Henrietta Nittby

Increased blood–brain barrier permeability in mammalian brain 7 days after exposure to the radiation from a GSM-900 mobile phone

Microwaves were for the first time produced by humans in 1886 when radio waves were broadcasted and received. Until then microwaves had only existed as a part of the cosmic background radiation since the birth of universe. By the following utilization of microwaves in telegraph communication, radars, television and above all, in the modern mobile phone technology, mankind is today exposed to microwaves at a level up to 10(20) times the original background radiation since the birth of universe. Our group has earlier shown that the electromagnetic radiation emitted by mobile phones alters the permeability of the blood-brain barrier (BBB), resulting in albumin extravasation immediately and 14 days after 2h of exposure. In the background section of this report, we present a thorough review of the literature on the demonstrated effects (or lack of effects) of microwave exposure upon the BBB. Furthermore, we have continued our own studies by investigating the effects of GSM mobile phone radiation upon the blood-brain barrier permeability of rats 7 days after one occasion of 2h of exposure. Forty-eight rats were exposed in TEM-cells for 2h at non-thermal specific absorption rates (SARs) of 0mW/kg, 0.12mW/kg, 1.2mW/kg, 12mW/kg and 120mW/kg. Albumin extravasation over the BBB, neuronal albumin uptake and neuronal damage were assessed. Albumin extravasation was enhanced in the mobile phone exposed rats as compared to sham controls after this 7-day recovery period (Fishers exact probability test, p=0.04 and Kruskal-Wallis, p=0.012), at the SAR-value of 12mW/kg (Mann-Whitney, p=0.007) and with a trend of increased albumin extravasation also at the SAR-values of 0.12mW/kg and 120mW/kg. There was a low, but significant correlation between the exposure level (SAR-value) and occurrence of focal albumin extravasation (r(s)=0.33; p=0.04). The present findings are in agreement with our earlier studies where we have seen increased BBB permeability immediately and 14 days after exposure. We here discuss the present findings as well as the previous results of altered BBB permeability from our and other laboratories.

Radiofrequency and extremely low-frequency electromagnetic field effects on the blood-brain barrier.

During the last century, mankind has introduced electricity and during the very last decades, the microwaves of the modern communication society have spread a totally new entity—the radiofrequency fields—around the world. How does this affect biology on Earth? The mammalian brain is protected by the blood-brain barrier, which prevents harmful substances from reaching the brain tissue. There is evidence that exposure to electromagnetic fields at non thermal levels disrupts this barrier. In this review, the scientific findings in this field are presented. The result is a complex picture, where some studies show effects on the blood-brain barrier, whereas others do not. Possible mechanisms for the interactions between electromagnetic fields and the living organisms are discussed. Demonstrated effects on the blood-brain barrier, as well as a series of other effects upon biology, have caused societal anxiety. Continued research is needed to come to an understanding of how these possible effects can be neutralized, or at least reduced. Furthermore, it should be kept in mind that proven effects on biology also should have positive potentials, e.g., for medical use.

Histopathological examinations of rat brains after long-term exposure to GSM-900 mobile phone radiation.

In order to mimic the real life situation, with often life-long exposure to the electromagnetic fields emitted by mobile phones, we have investigated in a rat model the effects of repeated exposures under a long period to Global System for Mobile Communication-900 MHz (GSM-900) radiation. Out of a total of 56 rats, 32 were exposed once weekly in a 2-h period, for totally 55 weeks, at different average whole-body specific absorption rates (SAR) (of in average 0.6 and 60 mW/kg at the initiation of the experimental period). The animals were exposed in a transverse electromagnetic transmission line chamber (TEM-cell) to radiation emitted by a GSM-900 test phone. Sixteen animals were sham exposed and eight animals were cage controls, which never left the animal house. After behavioural tests, 5-7 weeks after the last exposure, the brains were evaluated for histopathological alterations such as albumin extravasation, dark neurons, lipofuscin aggregation and signs of cytoskeletal and neuritic neuronal changes of the type seen in human ageing. In this study, no significant alteration of any these histopathological parameters was found, when comparing the GSM exposed animals to the sham exposed controls.

Radiation immunomodulatory gene tumor therapy of rats with intracerebral glioma tumors.

Abstract Single-fraction radiation therapy with 5 or 15 Gy 60Co γ radiation was combined with intraperitoneal injections of syngeneic interferon gamma (IFN-γ)-transfected cells in rats with intracerebral N29 or N32 glioma tumors at days 7, 21 and 35 after inoculation. For intracerebral N29 tumors, single-fraction radiation therapy with 5 or 15 Gy had no significant effect on the survival time. Immunization with IFN-γ-transfected N29 cells significantly increased the survival time by 61%. Single-fraction radiation therapy with 5 Gy combined with immunization increased the survival time significantly by 87% and complete remissions by 75% while with 15 Gy the survival time increased 45% with 38% complete remissions. For intracerebral N32 tumors, single-fraction radiation therapy with 15 Gy increased the survival time significantly by 20%. Immunization by itself had no significant effect with IFN-γ-transfected N32 cells, but combined with 15 Gy single-fraction radiation therapy it increased survival time significantly by 40%, although there were no complete remissions. Based on these findings, we suggest a new therapeutic regimen for malignant glioma using single-fraction radiation therapy with a target absorbed dose of the order of 5–10 Gy combined with clinically verified immunotherapy.

Photon activation therapy of RG2 glioma carrying Fischer rats using stable thallium and monochromatic synchrotron radiation

75 RG2 glioma-carrying Fischer rats were treated by photon activation therapy (PAT) with monochromatic synchrotron radiation and stable thallium. Three groups were treated with thallium in combination with radiation at different energy; immediately below and above the thallium K-edge, and at 50 keV. Three control groups were given irradiation only, thallium only, or no treatment at all. For animals receiving thallium in combination with radiation to 15 Gy at 50 keV, the median survival time was 30 days, which was 67% longer than for the untreated controls (p = 0.0020) and 36% longer than for the group treated with radiation alone (not significant). Treatment with thallium and radiation at the higher energy levels were not effective at the given absorbed dose and thallium concentration. In the groups treated at 50 keV and above the K-edge, several animals exhibited extensive and sometimes contra-lateral edema, neuronal death and frank tissue necrosis. No such marked changes were seen in the other groups. The results were discussed with reference to Monte Carlo calculated electron energy spectra and dose enhancement factors.

Analgetic effects of non-thermal GSM-1900 radiofrequency electromagnetic fields in the land snail Helix pomatia

Purpose: To investigate whether mobile phone radiation might affect snail nociception, employing radiofrequency (RF) electromagnetic fields (EMF) which, to our knowledge, have hitherto not been studied in a snail model. Exposure to extremely low frequency (ELF) magnetic fields has however been shown to significantly affect nociceptive responses. Materials and methods: In the present study, we exposed 29 land snails of the strain Helix pomatia to global system for mobile communications (GSM) EMF at 1900 MHz at the non-thermal level 48 mW/kg for 1 hour each and 29 snails were sham controls. The experiments took place during the onset of summer, with all snails being well out of hibernation. Before and after GSM or sham exposure, the snails were subjected to thermal pain by being placed on a hot plate. The reaction time for retraction from the hot plate was measured by two blinded observers. Results: Comparing the reaction pattern of each snail before and after exposure, the GSM-exposed snails were less sensitive to thermal pain as compared to the sham controls, indicating that RF exposure induces a significant analgesia (Mann-Whitney p < 0.001). Conclusion: This study might support earlier findings, describing beneficial effects of EMF exposure upon nociception.

Calcium efflux of plasma membrane vesicles exposed to ELF magnetic fieldsutest of a nuclear magnetic resonance interaction model

The question whether very weak, low frequency magnetic fields can affect biological matter is still under debate. The theoretical possibility of such an interaction is often questioned and the site of interaction in the cell is unknown. In the present study, the influence of extremely weak 60 Hz magnetic fields on the transport of Ca(2+) was studied in a biological system consisting of highly purified plasma membrane vesicles. We tested a newly proposed quantum mechanical model postulates that polarization of hydrogen nuclei can elicit a biological effect. Vesicles were exposed for half an hour at 32 °C and the calcium efflux was studied using radioactive (45) Ca(2+) as a tracer. A static magnetic field of 26 µT and time-varying magnetic fields with a frequency of 60 Hz and amplitudes between 0.6 and 6.3 µT were used. The predictions of the model, proposed by Lednev, that at a frequency of 60 Hz the biological effect under investigation would significantly be altered at the amplitudes of 1.3 and 3.9 µT could not be confirmed.

“Abscopal” Effect of Radiation Therapy Combined with Immune-Therapy Using IFN-γ Gene Transfected Syngeneic Tumor Cells, in Rats with Bilateral Implanted N29 Tumors

The tumor growth rate response was studied on N29 rat glioma tumor cells subcutaneously implanted on both hind legs of Fischer-344 rats. At around 30 days after inoculation, RT was given with 60Co gamma radiation with 4 daily fractions of 5 Gy only to the right-lateral tumors. At days 26, 42, and 54 after inoculation, immunization was performed with irradiated syngeneic IFNγ-gene transfected cells. Tumor growth rate (TGR % per day) of the right-lateral irradiated tumor was significantly decreased (𝑃<0.01) after RT alone and with the combination of RT and immunization. But immunization alone gave no significant decrease of the TGR but significantly increased time of survival. The TGR of the unirradiated left-lateral tumors was significantly decreased (𝑃<0.02) only in the group of rats treated with RT alone. It is apparent that tumor cells killed by the radiation mediate suppression of tumor cells outside the target area. This effect is called the abscopal effect.

A GFP Positive Glioblastoma Cell Line NS1 : A New Tool for Experimental Studies

One of the key problems when treating patients with malignant gliomas is that despite being able to remove the major bulk of the tumour, tumour cells may have already spread to distant sites of the brain. The aim of the present study is to develop a GFP positive tumour cell line (named NS1) where these cells could be identified for future treatment studies in fully immunocompetent animals. Five homozygous GFP positive Fischer 344 rats were treated with ENU during pregnancy. Of the offspring, 19 rats developed CNS tumours. Of these, we chose those with tumours growing intracerebrally for further culturing. The tumour cells were transplanted to new recipients. Out of these, we have defined a cell line (NS1), which originated in pons, and reliably generates tumours when transplanted s.c. and i.c. Our new GFP positive cell line was transplanted into GFP negative Fischer 344 rats. The tumours were positive for GFP. With htx-eosin staining, cell rich tumours could be identified both i.c. and s.c. Interestingly, GFAP expression was clear upon i.c. transplantation, but not in the s.c. tumours. The tumour cells had a strong RNA expression for wt IDH1, wt p53, IDO1 and EGFR and to a somewhat smaller extent also to PDL1. Upon irradiation with 8 Gy, IDO1 expression was decreased. With a new GFP positive tumour cell line we have a new tool for investigations of the migrating tumour cells in experimental model. With this, our hope is that treatment protocols will more easily evaluate not only the effect of survival (which is often a limited number of days in animal models) but also whether satellite cells are targeted or not. Of special interest is that the tumour cells can be used in fully immunocompetent animals, meaning that the setting is more similar to a clinical picture.

Zebularine induces long-term survival of pancreatic islet allotransplants in streptozotocin treated diabetic rats.

Background Coping with the immune rejection of allotransplants or autologous cells in patients with an active sensitization towards their autoantigens and autoimmunity presently necessitates life-long immune suppressive therapy acting on the immune system as a whole, which makes the patients vulnerable to infections and increases their risk of developing cancer. New technologies to induce antigen selective long-lasting immunosuppression or immune tolerance are therefore much needed. Methodology/Principal Findings The DNA demethylating agent Zebularine, previously demonstrated to induce expression of the genes for the immunosuppressive enzymes indolamine-2,3-deoxygenase-1 (IDO1) and kynureninase of the kynurenine pathway, is tested for capacity to suppress rejection of allotransplants. Allogeneic pancreatic islets from Lewis rats were transplanted under the kidney capsule of Fischer rats previously made diabetic by a streptozotocin injection (40 mg/kg). One group was treated with Zebularine (225 mg/kg) daily for 14 days from day 6 or 8 after transplantation, and a control group received no further treatment. Survival of the transplants was monitored by blood sugar measurements. Rats, normoglycemic for 90 days after allografting, were subjected to transplant removal by nephrectomy to confirm whether normoglycemia was indeed due to a surviving insulin producing transplant, or alternatively was a result of recovery of pancreatic insulin production in some toxin-treated rats. Of 9 Zebularine treated rats, 4 were still normoglycemic after 90 days and became hyperglycemic after nephrectomy. The mean length of normoglycemia in the Zebularine group was 67±8 days as compared to 14±3 days in 9 controls. Seven rats (2 controls and 5 Zebularine treated) were normoglycemic at 90 days due to pancreatic recovery as demonstrated by failure of nephrectomy to induce hyperglycemia. Conclusions/Significance Zebularine treatment in vivo induces a long-lasting suppression of the immune destruction of allogeneic pancreatic islets resulting in protection of allograft function for more than 10 weeks after end of treatment.