> EMF Health-effects Research

> Lymphomas in E mu-Pim1 transgenic mice exposed to pulsed 900 MHZ electromagnetic fields.

> Repacholi MH, Basten A, Gebski V, Noonan D, Finnie J, Harris AW

> Radiat Res 147(5):631-640, 1997

> Whether radiofrequency (RF) fields are carcinogenic is controversial; epidemiological data have been inconclusive and animal tests limited. The aim of the present study was to determine whether long-term exposure to pulse-modulated RF fields similar to those used in digital mobile telecommunications would increase the incidence oflymphomain E mu-Pim1transgenicmice, which are moderately predisposed to develop lymphoma spontaneously.

> One hundred female E mu-Pim1 mice weresham-exposed and 101 were exposed for two 30-min periods per day for up to 18 months to plane-wave fields of 900 MHz with a pulse repetition frequency of 217 Hz and a pulse width of 0.6 ms. Incident power densities were 2.6-13 W/m2and specific absorption rates were 0.008-4.2 W/kg, averaging 0.13-1.4 W/kg.

> Lymphoma risk was found to be significantly higher in the exposed mice than in the controls (OR= 2.4. P = 0.006, 95% CI = 1.3-4.5).

> Follicular lymphomas were the major contributor to the increased tumor incidence. Thus long-term intermittent exposure to RF fields can enhance the probability that mice carrying a lymphomagenic oncogene will develop lymphomas. We suggest that such genetically cancer-prone mice provide an experimental system for more detailed assessment of dose-response relationships for risk of cancer after RF-field exposure.Additional Web Notes

> This research was funded by Telstra, the Australian carrier, and conducted between 1993 and 1995 (parallel with a 50Hz mains power study). The results were kept secret for two years. Three years later another study is underway by the same group, but funded by the Australian government with Motorola assistance. See index for Royal Adelaide Hospital material in more detail. SF.Another evaluation by an independent UK government scientist

> Comments on Repacholi et al :

> The aim of this study was to determine whether long term exposure to pulse-modulated RF fields (selected specifically to correspond to those used in RF mobile communications) would increase the incidence of lymphoma in transgenic mice. The Em-Pim1 system was chosen because although the mice are moderately predisposed to develop lymphoma spontaneously, for them to acquire malignancy the cells must undergo further mutagenic events in existing genes. Pim1 mice "...would be expected to respond to carcinogenic agents with an increase in lymphomas because (they) express an activated oncogene selectively in the lymphoid cells." The advantage of this system is that it is highly sensitive to mutagenic or carcinogenic influences.

> The result of exposure of the mice under very carefully controlled and characterised conditions was a 2.4 fold increase in the risk of developing lymphoma associated with the exposure. This was highly statistically significant (the statistical probability that the result was due to chance was less than 1%). Furthermore, the lymphomas developed highly significantly earlier in the exposed group than in the unexposed (control) group.

> Much of the paper, especially the Introduction and the Discussion sections, is given over to highlighting the contradictory results and uncertain conclusions which exist in the scientific literature regarding the non-thermal effects of electromagnetic fields. Although this is true, they do not quote several other studies which indicate that microwaves can have a damaging effect on DNA and can alter DNA synthesis, enzyme activity, ion transport, cell proliferation and affect the cell cycle, among other effects. Of relevance are reports of effects on lymphocytes (see Appendix for further details).

> The authors clearly do not regard RF as being able to directly induce mutations or activate genes, so they presumably do not regard RF as a potential carcinogen, even though by their definition in this system it could be regarded as such. Rather they hypothesise that the effect of the exposure is to induce a "transient low level warming of exposed tissues" which leads to increased cell proliferation and therefore to a greater probability of spontaneous lymphomas arising.

> Is this mechanism feasible? Earlier on in the Discussion the authors comment on the subject of heating as follows: "Under the conditions used...the thermal load induced in an exposed mouse would have been small relative to the heat generated by normal metabolic activity". It therefore seems unlikely that such a minute heat load could induce increased cell proliferation. However, it is possible that the RF field may act to induce an increase in cell proliferation by some other mechanism, as has been reported for RF frequencies in lymphocyte cultures (see Cleary et al., 1992). It is also possible that RF exposure may induce the increased expression of an oncogene such asc-fosorc-jun, as has been shown by other workers for extremely low frequency fields.

> It is true that this study does not imply that there is an increased risk to humans of lymphoma induced by mobile phone exposure. It may indicate however that in individuals genetically predisposed to certain forms of cancer, the long term intermittent exposure to RF such as that used in mobile phone technology may be an important environmental stimulus in the induction of malignancy, by an as yet unknown mechanism.

> In order to determine what mechanism is at work in producing these effects, the study would have been enhanced by studying whether there was a difference in the gene expression between the two groups, and importantly, whether RF exposure repeatedly induced the expression of one or more oncogenes. This, along with dose-response studies seems to be a logical extension of the study.

> At the end of the Discussion section the authors imply that an assay system such as this may be useful in determining implications for human health of mobile phone-associated electromagnetic radiation.

> Whilst it is true that there may be a difference between mice and humans in the way they absorb the radiation, this study cannot be dismissed in terms of "it utilised mice therefore it is not relevant to humans". In some cases it is true that mice represent an entirely different biological system to humans, whereas in other cases they are an excellent surrogate for human experiments. In support of the latter cases it should be noted that Australia's most recent winner of the Nobel Prize in Medicine, Prof. Peter Doherty, was awarded the Nobel prize for his work in the immune system using mice. His findings are directly applicable to human biology.

> Secondly, Professor Tony Basten is the Director of the Centenary Institute, and has built his justifiably very fine reputation as a medical researcher in immunology substantially through rodent experiments. It is clear that experiments using laboratory mice can tell us a great deal about how human biology works, that is why they are used in medical research. However, it has yet to be substantiated that in this instance the mice experiments are directly relevant to humans. It is equally important to note that, as yet, that relevance has not been ruled out.

> Dr Shiela Johnson

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