Hannele Huuskonen

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.

Teratogenic and reproductive effects of low-frequency magnetic fields

The public discussion of the health hazards of Ž . low-frequency LF; 0–100 kHz magnetic fields Ž . MF has focused on the possible association with cancer, and much less attention has been paid to evaluating their role in reproductive health. However, several studies on the effects of MFs on reproduction have been conducted during the last decade. These studies were initiated by a study reporting that MFs may interfere with chick embryo development w x 1 , small clusters of birth defects and miscarriages observed among operators of video display terminals, and an epidemiological study suggesting that maternal use of electrically heated waterbeds and w x electric blankets may affect fetal development 2 . The teratogenic effects of chemical and physical environmental agents are often related to their ability to damage DNA. The possibility that MFs induce genotoxic effects is discussed elsewhere in this issue. This paper reviews studies on the possible effects of

Increased resorptions in CBA mice exposed to low‐frequency magnetic fields: An attempt to replicate earlier observations

This paper has two aims. First, it reports the findings of a study on the effects of low-frequency magnetic fields on reproduction. Second, it serves as an example of an attempt to replicate the results of an experimental study in an independent laboratory and discusses some of the problems of replication studies. To try to replicate the findings of a study reporting increased resorptions (fetal loss) in mice exposed to 20 kHz magnetic fields with sawtooth waveform and to study the possible effects of 50 Hz sinusoidal fields, pregnant mice were exposed to magnetic fields from day 0 to 18 of pregnancy, 24 h per day. The flux densities of the vertical magnetic fields were 15 microT (peak-to-peak) at 20 kHz and 13 or 130 microT (root mean square) at 50 Hz. Two strains of animals were used: CBA/S mice imported from the laboratory reporting the original observations, and a closely related strain CBA/Ca. The CBA/S mice were cleaned of pathogenic microbes and parasites before they were imported into our laboratory. The magnetic field exposures did not affect resorption rate in CBA/Ca mice. In CBA/S, the frequency of resorptions was higher in the exposed mice than in the control group. However, the increase was not significantly different from either the no-effect hypothesis or the results of the original study we were attempting to replicate. Differences between the two studies and difficulties in interpreting the results are discussed. It is concluded that the results tend more to support than argue against increased resorptions in CBA/S mice exposed to the 20 kHz magnetic field. The results demonstrate that animal strain is an important variable in bioelectromagnetics research: even closely related strains may show different responses to magnetic field exposure.

EFFECTS OF LOW-FREQUENCY MAGNETIC FIELDS ON FETAL DEVELOPMENT IN CBA/CA MICE

Effects of alternating magnetic fields (MFs) on the embryonic and fetal development in CBA/Ca mice were studied. Mated females were exposed continuously to a sinusoidal 50 Hz (13 microT or 0.13 mT root mean square) or a sawtooth 20 kHz (15 microT peak-to-peak) MF from day 0 to day 18 of pregnancy for 24 h/day until necropsied on day 18. Control animals were kept under the same conditions without the MF. MFs did not cause maternal toxicity. No adverse effects were seen in maternal hematology and the frequency of micronuclei in maternal bone marrow erythrocytes did not change. The MFs did not increase the number of resorptions or fetuses with major or minor malformations in any exposure group. The mean number of implantations and living fetuses per litter were similar in all groups. The corrected weight gain (weight gain without uterine content) of dams, pregnancy rates, incidences of resorptions and late fetal deaths, and fetal body weights were similar in all groups. There was, however, a statistically significant increase in the incidence of fetuses with at least three skeletal variations in all groups exposed to MFs. In conclusion, the 50 Hz or 20 kHz MFs did not increase incidences of malformations or resorptions in CBA/Ca mice, but increased skeletal variations consistently in all exposure groups.

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.

Effects of low-frequency magnetic fields on implantation in rats☆

Effects of 50-Hz sinusoidal magnetic fields (MFs) on embryo implantation, serum 17beta-estradiol, progesterone, testosterone, and melatonin levels, and on estrogen receptor (ER) and progesterone receptor (PgR) densities in the uterus were studied during the preimplantation and implantation periods in rats. Pregnant Wistar rats were exposed to magnetic r.m.s. field strengths of 10 or 100 A/m (13 or 130 microT) or sham-exposed (controls) from day 0 of pregnancy for 24 h/day and killed during light and dark periods between 70 h and 176 h after ovulation. MFs did not influence the mean total number of implantations. The nocturnal mean serum melatonin concentration decreased by 34 and 38% at 10 and 100 A/m, respectively. At the same time, the first embryos, at an early developmental stage, arrived in the uterus in the MF-exposed groups. Serum estradiol and progesterone levels did not significantly change. Nuclear PgR and ER densities in the uterus decreased before implantation and there was an increased incidence of early stage embryos and fewer hatched embryos were found in the uterus at 100 A/m. During the early implantation period, the uterine cytosolic ER/PgR-ratio was increased at 100 A/m and no implants were concomitantly found in uterus. The nuclear ER/PgR-ratio decreased during implantation in both MF-groups due to decreased nuclear ER density. At the same time, 19% and 15% of the embryos (calculated from the corpora luteae) at 10 and 100 A/m, respectively, were yet morulae and not implanted. In summary, the results show that MFs do not impair implantation in rats although there may be some borderline changes in the transport and development of embryos and associated endocrinologic parameters.

Effects of gestational exposure to a video display terminal-like magnetic field (20-kHz) on CBA/S mice

Possible adverse effects of magnetic fields (MFs) on reproduction have been an open question. To verify the embryo-lethal effect of pulsed MF of the type emitted by video display terminals (VDTs) reported previously in CBA/S mice, a developmental toxicity study was conducted in animals of the same origin. Mated CBA/S mice (80-86 pregnant animals per group) were exposed to a 20-kHz MF with sawtooth waveform continuously from gestational day 0-18. The flux density of the vertical MF was 15 microT peak-to-peak (150 mG). This field was previously reported to increase the number of resorptions in CBA/S mice. On gestational day 18, the dams were killed and blood and bone marrow samples were taken for hematology and micronuclei analysis, respectively. The number of corpora lutea was counted and the content of the uterus examined. There were no statistically significant differences in maternal or fetal body weights, number of corpora lutea, implantations, resorptions, dead and live fetuses, or external and skeletal malformations. MF did not alter the number of blood cells or cause micronuclei in bone marrow erythrocytes in the dams. The mean number of resorptions was slightly but not statistically significantly, higher in the MF group than in controls. The results do not indicate marked developmental, hematological, or clastogenic effects of 20-kHz MFs.

The developmental toxicity of 2-ethylhexanoic acid in Wistar rats

Abstract The developmental toxicity of 2-ethylhexanoic acid (2-EHA), a wood preservative and a mammalian metabolite of di-(2-ethylhexyl) phthalate was examined in Wistar rats (20–21 pregnant females/dose). Mated animals were exposed to 2-EHA in their drinking water at doses of 100, 300, or 600 mg/kg/day on Days 6–19 of gestation. Control animals received vehicle water. The fetuses were examined (on Gestational Day 20) for external, visceral, and skeletal malformations and variations. 2-EHA was marginally toxic to the dams at 600 mg/kg, but not at lower doses, since the mean near term body weight was reduced by 11%. This dose level was also slightly fetotoxic as indicated by a 5 to 8% decrease in the mean fetal body weight both in males and females. No treatment-related effects were observed in the number of implantations or live fetuses. At doses of 100 mg/kg and above, 2-EHA caused skeletal malformations (clubfoot, absence of fibula, polydactyly), while the development of visceral tissues was less affected. The number of affected fetuses increased in a dose-dependent way (4.9, 8.9, and 15.3% of treated offspring at 100, 300, and 600 mg/kg/day, respectively, vs 2.4% control). These results indicate that 2-EHA is teratogenic in rats already at doses which are not yet maternally toxic. The skeleton appears to be the main target of 2-EHA in developing rats.

Toxic effects and excretion in urine of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX) in the rat after a single oral dose

Toxic effects and excretion in urine of 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), the potent mutagenic compound in chlorinated drinking water, was evaluated in male Wistar rats by the up-and-down method. MX was dosed by gavage in deionized water at doses between 200 mg/kg and 600 mg/kg, for one animal at a time, and effects were observed for 14 days. Urine was collected in metabolism cages up to 72 h after dosing for chemical analysis of MX in urine. The animals receiving 200 mg/kg did not display clear clinical signs but at higher doses the signs of ill effects included dyspnea, laborious, wheezing and gasping breathing, decreased spontaneous motor activity, ataxia, nostril discharges, catalepsia and cyanosis. In necropsy bronchi contained foamy liquid and the lungs appeared edematous and spongy. The stomach cavity was expanded due to accumulation of fluid and gas and the gastrointestinal tract from stomach to caecum was reddish. Microscopically, the main target organ of toxicity was the gastrointestinal tract (diffuse congestion and necrosis in the mucosa). Signs of toxicity were recorded also in lungs (slight edema) and kidneys (dilated tubules, thin tubular epithelium, brownish tubular and interstitial concretion). The LD50 in 48 h was 230 mg/kg. Only 0.03–0.07% of the dose (200 mg/kg or 300 mg/kg) was excreted in urine as intact MX. The results indicate that at high doses MX has a strong local irritating effect in the gastrointestinal tract and it probably increases liquid permeability in lungs. MX may also cause tubular damage in kidneys. Data also indicate that after an oral dose only traces of MX are excreted in urine as intact compound, suggesting that MX is subjected to intense metabolism before excretion, even at lethal doses.