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Life-span exposure to sinusoidal-50 Hz magnetic field and acute low-dose γ radiation induce carcinogenic effects in Sprague-Dawley rats
Soffritti M, Tibaldi E, Padovani M, Hoel DG, Giuliani L, Bua L, Lauriola M, Falcioni L, Manservigi M, Manservisi F, Panzacchi S, Belpoggi F. Life-span exposure to sinusoidal-50 Hz magnetic field and acute low-dose γ radiation induce carcinogenic effects in Sprague-Dawley rats. Int J Radiat Biol. 2016 Feb 19:1-13. [Epub ahead of print].Abstract
Background In 2002 the International Agency for Research on Cancer classified extremely low frequency magnetic fields (ELFMF) as a possible carcinogen on the basis of epidemiological evidence. Experimental bioassays on rats and mice performed up to now on ELFMF alone or in association with known carcinogens have failed to provide conclusive confirmation.
Objectives To study the carcinogenic effects of combined exposure to sinusoidal-50 Hz (S-50Hz) magnetic fields and acute γ radiation in Sprague-Dawley rats.
Methods We studied groups of male and female Sprague-Dawley rats exposed from prenatal life until natural death to 20 or 1000 μT S-50Hz MF and also to 0.1 Gy γ radiation delivered as a single acute exposure at 6 weeks of age.
Results The results of the study showed significant carcinogenic effects for the mammary gland in males and females and a significant increased incidence of malignant schwannomas of the heart as well as increased incidence of lymphomas/leukemias in males.
Conclusions These results call for a re-evaluation of the safety of non-ionizing radiation.
From 1979 until now the results of numerous epidemiological research projects carried out on children living in houses near electricity power lines as well as on occupationally-exposed workers have suggested that there is a potential carcinogenic risk from electricity-generated magnetic fields. An initial association between exposure and leukemia in children was proposed in 1979 (Wertheimer and Leeper 1979). Subsequently Milham (1982) reported a correlation between leukemia and extremely low-frequency magnetic fields (ELFMF) in adults. An increased relative risk of breast cancer was observed in women, particularly in those under 55 years of age (Wertheimer and Leeper 1979). An excess of male breast cancers associated with ELFMF exposure was reported later (Matanoski and Breysse 1989; Matanoski et al. 1991; Demers et al. 1991; Tynes et al. 1992). In 2000, a pooled analysis identified a significant increased risk of childhood leukemia at exposures in excess of 0.4 μT (Ahlbom et al.2000). The epidemiological evidence led the International Agency for Research on Cancer to classify ELFMF as a possible carcinogen (World Health Organization [WHO]-IARC 2002). Further case control studies (Draper et al. 2005; Kroll et al. 2010; Sermage-Faure et al. 2013) and a pooled analysis based on primary data (Kheifets et al. 2010) confirmed the reliability of an approximately two-fold increased risk of childhood leukemia at magnetic fields levels above 0.3–0.4 μT.
Indeed, despite the epidemiological evidence of an association, experimental studies in which ELFMF were administered alone have failed to provide conclusive confirmation. Experimentally, it has not been possible to identify a carcinogenic effect from magnetic fields and no accepted mechanism by which they might cause cancer has been described. Up to now, five long-term carcinogenicity bioassays on ELFMF administered alone, four conducted on rats (Margonato et al. 1995; Mandeville et al.1997; Yasui et al. 1997; Boorman et al. 1999b) and one on mice (McCormick et al. 1999) have failed to show convincing evidence of any carcinogenic effect. The results of the NTP study showed equivocal evidence for the carcinogenic activity of 60-Hz magnetic fields in Fischer 344 rats on the basis of the increased incidence of thyroid gland C-cell neoplasms in males exposed to 2 or 200 μT. There was no evidence of carcinogenicity in male rats exposed at 1000 μT or again in female or male mice (Boorman et al. 1999b).
In conclusion, studies to date have typically lacked the size to identify rare events and have not lasted long enough to track diseases in later life. Critically, they have also not taken into account in utero exposure, apart from the study conducted by Mandeville et al. (1997) on small groups of Fisher 344 rats in which exposure began from day 20 of gestation.
The experiments were planned as an integrated experimental project in which the exposure of the experimental animals to ELFMF started from prenatal life and lasted until natural death. The aim of the studies was to assess the qualitative-quantitative carcinogenic effects of sinusoidal-50 Hz MF (S-50Hz MF), trying to simulate possible human exposure situations. Moreover, large experimental groups were used in order to increase the statistical power and thus improve the evaluation of possible low-magnitude oncogenic effects. For this purpose the project includes studies to assess: (1) the qualitative-quantitative potential carcinogenic effects of S-50Hz MF alone with reference to intensity and continuity-discontinuity of electric current; (2) the carcinogenic effects of S-50Hz MF combined with acute exposure to ionizing radiation; (3) the carcinogenic effects of S-50Hz MF combined with exposure to carcinogenic chemical agents such as formaldehyde or aflatoxin B1; and (4) the possible pathogenic mechanisms at the basis of potential carcinogenic effects, as revealed by molecular profiling investigations.
The plan of the project, encompassed four experiments using 7133 rats in all. The four experiments started concurrently and the experimental animals were those born during the breeding of 2100 breeders.
Treatment with S-50Hz MF began during fetal life exposing the female breeders from the 12th day of pregnancy. The daily exposure to S-50Hz MF for both breeders and offspring was 19 h and for the offspring lasted until natural death. The animals of groups III and IV were also treated with an acute dose of 0.1 Gy of γ radiation at 6 weeks of age. The animals of group II were exposed only to γ radiation.
The results of the study show, for the first time, that exposure of Sprague-Dawley rats to S-50Hz MF from prenatal life until natural death plus acute low-dose γ radiation delivered at 6 weeks of age, compared to untreated controls, significantly enhances the incidence of several tumors in males and females, namely: (a) a significant dose-related increased incidence of mammary adenocarcinomas in males and females in particular in males exposed to 20 μT plus 0.1 Gy and in females exposed to 1000 μT plus 0.1 Gy; (b) in males a significant dose-related increased incidence of heart malignant schwannomas with a significant increase among males exposed to 20 μT plus 0.1 Gy (p ≤ 0.05) and to 1000 μT plus 0.1 Gy; and (c) a significant increased incidence of hematopoietic neoplasias in males treated at 1000 μT plus 0.1 Gy. Concerning our S-50Hz MF alone study arm, no effects were shown on these cancer endpoints.
When rats exposed to MF and 0.1 Gy are compared with the group exposed to 0.1 Gy alone, a significant increased incidence was observed in mammary adenocarcinomas among females exposed to 1000 μT plus 0.1 Gy, as well as in hematopoietic neoplasms among males exposed to 1000 μT plus 0.1 Gy.Conclusions
The results of this study have demonstrated for the first time that exposure to S-50Hz MF from prenatal life until natural death enhances the carcinogenic effects of γ radiations in male and female Sprague-Dawley rats.
The results of our study cannot be compared to those of the studies conducted in the past because of our different experimental design, large number of animals per group, starting exposure from prenatal life and duration of observation until natural death, our complete histopathological evaluation of all organs and tissues, as well as the possibility we had of comparing the incidence of various tumors in rats treated with 0.1 Gy and among negative controls as well as with concurrent males and females exposed to 1000 μT MF alone.
The type and level of 0.1 Gy exposure planned for this study cannot be considered unusual in the human working place or in general life. For instance, during computed tomography (CT) investigations, the organ being studied typically receives a radiation dose from 15 mGy (in adults) to 30 mGy (in children) with an average of 2–3 scans per study (which corresponds at least to 120 mGy, which is >0.1 Gy) (Brenner and Hall 2007). Radiation exposure from CT scans and increased cancer risk in adults (Sodickson et al. 2009) and in children (Pearce et al. 2012) has been reported. Moreover S-50Hz MF may enhance progression of a number of lesions from benign to malignant. Indeed, our results on mammary cancer as well as on leukemia and malignant schwannomas of the heart should call attention to situations in which exposure to MF may be associated with exposure to low doses of well-known carcinogenic agents such as ionizing radiation or other chemical carcinogens.
In conclusion, in our opinion these results call for a re-evaluation of the safety of non-ionizing radiation particularly at this time when the pressure to move from conventional fuels-based mobility to electric mobility deserves high priority in the EU and US and other industrialized countries.--
Joel M. Moskowitz, Ph.D., Director Center for Family and Community Health School of Public Health University of California, Berkeley Electromagnetic Radiation Safety