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| 2. |
- Salford, Leif G., et al.
(författare)
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Experimental studies of brain tumour development during exposure to continuous and pulsed 915 MHz radiofrequency radiation
- 1993
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Ingår i: Bioelectrochemistry and Bioenergetics. - 0302-4598. ; 30:C, s. 313-318
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Tidskriftsartikel (refereegranskat)abstract
- It has been suggested that electromagnetic fields (EMFs) act as a promoter late in the carcinogenesis process. To date, however, noconvincing laboratory evidence has been obtained indicating that EMFs cause tumour promotion at non-thermal exposure levels. The effects of EMF exposure in a rat brain glioma model were investigated. The exposure consisted of 915 MHz microwaves, both as continuous waves (1 W), and modulated with 4, 8, 16 and 200 Hz in 0.5 ms pulses and 50 Hz in 6 ms pulses (2 W per pulse). Fischer 344 rats of both sexes, weighing 150-250 g, were used in the experiments. 5000 RG2 cells in 5 μ1 nutrient solution were injected by the stereotaxic technique into the head of the right caudate nucleus in 37 experimental rats and 37 matched controls. The exposed animals were kept unanaesthetized in well ventilated transverse electromagnetic (TEM) cells producing 915 MHz continuous or modulated microwaves. Exposure was started on day five after inoculation. The animals were exposed for 7 hd d-1 for 5 d per week during two to three weeks. The controls were kept in an identical TEM cell without EMF exposure. All brains were examined histopathologically and the tumour size was determined. Our study does not show a significant difference in tumour size between animals exposed to 915 MHz microwaves, and those not exposed. Our preliminary results do not support that even an extensive daily exposure to EMF promotes tumour growth when given from the fifth day after the start of tumour growth in the rat brain until the death of the animal which by then has a large brain tumour. Further studies with higher specific absorption rate levels are in progress.
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| 3. |
- Salford, Leif G., et al.
(författare)
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Permeability of the blood-brain barrier induced by 915 MHz electromagnetic radiation, continuous wave and modulated at 8, 16, 50 and 200 Hz
- 1993
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Ingår i: Bioelectrochemistry and Bioenergetics. - 0302-4598. ; 30:C, s. 293-301
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Tidskriftsartikel (refereegranskat)abstract
- The biological effects of electromagnetic fields (EMFs) on the blood-brain barrier (BBB) can be studied in sensitive and specific models. In a previous investigation of the permeability of the BBB after exposure to the various EMF -components of proton magnetic resonance imaging (MRI), we found that exposure to MRI induced leakage of Evans-blue-labelled proteins which do not normally pass the BBB of rats. In the present investigation we exposed male and female Fischer 344 rats in a TEM cell to 915 MHz microwaves as continuous waves and modulated at various low frequencies (8, 16, 50 and 200 Hz). The rats were not anaesthetized during the exposure. After exposure the brains were perfused first with saline for 3-4 minutes and then with 4% formaldehyde. Central coronal sections of the brains were dehydrated and embedded in paraffin and sectioned at 5 μm. Albumin and fibrinogen were demonstrated immunohistochemically. The results show albumin leakage in 5 out of 62 of the controls and in 56 out of 184 of the animals exposed to 915 MHz microwaves. With continuous waves these are 14 positive findings out of 35 which differs significantly from the results obtained with the controls (p = 0.0002). With pulsed 915 MHz microwaves at modulation frequencies of 200, 50, 16 and 8 Hz, 42 findings out of 149 were positive, which is significant at the p = 0.001 level. This reveals that both continuous and pulsed 915 MHz microwaves are able to open up the BBB for albumin passage. However, there is no significant difference between continuous and pulsed 915 MHz microwaves in this respect. The question of whether the opening of the BBB constitutes a health hazard requires further investigation.
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| 4. |
- Salford, Leif G., et al.
(författare)
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Permeability of the blood‐brain barrier induced by 915 MHz electromagnetic radiation, continuous wave and modulated at 8, 16, 50, and 200 Hz
- 1994
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Ingår i: Microscopy Research and Technique. - : Wiley. - 1059-910X .- 1097-0029. ; 27:6, s. 535-542
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Tidskriftsartikel (refereegranskat)abstract
- Biological effects of electromagnetic fields (EMF) on the blood‐brain barrier (BBB) can be studied in sensitive and specific models. In a previous investigation of the permeability of the blood‐brain barrier after exposure to the various EMF‐components of proton magnetic resonance imaging (MRI), we found that the exposure to MRI induced leakage of Evans Blue labeled proteins normally not passing the BBB of rats [Salford et al. (1992), in: Resonance Phenomena in Biology, Oxford University Press, pp. 87–91]. In the present investigation we exposed male and female Fischer 344 rats in a transverse electromagnetic transmission line chamber to microwaves of 915 MHz as continuous wave (CW) and pulse‐modulated with repetition rates of 8, 16, 50, and 200 s−1. The specific energy absorption rate (SAR) varied between 0.016 and 5 W/kg. The rats were not anesthetized during the 2‐hour exposure. All animals were sacrificed by perfusion‐fixation of the brains under chloral hydrate anesthesia about 1 hour after the exposure. The brains were perfused with saline for 3–4 minutes, and thereafter fixed in 4% formaldehyde for 5–6 minutes. Central coronal sections of the brains were dehydrated and embedded in paraffin and sectioned at 5 μm. Albumin and fibrinogen were demonstrated immunohistochemically. The results show albumin leakage in 5 of 62 of the controls and in 56 of 184 of the animals exposed to 915 MHz microwaves. Continuous wave resulted in 14 positive findings of 35, which differ significantly from the controls (P = 0.002). With pulsed 915 MHz microwaves with repetition rates of 200, 50, 16, and 8 s−1, 42 of 149 were positive, which is highly significant at the P = 0.001 level. This reveals that both CW and pulsed 915 MHz microwaves have the potential to open up the BBB for albumin passage. However, there is no significant difference between continuous and pulsed 915 MHz microwaves in this respect. The frequency of occurrence of extravasates (26%) was found to be independent of SAR for SAR < 2.5 W/kg, but rose significantly for the higher SAR values (to 43%). The question of whether the opening of the blood‐brain barrier constitutes a health hazard demands further investigation. © 1994 Wiley‐Liss, Inc.
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| 6. |
- Ceberg, Crister, et al.
(författare)
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Enhanced boron uptake in RG 2 rat gliomas by electropermeabilization in vivo--a new possibility in boron neutron capture therapy
- 1994
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Ingår i: Anti-Cancer Drugs. - 0959-4973. ; 5:4, s. 463-466
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Tidskriftsartikel (refereegranskat)abstract
- Accumulation of boron in tumor tissue is an indispensable requirement for boron neutron capture therapy and it is important that the uptake is as high as possible. In this work we have studied the influence of electropermeabilization in vivo on the uptake of boron in normal and RG 2 glioma bearing Fischer 344 rats. Two different boron compounds, a sulfhydryl boron hydride (BSH) and a boronated porphyrin (BOPP), have been investigated. The rats were infused intravenously during 5 min with 175 micrograms BSH/g body weight or 12 micrograms BOPP/g body weight. Two electrodes were placed 5 mm apart in the brain and electropermeabilization was performed with eight square 400 V pulses at 4 and 7 min after the end of the infusion. After 6 h the animals were killed, and the boron content in the tumors and the surrounding brain was measured with neutron-activated autoradiography. In electropermeabilized healthy animals the BOPP uptake was low and limited to the electrode lesions, whereas BSH was spread extensively throughout the hemisphere. Rats with gliomas showed doubled (BOPP) to 10-fold (BSH) uptake of boron in the tumor when electropermeabilization was performed as compared with untreated animals. We conclude that electropermeabilization in the future may provide an interesting possibility to increase the uptake of certain boron compounds before neutron capture therapy.
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| 7. |
- Ceberg, Crister, et al.
(författare)
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Neutron capture imaging of 10B in tissue specimens
- 1993
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Ingår i: Radiotherapy and Oncology. - 1879-0887. ; 26:2, s. 139-146
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Tidskriftsartikel (refereegranskat)abstract
- Boron Neutron Capture Therapy (BNCT) is an attractive concept for radiation treatment of malignant tumours. The patients receive a 10B-carrying compound with selective uptake in tumour cells, after which they are irradiated with epithermal neutrons. Theoretically, the tumour cells are killed by the high-LET particles produces in 10B(n, alpha)7Li reactions inside or close to the cell nucleus, while healthy brain cells with no boron uptake will be spared. In practice, a successful BNCT depends on the actual boron-distribution in the tissue, and consequently a new boron-compound aimed for BNCT must undergo detailed bio-distribution studies before clinical trials. In experimental work there is accordingly a great need for methods for quantitative bio-distribution measurements in tissue samples. In this paper we present an improved technique for neutron activated autoradiography providing quantitative boron images of freeze-sectioned tissue specimens from highly malignant rat brain gliomas. Particular attention has been paid to the correlation with the morphology of the specimens and to the altered self-absorption properties due to freeze-drying. A self-absorption correction factor for tumour tissue has been experimentally determined.
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| 8. |
- Salford, Leif, et al.
(författare)
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A new brain tumour therapy combining bleomycin with in vivo electropermeabilization
- 1993
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 194:2, s. 938-943
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Tidskriftsartikel (refereegranskat)abstract
- The potentials of in vivo electropermeabilization in combination with bleomycin in brain tumor treatment have been explored. In the brain of normal Fischer 344 rats, 2 electrodes were placed 5 mm apart. Electropermeabilization was performed with 8 to 12 exponential 400 V pulses with a time constant of 325 microseconds. Some animals were given bleomycin i.v., 1mg/kg b.w., 4 minutes before electric pulses delivery. No adverse effects were recorded during the observation of the animals during the following month. The effect of bleomycin and electropermeabilization upon tumour growth was studied in rats with glioma cells (RG2) implanted in the head of the right caudate nucleus. Treatment was given at different time intervals after the implantation of tumor cells and the effect upon survival was studied. Bleomycin alone did not prolong the survival of the animals. On the contrary, bleomycin plus electropermeabilization on the 10th, 11th or 12th day after inoculation increased the survival time to almost double that of untreated animals. We conclude that this treatment may be of value in brain tumour therapy.
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