A study of the biological effects of certain ELF electromagnetic fields.
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The hypothesis that the thyroid is the sensitive organ for extremely low freqency electromagnetic field effects was tested. Rats that had been exposed either preinatally or as adults to several intensities of 0.5 Hz magnetic fields displayed no significant alterations in thyroid morphology or circulating hormone measures.
Previous assays with weak sinusoidal magnetic fields (SMF) have shown that bacteria that had been exposed to a 50 Hz magnetic field (0.1-1 mT) gave colonies with significantly lower transposition activity as compared to sham-exposed bacteria. These experiments have now been extended by using a pulsed-square wave magnetic field (PMF) and, unexpectedly, it was found that bacteria exposed to PMF showed a higher transposition activity compared to the controls. The increase of the transposition activity was positively correlated with the intensity of the magnetic fields (linear dose-effect relation). This phenomenon was not affected by any bacterial cell proliferation, since no significant difference was observed in number and size of PMF-exposed and sham-exposed colonies. In addition, the cell viability of E. coli was significantly higher than that of the controls when exposed to SMF, and lower than that of the controls when exposed to PMF. Under our experimental conditions it was shown that exposure to PMF stimulates the transposition activity and reduces cell viability of bacteria, whereas exposure to SMF reduces the transposition mobility and enhances cell viability. These results suggest that the biological effects of magnetic fields may critically depend on the physical characteristics of the magnetic signal, in particular the wave shape.
BACKGROUND: Gastric cancer is the most frequent gastrointestinal cancer in Mexico. Only 33% of cases are resectable. Our aim was to determine the activity and toxicity of the cisplatin, etoposide, leucovorin, and 5-fluorouracil combination in initially unresectable tumors and to determine its ability to permit resection. METHODS: Sixty patients with unresectable gastric adenocarcinoma were treated with cisplatin 80 mg/m2, etoposide 80 mg/m2, leucovorin 25 mg/m2, and 5-fluorouracil 800 mg/m2 by central intravenous catheter for 4 consecutive days. Two courses of this combination were followed by surgical resection. RESULTS: The overall response rate was 36.8% (20 partial responses and one complete response). By using logistic regression analysis, the tumor, node, and metastasis stage (risk ratio, 2.04; 95% confidence interval, 1.03-4.02; P = .039) was identified as the response determinant to chemotherapy. Major toxicity was grade 3 or 4 neutropenia in 67% of patients. Ten resections were performed (17.5%); five were curative and five palliative. Operative morbidity and mortality rates were 40% and 10%, respectively. The median length of survival was 7.46 and 13.3 months for nonresponders and responders, respectively (P = .011). CONCLUSIONS: The cisplatin, etoposide, leucovorin, and 5-fluorouracil combination is active in advanced gastric cancer and the toxicity level is acceptable. This treatment permits a 17.5% resection rate in previously unresectable tumors. A randomized trial of surgery vs. neoadjuvant chemotherapy plus surgery is warranted.
Calcium influx increased during mitogen-activated signal transduction in thymic lymphocytes exposed to a 22 mT, 60 Hz magnetic field (E induced = 1.7 mV/cm, 37 degrees C, 60 min). To distinguish between an electric or a magnetic field dependence a special multi-ring annular cell culture plate based on Faraday's Law of Induction was employed. Studies show a dependence on the strength of the induced electric field at constant magnetic flux density. Moreover, exposure to a pure 60 Hz electric field or to a magnetically-induced electric field of identical strength resulted in similar changes in calcium transport. The first real-time monitoring of [Ca2+]i during application of a 60 Hz electric field revealed an increase in [Ca2+]i observed 100 s after mitogen stimulation; this suggests that the plateau phase rather than the early phase of calcium signaling was influenced. The hypothesis was tested by separating, in time, the early release of calcium from intracellular stores from the influx of extracellular calcium. In calcium-free buffer, 60 Hz field exerted little influence on the early release of calcium from intracellular stores. In contrast, addition of extracellular calcium during exposure enhanced calcium influx through the plasma membrane. Alteration of the plateau phase of calcium signaling implicates the calcium channel as a site of field interaction. In addition, an electric field exposure metric is mechanistically consistent with a cell-surface interaction site.
Oscillations of free intracellular calcium [Ca2+]i were seen in individual Jurkat cells as response to a 50 Hz, 0.15 mT magnetic field (MF). In contrast, a CD45-deficient Jurkat cell line was unable to respond to MF stimulation. The phosphatase activity of CD45 has been implicated to regulate p56lck tyrosine kinase activity by removing an inhibitory phosphate. By using Jurkat cells that expressed a chimeric molecule, comprising the cytoplasmic phosphatase domain of CD45, the MF induced calcium response was restored. This showed the necessity for an intact signal transduction pathway leading to a calcium increase as a result of stimulation of cells by MF. Thus, our data suggest that the target for the applied MF are molecules involved in early events in the signalling pathway from the T cell antigen receptor.
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The incidence of breast cancer in western societies has been rising ever since the Second World War. Besides the exposure to a multitude of new chemical compounds, electromagnetic field exposure has been linked to breast cancer through a radiation-mediated anti-melatonin pathway. We investigated, whether low-frequency electromagnetic field exposure interferes with the anti-estrogenic activity of tamoxifen. Two different clones of the breast cancer cell line MCF-7 were exposed to highly homogeneous 50Hz electromagnetic fields and IC(50) values were calculated from dose-response curves of tamoxifen at various field intensities. An intensity-dependent shift of tamoxifen dose-response curves to higher concentrations with a maximal response at 1.2muT was observed. Hypothetically, electromagnetic field exposure could contribute to tamoxifen resistance observed in breast cancer after long-term treatment.
We have examined the mutational effects of hydrogen peroxide (H(2)O(2)) in the presence and absence of an extremely low-frequency magnetic field (ELFMF), using pTN89 plasmids. Mutations were detected in the supF gene carried by these plasmids in Escherichia coli. The plasmids were either treated with H(2)O(2) (1microM) alone at 37 degrees C for 4h, or were exposed to an ELFMF (60Hz, 5millitesla (mT)) simultaneously with H(2)O(2) treatment. The mutation frequency was 2.28 x 10(-4) for H(2)O(2) treatment alone, and 5.81 x 10(-4) for ELFMF exposure with H(2)O(2) treatment. We did not observe any mutations using treatment with ELFMF exposure alone. This indicates that the ELFMF may potentiate H(2)O(2)-induced mutation. Sequence analysis of the supF mutant plasmids revealed that base substitutions, G: C-->A :T transitions and G:C-->T:A transversions were dominant in both treatment groups, and there was no difference in the mutation spectrum or the hotspots between the groups. Therefore, ELFMFs may interact and potentiate the damage induced by H(2)O(2), resulting in an increase in the number of mutations.
In the present study, we investigated in vitro the possible genotoxic and/or co-genotoxic activity of 50 Hz (power frequency) magnetic fields (MF) by using the alkaline single-cell microgel-electrophoresis (comet) assay. Sets of experiments were performed to evaluate the possible interaction between 50 Hz MF and the known leukemogen benzene. Three benzene hydroxylated metabolites were also evaluated: 1,2-benzenediol (1,2-BD, catechol), 1,4-benzenediol (1,4-BD, hydroquinone), and 1,2,4-benzenetriol (1,2,4-BT). MF (1 mT) were generated by a system consisting of a pair of parallel coils in a Helmholtz configuration. To evaluate the genotoxic potential of 50 Hz MF, Jurkat cell cultures were exposed to 1 mT MF or sham-exposed for 1h. To evaluate the co-genotoxic activity of MF, the xenobiotics (benzene, catechol, hydroquinone, and 1,2,4-benzenetriol) were added to Jurkat cells subcultures at the beginning of the exposure time. In cell cultures co-exposed to 1 mT (50 Hz) MF, benzene and catechol did not show any genotoxic activity. However, co-exposure of cell cultures to 1 mT MF and hydroquinone led to the appearance of a clear genotoxic effect. Moreover, co-exposure of cell cultures to 1 mT MF and 1,2,4-benzenetriol led to a marked increase in the genotoxicity of the ultimate metabolite of benzene. The possibility that 50 Hz (power frequency) MF might interfere with the genotoxic activity of xenobiotics has important implications, since human populations are likely to be exposed to a variety of genotoxic agents concomitantly with exposure to this type of physical agent.
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Possible carcinogenic and/or mutagenic activity of extremely low frequency magnetic fields was examined using somatic mutation and recombination test system of Drosophila melanogaster. An X-linked semi-dominant DNA repair defective mutation mei-41(D5) was introduced into the conventional mwh/flr test system to enhance mutant spot frequency. Virgin females of w mei-41(D5)/FM6; flr/TM6 were crossed with w mei-41(D5)/Y; mwh jv; spa(pol) males. The F(1) third instar larvae were exposed to a 50Hz, 20mT sinusoidal AC magnetic field for 24h. After moulting from pupal cases, their wings were examined under a bright field microscope to detect hair spots with mwh or flr mutant morphology. The exposure caused a statistically significant enhancement in somatic recombination spot frequency. Mutant spots arising due to chromosomal non-disjunction or terminal deletion also increased but the frequency of spots resulting from point mutation was not altered. The enhancement in the recombination spot frequency was suppressed to the control level when a culture medium without electrolytes was used during exposure. When larvae were exposed to a magnetic field in an annular dish, flies from the outer ring showed more mutant spots compared to those from the inner ring. These results suggest that the detected mutagenic activity was that of the induced eddy current, rather than that of the magnetic field itself.