Complex effects of long-term 50 Hz magnetic field exposure in vivo on immune functions in female Sprague-Dawley rats depend on duration of exposure.

In previous studies we have demonstrated that 50 Hz, 100 microT magnetic field (MF) exposure of female Sprague-Dawley rats for 13 weeks significantly enhances the development and growth of mammary tumors in a breast cancer model. The present study was designed to test the hypothesis that, at least in part, the tumor (co)promoting effect of MF exposure is due to MF effects on the immune surveillance system, which is of critical importance in protecting an organism against the development and growth of tumors. For this purpose, female Sprague-Dawley rats of the same age as in the mammary tumor experiments were continuously exposed for different periods (2, 4, 8, and 13 weeks) to a 50 Hz, 100 microT MF. Control groups were sham-exposed simultaneously. Following the different exposure periods, splenic lymphocytes were cultured and the proliferative responses to the T-cell-selective mitogen concanavalin A (Con A) and the B-cell-selective pokeweed mitogen (PWM) were determined. Furthermore, the production of interleukin-1 (IL-1) was determined in the splenocyte cultures. The mitogenic responsiveness of T cells was markedly enhanced after 2 weeks of MF exposure, suggesting a co-mitogenic action of MF. A significant, but less marked increase in T-cell mitogenesis was seen after 4 weeks of MF exposure, whereas no difference from sham controls was determined after 8 weeks, indicating adaptation or tolerance to this effect of MF exposure. Following 13 weeks of MF exposure, a significant decrease in the mitogenic responsiveness of lymphocytes to Con A was obtained. This triphasic alteration in T-cell function (i.e., activation, tolerance, and suppression) during prolonged MF exposure resembles alterations observed during chronic administration of mild stressors, substantiating the hypothesis that cells respond to MF in the same way as they do to other environmental stresses. In contrast to T cells, the mitogenic responsiveness of B cells and IL-1 production of PWM-stimulated cells were not altered during MF exposure. The data demonstrate that MF in vivo exposure of female rats induces complex effects on the mitogenic responsiveness of T cells, which may lead to impaired immune surveillance after long-term exposure.

[1]  P. Garfinkel,et al.  Stress, immunity and illness — a review , 1987, Psychological Medicine.

[2]  L. Kriegsfeld,et al.  Minireview The influence of season, photoperiod, and pineal melatonin on immune function , 1995, Journal of pineal research.

[3]  R. Stevens,et al.  Biologically based epidemiological studies of electric power and cancer. , 1993, Environmental health perspectives.

[4]  O. Smith Cells, stress and EMFs , 1996, Nature Medicine.

[5]  J. Walleczek,et al.  Electromagnetic field effects on cells of the immune system: the role of calcium signaling 1 , 1992, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[6]  F. Dhabhar,et al.  Diurnal and Acute Stress-Induced Changes in Distribution of Peripheral Blood Leukocyte Subpopulations , 1994, Brain, Behavior, and Immunity.

[7]  David Gray,et al.  Immunological Memory and Protective Immunity: Understanding Their Relation , 1996, Science.

[8]  H. Schreiber,et al.  Host-tumor interactions in immunosurveillance against cancer. , 1988, Progress in experimental tumor research.

[9]  T. Mosmann Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. , 1983, Journal of immunological methods.

[10]  R. Faith,et al.  Effects of stress on the immune system. , 1990, Immunology today.

[11]  C. Easterly,et al.  A Meta-Analysis of the Epidemiological Evidence Regarding Human Health Risk Associated with Exposure to Electromagnetic Fields , 1992 .

[12]  K. Skwarło‐Sońta Functional connections between the pineal gland and immune system. , 1996, Acta neurobiologiae experimentalis.

[13]  W. Löscher,et al.  Animal studies on the role of 50/60-Hertz magnetic fields in carcinogenesis. , 1994, Life sciences.

[14]  K. Resch,et al.  T-cell antigen receptor-induced signal-transduction pathways Activation and function of protein kinases C in T lymphocytes , 1995 .

[15]  D. Savitz,et al.  11 – Epidemiologic Evidence on Cancer in Relation to Residential and Occupational Exposures , 1994 .

[16]  W. Löscher,et al.  Exposure of DMBA-treated female rats in a 50-Hz, 50 microTesla magnetic field: effects on mammary tumor growth, melatonin levels, and T lymphocyte activation. , 1996, Carcinogenesis.

[17]  W. Löscher,et al.  A histopathological study on alterations in DMBA-induced mammary carcinogenesis in rats with 50 Hz, 100 muT magnetic field exposure. , 1995, Carcinogenesis.

[18]  J. Gorski,et al.  Embryonic estrogen receptors: do they have a physiological function? , 1995, Environmental health perspectives.

[19]  R. Mandeville,et al.  Differential modulation of natural and adaptive immunity in Fischer rats exposed for 6 weeks to 60 Hz linear sinusoidal continuous-wave magnetic fields. , 1996, Bioelectromagnetics.

[20]  G. Stroink,et al.  Uniform magnetic field produced by three, four, and five square coils , 1983 .

[21]  D. Savitz Overview of occupational exposure to electric and magnetic fields and cancer: Advancements in exposure assessment , 1995 .

[22]  Electromagnetic fields and neoplasms with special reference to extremely low frequencies , 1993 .

[23]  G. Nisticó,et al.  Melatonin increases antigen presentation and amplifies specific and non specific signals for T-cell proliferation. , 1993, International journal of immunopharmacology.

[24]  Y. Touitou,et al.  Sinusoidal 50-Hz magnetic fields depress rat pineal NAT activity and serum melatonin. Role of duration and intensity of exposure. , 1995, Life sciences.

[25]  F. Dhabhar,et al.  Effects of stress on immune cell distribution. Dynamics and hormonal mechanisms. , 1995, Journal of immunology.

[26]  W. Lehmacher,et al.  Tumor promotion in a breast cancer model by exposure to a weak alternating magnetic field. , 1993, Cancer letters.

[27]  Masamichi Kato,et al.  Effects of exposure to a circularly polarized 50-Hz magnetic field on plasma and pineal melatonin levels in rats. , 1993, Bioelectromagnetics.

[28]  W. Löscher,et al.  Study on pineal function and DMBA-induced breast cancer formation in rats during exposure to a 100-mG, 50 Hz magnetic field. , 1996, Journal of toxicology and environmental health.

[29]  Maria A. Stuchly,et al.  Cancer promotion in a mouse-skin model by a 60-Hz magnetic field: II. Tumor development and immune response. , 1991, Bioelectromagnetics.

[30]  A. Khoruts,et al.  The anatomy of T-cell activation and tolerance. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[31]  J. Saffer,et al.  Extremely Low Frequency Electromagnetic Fields and Cancer , 1995 .

[32]  W. R. Rogers,et al.  Initial studies on the effects of combined 60 Hz electric and magnetic field exposure on the immune system of nonhuman primates. , 1995, Bioelectromagnetics.

[33]  R. Liburdy,et al.  Cellular studies and interaction mechanisms of extremely low frequency fields , 1995 .

[34]  S. Persengiev,et al.  Selective effect of melatonin on the proliferation of lymphoid cells. , 1993, The International journal of biochemistry.

[35]  S. Jain,et al.  Enhancement by restraint stress of natural killer cell activity and splenocyte responsiveness to concanavalin A in Fischer 344 rats. , 1991, Immunological investigations.

[36]  A. O'Leary,et al.  Stress, emotion, and human immune function. , 1990, Psychological bulletin.

[37]  P. Murphy,et al.  T cell receptor-independent immunosuppression induced by dexamethasone in murine T helper cells. , 1992, The Journal of clinical investigation.

[38]  M N Bates,et al.  Extremely low frequency electromagnetic fields and cancer: the epidemiologic evidence. , 1991, Environmental health perspectives.

[39]  I. Gery,et al.  POTENTIATION OF THE T-LYMPHOCYTE RESPONSE TO MITOGENS , 1972, The Journal of experimental medicine.

[40]  R P Liburdy,et al.  Nonthermal 60 Hz sinusoidal magnetic‐field exposure enhances 45Ca2+ uptake in rat thymocytes: dependence on mitogen activation , 1990, FEBS letters.

[41]  R. Reiter,et al.  Static and extremely low frequency electromagnetic field exposure: Reported effects on the circadian production of melatonin , 1993, Journal of cellular biochemistry.

[42]  K. Resch,et al.  Inhibition of T lymphocyte activation by cyclosporin A: interference with the early activation of plasma membrane phospholipid metabolism. , 1986, Journal of immunology.

[43]  C. Dinarello,et al.  Characterization of a subclone (D10S) of the D10.G4.1 helper T-cell line which proliferates to attomolar concentrations of interleukin-1 in the absence of mitogens. , 1989, Cytokine.

[44]  W. R. Adey Biological effects of electromagnetic fields , 1993, Journal of cellular biochemistry.

[45]  D A Savitz,et al.  Overview of occupational exposure to electric and magnetic fields and cancer: advancements in exposure assessment. , 1995, Environmental health perspectives.

[46]  U Wahnschaffe,et al.  Effects of weak alternating magnetic fields on nocturnal melatonin production and mammary carcinogenesis in rats. , 1994, Oncology.

[47]  D. Lysle,et al.  Stressor-induced alteration of lymphocyte proliferation in mice: Evidence for enhancement of mitogenic responsiveness , 1990, Brain, Behavior, and Immunity.

[48]  G. Maestroni The immunoneuroendocrine role of melatonin , 1993, Journal of pineal research.

[49]  S. Cohen,et al.  Stress and immunity in humans: a meta‐analytic review. , 1993, Psychosomatic medicine.