Tumor promotion by exposure to radiofrequency electromagnetic fields below exposure limits for humans

Joel's comments: This is an important study on several accounts. First, the study demonstrates that the tumor-enhancing effects from exposure to UMTS (3G) cell phone radiation observed in a previous animal study are reproducible. Reproducibility is one of the foundations of the scientific method. 

Second, the study did not find a dose-response effect. Rather "many of the tumor-promoting effects in our study were seen at low to moderate exposure levels (0.04 and 0.4 W/kg SAR), thus well below exposure limits for the users of mobile phones." The tumor-promoting effects were not observed when the animals were exposed to 2.0 W/kg SAR, the legal limit in many countries outside the U.S. (where the limit is 1.6 W/kg.) The SAR exposure limits adopted by most countries assumes a dose-response relationship between the exposure and adverse health effects. The nonlinear effects observed in this study suggest that the SAR methodology is inadequate to protect human health.

Third, The authors explain why some researchers have had difficulty in reproducing the results of earlier studies -- their methods deviate in critical ways from the original experiments. Hence, these so-called "replication studies" fail to reproduce the effects observed in earlier studies.

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Tumor promotion by exposure to radiofrequency electromagnetic fields below exposure limits for humans

Alexander Lerchl, Melanie Klose, Karen Grote, Adalbert F.X. Wilhelm, Oliver Spathmann, Thomas Fiedler, Joachim Streckert ,Volkert Hansenc, Markus Clemens. Tumor promotion by exposure to radiofrequency electromagnetic fields below exposure limits for humans. Biochemical and Biophysical Research Communications. Available online 6 March 2015.

Abstract

The vast majority of in vitro and in vivo studies did not find cancerogenic effects of exposure to electromagnetic fields (RF-EMF), i.e.emitted by mobile phones and base stations. Previously published results from a pilot study with carcinogen-treated mice, however, suggested tumor-promoting effects of RF-EMF (Tillmann et al., 2010). 
We have performed a replication study using higher numbers of animals per group and including two additional exposure levels (0 (sham), 0.04, 0.4 and 2 W/kg SAR). 
We could confirm and extend the originally reported findings. Numbers of tumors of the lungs and livers in exposed animals were significantly higher than in sham-exposed controls. In addition, lymphomas were also found to be significantly elevated by exposure. 
A clear dose-response effect is absent. We hypothesize that these tumor-promoting effects may be caused by metabolic changes due to exposure. Since many of the tumor-promoting effects in our study were seen at low to moderate exposure levels (0.04 and 0.4 W/kg SAR), thus well below exposure limits for the users of mobile phones, further studies are warranted to investigate the underlying mechanisms. 
Our findings may help to understand the repeatedly reported increased incidences of brain tumors in heavy users of mobile phones.

Highlights

• Tumor-promoting effects of RF-EMF exposed mice have been reported in 2010.

• We have replicated the study with higher numbers of mice per group.

• We could fully confirm the previous results, thus the effects are reproducible.

• Apparently, no clear dose-response relationship is evident.

• We hypothesize that metabolic changes are responsible for the effects observed.

http://bit.ly/1EXI3Hq

Excerpts

In 2010, a study was published [4] showing tumor-promoting effects of life-long exposure to RF-EMF (Universal Mobile Telecommunication System, UMTS) at moderate exposure levels in mice treated with a carcinogen (ethylnitrosourea, ENU) in utero. Those results were potentially influenced by an unexpected infection with Helicobacter hepaticus (which may have had an influence on the pathological findings in the liver, as suggested by the authors). Nevertheless the data showed clear effects of RF-EMF exposure on the incidences of lung and liver tumors. We have replicated this study with higher numbers of animals per group, but otherwise under similar conditions, in order to clarify whether the previously reported results could be confirmed. In addition, two additional SAR levels of exposure (low and high) were included in order to investigate possible dose-response relationships. Furthermore, we ensured that we did not have any infection with Helicobacter species in our animals.

... Special care was taken to repeat the study by Tillmann et al. [4] as accurately as possible. Male C3H/HeNCrl (n = 43) and female C57Bl/6N (n = 290) mice were purchased in a staggered design from Charles River Germany, Sulzfeld, Germany, at an age of 8 – 9 weeks. After acclimatization, at the age of 12 weeks (females), the males and 128 females were mated for one week (ratio 3 females: 1 male) in two rounds, thus a total of 256 potentially pregnant females were obtained. They were distributed to the 128 cages of the exposure devices, two animals per cage. Exposure or sham-exposure of the pregnant females thus started at day 6 p.c. (post conception) ...

The exposure devices consisted of eight radial waveguides with 16 cages each, arranged in stacks of two and connected to power amplifiers and RF-generators. Details have been published earlier [5]. Extensive numerical calculations of the field distributions and the corresponding SAR values revealed unavoidable substantial variations for animals in different positions and within animals (local maximum SAR values) which could be as much as 3 – 5 times higher than the whole-body SAR. Two waveguides per exposure group with 16 cages each (32 cages in total, 96 animals) were one out of four groups with the following nominal whole-body SAR levels: sham-exposed (0 W/kg), 0.04 W/kg (low), 0.4 W/kg (moderate) and 2 W/kg (high) for a reference configuration of three mice (body weight 20 g each) per cage, with a standard deviation for this configuration of around 36% ...

As compared to the sham-exposed control mice, numbers of animals with bronchiolo-alveolar adenomas (lungs) were doubled at low and moderate SAR levels, and hepatocellular carcinomas were nearly or more than doubled at low, moderate, and high SAR levels, respectively. The numbers of multiple tumors were found to be significantly elevated at 0.04 W/kg (bronchiolo-alveolar adenomas, Table S1). The numbers of animals with lymphomas were increased 2.5 fold at moderate SAR levels (Fig. 1, Table 1). No increased tumor numbers were found in the brains, kidneys, and spleens of the exposed animals. Here the tumor rates were well below 10%. As expected, survival times in all ENU-treated animals were much lower than in cage controls, but not affected by exposure (Fig. S1). Body weights of (sham-) exposed animals were only slightly different from untreated, unexposed cage-control mice (Fig. S2).

The fact that both studies found basically the same tumor-promoting effects at levels below the accepted (and in most countries legally defined) exposure limits for humans is worrying. Although animal experiments are generally not easily transferable to the situation in humans, the findings are a very clear indication that – in principal – tumor-promoting effects of life-long RF-EMF exposure may occur at levels supposedly too low to cause thermal effects. The basis for defining safety guidelines regarding RF-EMF exposure by mobile phones and other RF-EMF emitting devices relies on the assumption that increases in temperature above a certain threshold are the only way how exposure can cause damage (thermal effects). These are clearly prevented by the exposure limits. However, the RF-EMF energy absorbed by the tissues or organisms, respectively, is converted to thermal energy regardless the exposure dose. As a consequence, this thermal energy influences to some extent the energy balance of tissue and the entire organism. It was shown that RF-EMF exposure at low levels (0.08 W/kg) causes increased body weights in hamsters which indicates a shift in metabolism of food [14]. Other experiments in hamsters have shown that the consumption of food and the production of CO₂ is decreased by RF-EMF exposure, albeit only at relatively high SAR-levels [15]. It is therefore plausible to assume that RF-EMF energy, when absorbed and converted into thermal energy, influences metabolism and energy balance to some extent which may play a role for the observed tumor-promoting effects.

In this context it is important that the carcinogen ENU was administered to the pregnant mice at day 14 of pregnancy. We do not know at which time periods after the treatment with the carcinogen the tumor-promoting effects occurred. Early studies [16] clearly demonstrated that the prenatal time point of ENU-administration is crucial for the development of tumors in the adult. Since the carcinogen was administered to the pregnant females while being already exposed to RF-EMF, it is possible that immediately after ENU-treatment the promoting effects happened. Alternatively, they occurred during the later stages of development. Another possibility why tumor-promoting effects were seen in both studies is that the uptake of the carcinogen by the fetuses was higher in the exposed animals due to elevated metabolism. Studies addressing this question are clearly needed.

The results of our study also stress the importance of exposure conditions in replication studies which are unfortunately often slightly or substantially different from the original studies. For example, Repacholi and co-workers have shown tumor-promoting effects in transgenic mice prone for developing lymphomas [18]. Two replication studies did not confirm these effects [19] and [20]. Both replication studies, however, deviated from the original study in several ways. Not only were the exposure times different, but also were the mice in the replication studies exposed while restrained (in tubes), whereas in the original study the mice were non-restrained. While restrained animals allow exposure at comparably low SAR variations, the physiological and metabolic situations are fundamentally different in comparison to freely moving animals [21]. In fact, the unavoidable SAR variations in non-restrained, freely moving animals may turn out to be of key importance for the understanding of tumor-promoting effects.

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Joel M. Moskowitz, Ph.D., Director
Center for Family and Community Health
School of Public Health
University of California, Berkeley

Electromagnetic Radiation Safety

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