB180 in adult offspring from exposed rat dams. Rat dams were treated with PCB congeners by gavage using six dose levels (total doses: PCB52-0, 30, 100, 300, 1000 or 3000mg/kg body wt.; PCB180 - 0, 10, 30, 100, 300, or 1000mg/kg body wt.) to allow benchmark dose analysis of the results. Testing of adult offspring (starting at 180 days of age) for catalepsy induced by injection with haloperidol revealed slightly prolonged latencies to movement onset in female offspring exposed to PCB52. Exposure to PCB180 resulted in more pronounced effects, with generally reduced latencies in male offspring. These results indicate reduced dopaminergic activity after PCB52 exposure, whereas the outcome for PCB180 may be related to increased extracellular dopamine as reported in the literature. Benchmark dose analyses revealed that both PCB congeners exerted effects mainly at moderate exposure levels. Together, these results underline the importance of effects on the dopaminergic system as indicated by studies in human females after occupational PCB exposure.

Auditory effects of developmental exposure to purity-controlled Polychlorinated Biphenyls (PCB52 and PCB180) in rats

Polychlorinated biphenyls (PCBs) are still present in the environment, with ongoing exposure in humans, including babies nursed by their mothers. Whereas toxicity of dioxin-like PCBs is well described, less systematic knowledge is available for non-dioxin like PCBs (NDL-PCBs) that do not act via the Ah receptor. This study compared effects of developmental exposure to two ultrapure NDL-PCB congeners (PCB52 and PCB180) on auditory function in rats, using the brainstem auditory evoked potential (BAEP). Pregnant rats received repeated oral doses of PCB52 (total dose-0, 30, 100, 300, 1000, or 3000 mg/kg body weight) or of PCB180 (total dose-0, 10, 30, 100, 300, or 1000 mg/kg). BAEPs were recorded in adult male and female offspring after stimulation with clicks or pure tones in the frequency range from 0.5 to 16 kHz. Significant elevation of BAEP thresholds was detected in the low-frequency range after developmental exposure to PCB52. Calculation of benchmark doses revealed lowest values in the frequency range of 0.5-2 kHz. Effects were more pronounced in male compared with female offspring. Latencies of waves II and IV were prolonged in exposed males, whereas only wave IV was affected in females. PCB180 increased thresholds only at few conditions and only in female offspring. These results confirm that developmental exposure to ultrapure NDL-PCBs affects auditory function, but different congeners exhibit differences in potencies.