The relationship between electromagnetic field and light exposures to melatonin and breast cancer risk: A review of the relevant literature
Corresponding Author
George C. Brainard
Department of Neurology, Jefferson Medical College, Philadelphia, Pennsylvannia
Address reprint requests to George C. Brainard, Ph. D. Department of Neurology Jefferson Medical College, 1025 Walnut Street, Room 310 Philadelphia, PA 19107. E-mail: george.brainardemail.tju.eduSearch for more papers by this authorCorresponding Author
George C. Brainard
Department of Neurology, Jefferson Medical College, Philadelphia, Pennsylvannia
Address reprint requests to George C. Brainard, Ph. D. Department of Neurology Jefferson Medical College, 1025 Walnut Street, Room 310 Philadelphia, PA 19107. E-mail: george.brainardemail.tju.eduSearch for more papers by this authorAbstract
Abstract: Worldwide, breast cancer is the most common malignancy accounting for 20–32% of all female cancers. This review summarizes the peer-reviewed, published data pertinent to the hypothesis that increased breast cancer in industrialized countries is related to the increased use of electricity [Stevens. R. G., S. Davis 1996]. That hypothesis specifically proposes that increased exposure to light at night and electromagnetic fields (EMF) reduce melatonin production. Because some studies have shown that melatonin suppresses mammary tumorigenesis in rats and blocks estrogen-induced proliferation of human breast cancer cells in vitro, it is reasoned that decreased melatonin production leads to increased risk of breast cancer. To evaluate this hypothesis, the paper reviews epidemiological data on associations between electricity and breast cancer, and assesses the data on the effects of EMF exposure on melatonin physiology in both laboratory animals and humans. In addition, the results on the effects of melatonin on in vivo carcinogenesis in animals are detailed along with the controlled in vitro studies on melatonin's effects on human breast cancer cell lines. The literature is evaluated for strength of evidence, inter-relationships between various lines of evidence, and gaps in our knowledge. Based on the published data, it is currently unclear if EMF and electric light exposure are significant risk factors for breast cancer, but further study appears warranted. Given the ubiquitous nature of EMF and artificial light exposure along with the high incidence of breast cancer. even a small risk would have a substantial public health impact.
Literature cited
- Ader, R., D. Felten, N. Cohen (1990) Interactions between the brain and the immune system. Annu. Rev. Pharmacol. Toxicol. 30: 561–602.
- Arendt, J. (1995) Melatonin and the Mammalian Pineal Gland. Chapman and Hill, London , pp. 1–331.
- Arnetz, B. B., M. Berg (1996) Melatonin and adrenocorticotropic hormone levels in video display unit workers during work and leisure. J. Occup. Environ. Med. 38: 1108–1110.
- Aschoff, J. (1981) Handbook of Behavioral Neurobiology. Biological Rhythms. Plenum Press, New York , pp. 1–563.
- Aubert, C., P. Janiaud, J. Lecalvez (1980) Effect of pinealectomy and melatonin on mammary tumor growth in Sprague-Dawley rats under different conditions of lighting. J. Neural Transm. 47: 121–130.
- Bailey, W. H., S. H. SU. T. D. Bracken, R. Kavet (1997) Summary and evaluation of guidelines for occupational exposure to power frequency electric and magnetic fields. Health Phys. 73: 433–453.
- Bakos, J., N. Nagy, G. Thuroczy, L. Szabo (1995) Sinusoidal 50 Hz. 500 μT magnetic field has no acute effect on urinary 6-sulphatoxymelatonin in wistar rats. Bioelectromagnetics 16: 377–380.
- Bakos, J., N. Nagy, G. Thuroczy, L. Szabo (1997) Urinary 6-sulphatoxymelatonin excretion is increased in rats after 24 hours of exposure to vertical 50 Hz. 100 μT magnetic field. Bioelectromagnetics 18: 190–192.
- Bartsch, C., H. Bartsch, A. Buchberger, A. Stieglitz, D. Mecke. T. H. Lippert (1994a) Serial transplants of DMBA-induced mammary tumours in Fischer rats as model system for human breast cancer: II. Analysis of pineal melatonin biosynthesis and secretion. Adv. Pineal Res. 8: 479–484.
- Bartsch, C., H. Bartsch. A. Buchberger, H. Rokos, D. Mecke, T. H. Lippert (1995) Serial transplants of DMBA-induced mammary tumors in Fischer rats as model system for human breast cancer. IV. Parallel changes of biopterin and melatonin interactions between the pineal gland and cellular immunity in malignancy. Oncology 52: 278–283.
- Bartsch, H., C. Bartsch, W. E. Simon, B. FLEHMIG. I. Ebels, T. H. Lippert (1992) Antitumor activity of the pineal gland: Effect of unidentified substances versus the effect of melatonin. Oncology 49: 27–30.
- Bartsch, H., C. Bartsch, D. Mecke, T. H. Lippert (1994b) Serial transplants of DMBA-induced mammary tumours in Fischer rats as model system for human breast cancer: I. Effect of melatonin and pineal extracts on slow- and fast-growing passages-in vivo and in vitro studies. Adv. Pineal Res. 8: 473–478.
- Blask, D. E. (1993) Melatonin in oncology. In: Melatonin: Biosynthesis, Physiological Effects, and Clinical Applications, H. S. Yu, R. J. Reiter, eds. CRC Press, Boca Raton , FL , pp. 447–475.
- Blask, D. E. (1997) Systemic, cellular, and molecular aspects of melatonin action on experimental breast carcinogenesis. In: The Melatonin Hypothesis: Breast Cancer and Use of Electric Power, R. G. Stevens, B. W. Wilson, L. E. Anderson, eds. Battelle Press, Columbus , OH , pp. 189–230.
- Blask, D. E., S. M. Hill (1986) Effects of melatonin on cancer: studies on MCF-7 human breast cancer cells in culture. J. Neural Transm. 21: 433–449.
- Blask, D. E., S. M. Hill, K. M. Orstead, J. S. Massa (1986) Inhibitory effects of the pineal hormone melatonin and underfeeding during the promotional phase of 7.12-dimethyl-benzanthracene-(DMBA)-induced mammary tumorigenesis. J. Neural Transm. 67: 125–138.
- Blask, D. E., D. B. Pelletier. S. M. Hill, A. Lemuswilson, D. S. Grosso, D. T. Wilson, M. E. Wise (1991) Pineal melatonin inhibition of tumor promotion in the N-nitroso-N-methylurea model of mammary carcinogenesis: Potential involvement of antiestrogenic mechanisms in vivo. J. Cancer Res. Clin. Oncol. 117: 526–532.
- Blask, D. E., S. T. Wilson, F. Zalatan (1997) Physiological melatonin inhibition of human breast cancer cell growth in vitro: Evidence for a glutathione-mediated pathway. Cancer Res. 57: 1909–1914.
- Bracken, T. D., R. S. Senior, R. F. Rankin, W. H. Bailey, R. Kavet (1997) Magnetic field exposures in the electric utility industry relevant to occupational guideline levels. Appl. Occup. Environ. Hyg. 12: 756–768.
10.1080/1047322X.1997.10387760 Google Scholar
- Brainard, G. C., J. R. Gaddy, F. L. Ruberg, F. M. Barker, J. P. Hanifin, M. D. Rollag (1994) Ocular mechanisms that regulate the human pineal gland. In: Advances in Pineal Research. M. Møller, P. Pévet, eds. Vol. 8. John Libby, London , pp. 415–432.
- Brainard, G. C., M. D. Rollag. J. P. Hanifin (1997) Photic regulation of melatonin in humans: Ocular and neural signal transduction. J. Biol. Rhythms 12: 537–546.
- Brzezinski, A. (1997) Melatonin in humans. N. Engl. J. Med. 336: 186–195.
- Buxton, O. M., M. L'HERMITE-BALÉRIAUX, U. Hirschfeld, E. VAN Cauter (1997) Acute and delayed effects of exercise on human melatonin secretion. J. Biol. Rhythm 12: 568–574.
- Cammarano, G., P. Crosignani, F. Berrino, G. Berra (1984) Cancer mortality among workers in a thermoelectric power plant. Scand. J. Work Environ. Health 10: 259–261.
- Cantor, K. P., M. Dosemeci, L. A. Brinton, P. A. Stewart (1995) Breast cancer mortality among female electrical workers in the United States (letter). J. Natl. Cancer Inst. 87: 227–228.
- Caroleo, M. C., D. Frasca, G. Nistico, G. Doria (1992) Melatonin as immunomodulator in immunodeficient mice. Immunopharmacology 23: 81–89.
- Cassone, V. M. (1990) Effects of melatonin on vertebrate circadian systems. Trend Neurosci. 13: 457–464.
- Chang, N., T. S. Spaulding, M. T. Tseng (1985) Inhibitory effects of superior cervical ganglionectomy on dimethyl-bez[a]anthracene-induced mammary tumors in the rat. J. Pineal Res. 2: 331–340.
- Chang, N., M. T. Tseng, T. S. Spaulding (1986) Induction and growth of mammary tumors after superior cervical ganglionectomy in sighted and blinded-anosmic rats. Life Sci. 38: 1821–1826.
- Cohen, M., M. Lippman, B. Chabner (1978) Role of pineal gland in aetiology and treatment of breast cancer. Lancet 2: 814–816.
- Collin, J. P., A. Oksche (1981) Structural and functional relationships in the nonmammalian pineal gland. In: The Pineal Gland. Anatomy and Biochemistry, R. J. Reiter, ed. Vol. 1. CRC Press, Boca Raton , FL , pp. 27–67.
- Coogan, P. F., R. W. Clapp, P. A. Newcomb, T. B. Wenzl, G. Bogdan, R. MlTTENDORF, J. A. Baron, M. P. Longnecker (1996) Occupational exposure to 60-Hertz magnetic fields and risk of breast cancer in women. Epidemiology 7: 459–464.
- Cos, S., D. E. Blask (1990) Effects of the pineal hormone melatonin on the anchorage-independent growth of human breast cancer cells (MCF-7) in a clonogenic culture system. Cancer Lett. 50: 115–119.
- Cos, S, E. J. Sanchez-Barcelo (1994) Differences between pulsatile or continuous exposure to melatonin on MCF-7 human breast cancer cell proliferation. Cancer Lett. 85: 105–109.
- Cos, S., D. E. Blask (1994) Melatonin modulates growth factor activity in MCF-7 human breast cancer cells. J. Pineal Res. 17: 25–32.
- Cos, S., E. J. Sanchez-Barcelo (1995) Melatonin inhibition of MCF-7 human breast-cancer cells growth: Influence of cell proliferation rate. Cancer Lett. 93: 207–212.
- Cos, S., F. Garijo, J. Corral, M. D. Mediavilla, E. J. Sanchez-Barcelo (1989) Histopathologic features of DMBA-induced mammary tumors in blind-underfed, blind-anosmic, and blind cold-exposed rates: Influence of the pineal gland. J. Pineal Res. 6: 221–231.
- Cos, S., D. E. Blask, A. Lemus-Wilson, A. B. Hill (1991) Effects of melatonin on the cell cycle kinetics and ‘estrogen-rescue’ of MCF-7 human breast cancer cells in culture. J. Pineal Res. 10: 36–42.
- Cos, S., J. Recio, E. J. Sanchez-Barcelo (1996a) Modulation of the length of the cell cycle time of MCF-7 human breast cancer cells by melatonin. Life Sci. 58: 811–816.
- Cos, S., F. Fernandez, E. J. Sanchez-Barcelo (1996b) Melatonin inhibits DNA synthesis in MCF-7 human breast cancer cells in vitro. Life Sci. 58: 2447–2453.
- Cremer-Bartels, G., K. Krause, H. J. KÜCHLE (1983) Influence of low magnetic-field-strength variations on the retina and pineal gland of quail and humans. Graefes Arch. Clin. Exp. Ophthalmol. 220: 248–252.
- Crespo, D., R. Fernandez-Viadero, R. Verdliga, V. Ove-Jero, S. Cos (1994) Interaction between melatonin and estradiol on morphological and morphometric features of MCF-7 human breast cancer cells. J. Pineal Res. 16: 215–222.
- DEL Gobbo, V., V. Libri, N. VlLLANI, R. Callio, G. Nistico (1989) Pinealectomy inhibits interleukin-2 production and natural killer activity in mice. Int. J. Immunopharmac. 11: 567–573.
- Demers, P. A., D. B. Thomas, K. A. Rosenblatt, L. M. Jimenez, A. Mctiernan, H. Stalsberg, A. Stemhagen, W. D. Thompson, M. G. Curnen, W. Satariano, D. F. Austin. P. Isacson, R. S. Greenberg, C. Key, L. N. Kolonel, D. W. West (1991) Occupational exposure to electromagnetic fields and breast cancer in men. Am. J. Epidemiol. 134: 340–347.
- Eakin, R. M. (1973) The Third Eye. University of California Press, Berkeley , CA , pp. 1–157.
- Floderus, B., S. Tornqvist, C. Stenlund (1994) Incidence of selected cancers in Swedish Railway workers, 1961–79. Cancer Causes Control 5: 189–194.
- Furuya, Y., K. Yamamoto, N. Kohno. Y. KU. Y. Saitoh (1994) 5-Fluorouracil attenuates an oncostatic effect of melatonin on estrogen-sensitive human breast cancer cells (MCF-7). Cancer Lett. 81: 95–98.
- Gammon, M. D., J. B. Schoenberg. J. A. Britton, J. L. Kelsey, J. L. Stanford. K. E. Malone. R. J. Coates, D. J. Brogan. N. Potischman, C. A. Swanson. L. A. Brinton (1998) Electric blanket use and breast cancer risk among younger women. Am. J. Epidemiol. 148: 556–563.
- Graham, C. (1998) Biological effects of static and ELF fields. In: Interactions of Static and Extremely Low Frequency Electric and Magnetic Fields on Living Systems. R. Matthes, J. Bernhardt, M. H. Repacholi, eds. International Commission on Non-Ionizing Radiation Protection (ICNIRP), Munich , Germany , pp. 171–186.
- Graham, C, M. R. Cook, D. W. Riffle (1996) Human melatonin during continuous magnetic field exposure. Bioelectro-magnetics 18: 166–171.
- Graham, C., M. R. Cook, D. W. Riffle, M. M. Gerkovich, H. D. Cohen (1997) Nocturnal melatonin levels in human volunteers exposed to intermittent 60 Hz magnetic fields. Bioelectromagnetics 17: 263–273.
- Graham. C., M. R. Cook. R. Kavet. A. Sastre. D. K. Smith (1998) Prediction of nocturnal plasma melatonin from morning urinary measures. J. Pineal Res. 24: 230–238.
- Grota, L. J., R. J. Reiter, P. K. Eng. S. Michaelson (1994) Electric field exposure alters serum melatonin but not pineal melatonin synthesis in male rats. Bioelectromagnetics 15: 427–437.
- Guberan, E., M. Usel, L. Raymond, R. TlSSOT, P. M. Sweetnam (1989) Disability, mortality, and incidence of cancer among Geneva painters and electricians: A historical prospective study. Br. J. Ind. Med. 46: 16–23.
- Guenel, P., P. Raskmark, J. B. Andersen. E. Lynge (1993) Incidence of cancer in persons with occupational exposure to electromagnetic fields in Denmark. Br. J. Ind. Med. 50: 758–764.
- Hahn, R. (1991) Profound bilateral blindness and the incidence of breast cancer. Epidemiology 2: 208–210.
- Hamilton, T. (1969) Influence of environmental light and melatonin upon mammary tumour induction. Brit. J. Surg. 56: 764–766.
- Harland, J. D., R. P. Liburdy (1997) Environmental magnetic fields inhibit the antiproliferative action of tamoxifen and melatonin in a human breast cancer cell line. Bioelectromag-netics 18: 555–562.
- Hill, S. M., D. E. Blask (1988) Effects of the pineal hormone melatonin on the proliferation and morphological characteristics of human breast cancer cells (MCF-7) in culture. CanT cer Res. 48: 6121–6126.
- Hill, S. M., L. L. Spriggs, M. A. Simon, H. Muraoka, D. E. Blask (1992) The growth inhibitory action of melatonin on human breast cancer cells is linked to the estrogen response system. Cancer Lett. 64: 249–256.
- Jentsch, A., M. Lehmann, E. Schöne, F. Thoss, G. Zimmermann (1993) Weak magnetic fields change extinction of a conditioned reaction and daytime melatonin levels in the rat. Neurosci. Lett. 157: 79–82.
- Kato, M., K. Honma, T. Shigemitsu. Y. Shiga (1993) Effects of exposure to a circularly polarized 50-Hz magnetic field on plasma and pineal melatonin levels in rats. Bioelec-tromagnetics 14: 97–106.
- Kato, M., K. Honma, T. Shigemitsu, Y. Shiga (1994a) Circularly polarized 50 Hz magnetic field exposure reduces pineal gland and blood melatonin concentrations of Long-Evans rats. Neurosci. Lett. 166: 59–62.
- Kato, M., K. Honma, T. Shigemitsu, Y. Shiga (1994b) Horizontal or vertical 50-Hz, l-microT magnetic fields have no effect on pineal gland or plasma melatonin concentration of albino rats. Neurosci. Lett. 168: 205–208.
- Kato, M., K. Honma. T. Shigemitsu, Y. Shiga (1994c) Recovery of nocturnal melatonin concentration takes place within week following cessation of 50 Hz circularly polarized magnetic field exposure for six weeks. Bioelectromagnetics 15: 489–492.
- Kaune, W. T., R. D. Phillips (1980) Comparison of the coupling of grounded humans, swine and rats to vertical, 60-hz electric fields. Bioelectromagnetics 1: 117–129.
- Kaune, W. T., L. E. Anderson (1990) Physical aspects of ELF electric and magnetic fields: measurements and dosime-try. In: Extremely Low Frequency Electromagnetic Fields: The Question of Cancer, B. W. Wilson, R. G. Stevens, L. E. Anderson, eds. Battelle Press, Columbus , OH , pp. 17–45.
- Kavet, R. (1996) EMF and current cancer concepts. Bioelectromagnetics 17: 339–357.
- Kelsey, J. L., L. Bernstein (1996) Epidemiology and prevention of breast cancer. Annu. Rev. Public Health 17: 47–67.
- Kelsh, M. A., J. D. Sahl (1997) Mortality among a cohort of electrical utility workers, 1960–1991. Am. J. Ind. Med. 31: 534–544.
10.1002/(SICI)1097-0274(199705)31:5<534::AID-AJIM6>3.0.CO;2-T CASPubMedWeb of Science®Google Scholar
- Khoory, R. (1987) Compensation of the natural magnetic field does not alter N-acetyltransferase activity and melatonin content of rat pineal gland. Neurosci. Lett. 76: 215–220.
- Klein, D. C., J. L. Weller (1972) Rapid light-induced decrease in pineal serotonin N-acetyltransferase activity. Science 177: 532–533.
- D. C. Klein, R. Y. Moore. S. M., Reppert, eds. (1991) Suprachiasmatic Nucleus: The Mind's Clock. Oxford University Press, Oxford , pp. 5–456.
- Kojima, T., C. Mochizuki, T. MlTAKA, Y. Mochizuki (1997) Effects of melatonin on proliferation, oxidative stress and Cx32 gap junction protein expression in primary cultures of adult rat hepatocytes. Cell. Struct. Funct. 22: 347–356.
- Korf, H. W. (1996) Innervation of the pineal gland. In: The Autonomic Nervous, K. Unsicker, ed. System Harwood Academic Publishers, Amsterdam , pp. 129–180.
- Kothari, A., A. Borges, L. Kothari (1995) Chemopreven-tion by melatonin and combined melatonin-tamoxifen therapy of second generation nitroso-methylurea-induced mammary tumour in rats. Eur. J. Cancer Prev. 4: 497–500.
- Kothari, A., A. Borges, A. Ingle, L. Kothari (1997) Combination of melatonin and tamoxifen as ‘a chemopro-phylaxis against N-nitroso-N-methylurea-induced rat mammary tumors. Cancer Lett. 111: 59–66.
- Kothari, L. S. (1987) Influence of chronic melatonin on 9,10-dimethyl-l, 2, benzanthracene-induced mammary tumors in female Holtzman rats exposed to continuous light. Oncology 44: 64–66.
- Kothari, L., A. Subramanian (1992) A possible modula-tory influence of melatonin on representative phase I and II drug metabolizing enzymes in 9, 10-dimethyl-l, 2-benzan-thracene induced rat mammary tumorigenesis. Anticancer Drugs 3: 623–628.
- Kothari, L. S., P. N. Shah, M. C. Mhatre (1982) Effect of continuous light on the incidence of 9, 10-dimethyl-1, 2-ben-zanthracene induced mammary tumors in female Holtzman rats. Cancer Lett. 16: 313–317.
- Kothari, L. S., P. N. Shah, M. C. Mhatre (1984) Pineal ablation in varying photoperiods and the incidence of 9, 10-dimethyl-1, 2-benzanthracene induced mammary cancer in rats. Cancer Lett. 22: 99–102.
- Lambrozo, J., Y. Touitou, W. Dab (1996) Exploring the EMF-melatonin connection: A review of the possible effects of 50/60-Hz electric and magnetic fields on melatonin secretion. Int J Occup Environ Health 2: 37–47.
- Laporte, R., L. Kus, R. A. Wisniewski. M. M. Prechel, B. Azar-Kla, J. A. Mcnulty (1990) Magnetic resonance imaging (MRI) effects on rat pineal neuroendocrine function. Brain Res. 506: 294–296.
- Lee, J. M. J., F. Stormshak, J. M. Thompson. P. Thinesen, L. J. Painter, E. G. Olenchek, D. L. Hess. R. Forbes. D. L. Foster (1993) Melatonin secretion and puberty in female lambs exposed to environmental electric and magnetic fields. Biol. Reprod. 49: 857–864.
- Lee, J. M. J., F. Stormshak, J. M. Thompson, D. L. Hess, D. L. Foster (1995) Melatonin and puberty in female lambs exposed to EMF: A replicate study. Bioelectromagnetics 16: 119–123.
- Lemus-Wilson, A, P. A. Kelly, D. E. Blask (1995) Melatonin blocks the stimulatory effects of prolactin on human breast cancer cell growth in culture. Br. J. Cancer 72: 1435–1440.
- Leone, A. M., D. Skene (1994) Melatonin concentrations in pineal organ culture are suppressed by sera from tumor-bearing mice. J. Pineal Res. 17: 17–19.
- Lerchl, A., K. O. Nonaka, K. A. Stokkan, R. J. Reiter (1990) Marked rapid alterations in nocturnal pineal serotonin metabolism in mice and rats exposed to weak intermittent magnetic fields. Biochem. Biophys. Res. Commun. 169: 102–108.
- Lerchl, A., K. O. Nonaka, R. J. Reiter (1991a) Pineal gland ‘magnetosensitivity’ to static magnetic fields is a consequence of induced electric currents (eddy currents). J. Pineal Res. 10: 109–116.
- Lerchl, A., R. J. Reiter, K. A. Howes, K. O. Nonaka, K. A. Stokkan (1991b) Evidence that extremely low frequency Ca2 + -cyclotron resonance depresses pineal melatonin synthesis in vitro. Neurosci. Lett. 124: 213–215.
- Levenson, A. S., V. C. Jordan (1997) MCF-7: The first hormone-responsive breast cancer cell line. Cancer Res. 57: 3071–3078.
- Levine, R. L., J. K. Dooley, T. D. Bluni (1995) Magnetic field effects on spatial discrimination and melatonin levels in mice. Physiol. Behav. 58: 535–537.
- Lewy, A. J., T. A. Wehr, F. K. Goodwin, D. A. Newsome, S. P. Markey (1980) Light suppresses melatonin secretion in humans. Science 210: 1267–1269.
- L'HERMITE-BALÉRIAUX. M., Y DE Launoit (1992) Is melatonin really an in vitro inhibitor of human breast cancer cell proliferation? (letter). In Vitro Cell Dev Biol 28A: 583–584.
- Li, C. Y., G. Theriault. R. S. Lin (1997) Residential exposure to 60-Hertz magnetic fields and adult cancers in Taiwan. Epidemiology 8: 25–30.
- Liburdy. R. P., T. R. Sloma. R. Sokolic, P., Yaswen (1993) ELF magnetic fields, breast cancer, and melatonin: 60 Hz fields block melatonin's oncostatic action on ER + breast cancer cell proliferation. J. Pineal Res. 14: 89–97.
- Loomis, D. P. (1992) Cancer of breast among men in electrical occupations (letter). Lancet 339: 1482–1483.
- Loomis, D. P., D. A. Savitz, C. V. Ananth (1994) Breast cancer mortality among female electrical workers in the United States. J. Natl. Cancer Inst. 86: 921–925.
- Loscher, W., U. Wahnschaffe, M. Mevissen, A. Lerchl, A. Stamm (1994) Effects of weak alternating magnetic fields on nocturnal melatonin production and mammary carcino-genesis in rats. Oncology 51: 288–295.
- Maestroni, G. J. M. (1993) The immuno-neuroendocrine role of melatonin. J. Pineal Res. 14: 1–10.
- Maestroni, GJ. M. (1995) T-Helper-2 lymphocytes as a peripheral target of melatonin. J. Pineal Res. 18: 84–89.
- Maestroni, G. J. M., A. Conti (1989) Beta-endorphin and dynorphin mimic the circadian immunoenhancing and antistress effects of melatonin. Int. J. Immunopharmac. 11: 333–340.
- Maestroni, G. J. M., A. Conti (1990) The pineal neurohor-mone melatonin stimulates activated CD4 +, Thy-1 + cells to release opioid agonist(s) with immunoenhancing and anti-stress properties. J. Neuroimmunol. 28: 167–176.
- Maestroni, G. J. M., A. Conti (1991) Anti-stress role of the melatonin-immuno-opioid network: Evidence for a physiological mechanism involving T cell-derived, immuno-reactive fl-endorphin and metenkephalin binding to thymic opioid receptors. Intern. J. Neurosci. 61: 289–298.
- Maestroni, G. J. M., A. Conti, W. Pierpaoli (1986) Role of the pineal gland in immunity: Circadian synthesis and release of melatonin modulates the antibody response and antagonizes the immunosuppressive effect of corticosterone. J. Neuroimmunol. 13: 19–30.
- Maestroni, GJ. M., A. Conti, W. Pierpaoli (1987) Role of the pineal gland in immunity: II. Melatonin enhances the antibody response via an opiatergic mechanism. Clin. Exp. Immunol. 68: 384–391.
- Maestroni, G. J. M., A. Conti, W. Pierpaoli (1988) Role of the pineal gland in immunity: III. Melatonin antagonizes the immunosuppressive effect of acute stress via an opiatergic mechanism. Immunology 63: 465–469.
- Maestroni, G. J. M., A. Conti, P. Lissoni (1994a) Colony-stimulating activity and hematopoietic rescue from cancer chemotherapy compounds are induced by melatonin via endogenous interleukin 4. Cancer Res. 54: 4740–4743.
- Maestroni, G. J. M., V. Covacci, A. Conti (1994b) Hematopoietic rescue via T-cell-dependent, endogenous granulo-cyte-macrophage colony-stimulating factor induced by the pineal neurohormone melatonin in tumor-bearing mice. Cancer Res. 54: 2429–2432.
- Martinez , SORIANO F., M. Gimenez Gonzalez, E. Armanazas, A. RUIZ Turner (1992) Pineal ‘synaptic ribbons’ and serum melatonin levels in the rat following the pulse action of 52-Gs (50-Hz) magnetic fields: An evolutive analysis over 21 days. Acta Anat. 143: 289–293.
10.1159/000147264 Google Scholar
- Matanoski, G. M., P. N. Breysse, E. A. Elliott (1991) Electromagnetic field exposure and male breast cancer (letter). Lancet 337: 737.
- Mcdowall, M. E. (1986) Mortality of persons resident in the vicinity of electricity transmission facilities. Br. J. Cancer 53: 271–279.
- Mediavilla, M. D., M. San Martin, E. J. Sanchez-Barcelo (1992) Melatonin inhibits mammary gland development in female mice. J. Pineal Res. 13: 13–19.
- Mediavilla, M. D., A. Guezmez, S. Ramos, L. Kothari, F. Garijo, E. J. Sanchez-Barcelo (1997) Effects of melatonin on mammary gland lesions in transgenic mice overex-pressing N-ras proto-oncogene. J. Pineal Res. 22: 86–94.
- Mevissen, M., A. Lerchl, M. Szamel, W. Loscher (1996a) Exposure of DMBA-treated female rats in a 50-Hz, 50 μ Tesla magnetic field: Effects on mammary tumor growth, melatonin levels, and T lymphocyte activation. Carcinogenesis 17: 903–910.
- Mevissen, M., A. Lerchl, W. Loscher (1996b) Study on pineal function and DMBA-induced breast cancer formation in rats during exposure to a 100 mG, 50 Hz magnetic field. J. Toxicol. Environ. Health 48: 169–185.
- Mhatre, M., P. Shah, H. Juneja (1984) Effect of varying photoperiods on mammary morphology, DNA synthesis, and hormone profile in female rats. J Natl Cancer Inst. 72: 1411–1416.
- Milham JR., S. (1985) Mortality in workers exposed to electromagnetic fields. Environ. Health Perspect. 62: 297–300.
- Molis, T. M., M. R. Walters, S. M. Hill (1993) Melatonin modulation of estrogen receptor expression in MCF-7 human breast cancer cells. Int. J. Oncol. 3: 687–694.
- Molis, T. M., L. L. Spriggs, S. M. Hill (1994) Modulation of estrogen receptor mRNA expression by melatonin in MCF-7 human breast cancer cells. Mol. Endocrinol. 8: 1681–1690.
- Molis, T. M., L. L. Spriggs, Y. Jupiter, S. M. Hill (1995) Melatonin modulation of estrogen-regulated proteins, growth factors, and proto-oncogenes in human breast cancer. J. Pineal Res. 18: 93–103.
- Moore, R. Y., J. C. Speh, J. P. Card (1995) The retinohypo-thalamic tract originates from a distinct subset of retinal ganglion cells. J. Comp. Neurol. 352: 351–366.
- NATIONAL RESEARCH COUNCIL (1997) Possible Health Effects of Exposure to Residential Electric and Magnetic Fields. National Academy Press, Washington , DC , pp. 1–356.
- Olcese, J. M. (1990) The neurobiology of magnetic field detection in rodents. Prog. Neurobiol. 35: 325–330.
- Olcese, J., S. Reuss (1986) Magnetic field effects on pineal gland melatonin synthesis: Comparative studies on albino and pigmented rodents. Brain Res. 369: 365–368.
- Olcese, J., S. Reuss, L. Vollrath (1985) Evidence for the involvement of the visual system in mediating magnetic field effects on pineal melatonin synthesis in the rat. Brain Res. 333: 382–384.
- Olin, R., D. Vagero, A. Ahlbom (1985) Mortality experience of electrical engineers. Br. J. Ind. Med. 42: 211–212.
- Osborne, C. K., K. Hobbs, J. M. Trent (1987) Biological differences among MCF-7 human breast cancer cell lines from different laboratories. Breast Cancer Res. Treat. 9: 111–121.
- Panzer, A., M. Viljoen (1997) The validity of melatonin as an oncostatic agent. J. Pineal Res. 22: 184–202.
- Panzer, A., M. L. Lottering, P. Bianchi, D. K. Glen-Cross, J. H. Stark, J. C. Seegers (1998) Melatonin has no effect on the growth, morphology or cell cycle of human breast cancer (MCF-7), cervical cancer (HeLa), osteosar-coma (MG-63) or lymphoblastoid (TK6) cells. Cancer Lett 122: 17–23.
- Parkin, D. M., P. Pisani, J. Ferlay (1993) Estimates of the worldwide incidence of eighteen major cancers in 1985. Int. J. Cancer 54: 594–606.
- Pearce, N., J. Reif, J. Fraser (1989) Case-control studies of cancer in New Zealand electrical workers. Int. J. Epidemiol, 18: 55–59.
- Perlow, M. J., S. M. Reppert, L. Tamarkin, R. J. Wyatt, D. C. Klein (1980) Photic regulation of the melatonin rhythm: Monkey and man are not the same. Brain Res. 182: 211–216.
- Pfluger, D. H., C. E. Minder (1996) Effects of exposure to 16.7 Hz magnetic fields on urinary 6-hydroxymelatonin sulfate excretion of Swiss railway workers. J. Pineal Res. 21: 91–100.
- Pioli, C, M. C. Caroleo, G. Nistico, G. Doria (1993) Melatonin increases antigen presentation and amplifies specific and non-specific signals for T-cell proliferation. Int. J. Immunopharmac. 15: 463–468.
- Prato, F. S., K. P. Ossenkopp, M. Kavaliers, P. Uksik, R. L. Nicholson, D. Drost, E. A. Sestini (1989) Effects of exposure to magnetic resonance imaging on nocturnal serum melatonin and other hormone levels in adult males: Preliminary findings. J. Bioelectricity 7: 169–180.
- Puntoni, R., M. Vercelli, F. Merlo, F. Valerio, L. Santi (1979) Mortality among shipyard workers in Genoa, Italy. Ann. N. Y. Acad. Sci. 330: 353–377.
- Quay, W. B. (1974) Pineal Chemistry In Cellular and Physiological Mechanisms. Charles C. Thomas, Springfield , IL , pp. 1–430.
- Reiter, R. J. (1991) Pineal gland: Interface between the photoperiodic environment and the endocrine system. Trend. Endocrinol. Metab. 2: 13–19.
- Reiter, R. J., L. E. Anderson, R. L. Buschbom, B. W. Wilson (1988) Reduction of the nocturnal rise in pineal melatonin levels in rats exposed to 60-Hz electric fields in utero and for 23 days after birth. Life Sci. 42: 2203–2206.
- Reiter, R. J., D. X. Tan, B. Poeggeler, A. Menendez-Pelaez, L. D. Chen, S. Saarela (1994) Melatonin as a free radical scavenger: Implications for aging and age-related diseases. Ann. N. Y. Acad. Sci. 719: 1–12.
- Reiter, R., L. TangJ. J. Garcia, A. Munoz-Hoyos (1997a) Pharmacological actions of melatonin in oxygen radical pathophysiology. Life Sci. 60: 2255–2271.
- Reiter, R. J., R. C. Carneiro, C. S. Oh (1997b) Melatonin in relation to cellular antioxidative defense mechanisms. Horm. Metab. Res. 29: 363–372.
- Reppert, S. M., C. Godson, C. D. Mahle, D. R. Weaver, S. A. Slaugenhaupt, J. F. Gusella (1995) Molecular characterization of a second melatonin receptor expressed in human retina and brain: The Mellb melatonin receptor. Proc. Natl. Acad. Sci. USA 92: 8734–8738.
- Reuss, S., J. Olcese (1986) Magnetic field effects on the rat pineal gland: Role of retinal activation by light. Neurosci. Lett. 64: 97–101.
- Reuss, S., P. Semm (1987) Effects of an earth strength magnetic field on pineal melatonin synthesis in pigeons. Naturwis-senschaften 74: 38–39.
- Reuss, S., P. Semm, L. Vollrath (1983) Different types of magnetically sensitive cells in the rat pineal gland. Neurosci. Lett. 40: 23–26.
- Richardson, B. A., K. Yaga, R. J. Reiter, D. J. Morton (1992) Pulsed static magnetic field effects on in vitro pineal indoleamine metabolism. Biochim. Biophys. Acta 1137: 59–64.
- Richardson, B. A., K. Yaga, R. J. Reiter, P. Hoover (1993) Suppression of nocturnal pineal N-acetyltransferase activity and melatonin content by inverted magnetic fields and induced eddy currents. Int. J. Neurosci. 69: 149–155.
- Rogers, W. R., R. J. Reiter, H. D. Smith, L. Barlow-Walden (1995a) Rapid onset/offset, variably scheduled 60 Hz electric and magnetic field exposure reduces nocturnal serum melatonin concentration in nonhuman primates. Bioelectromagnetics Suppl. 3: 119–122.
- Rogers, W. R., R. J. Reiter, L. Barlow-Walden, H. D. Smith, J. L. Orr (1995b) Regularly scheduled, day-time, slow-onset 60 Hz electric and magnetic field exposure does not depress serum melatonin concentration in nonhuman primates. Bioelectromagnetics Suppl. 3: 111–118.
10.1002/bem.2250160711 Google Scholar
- Rosenbaum, P., J. Vena, M. Zielezny, A. Michalek (1994) Occupational exposures associated with male breast cancer. Am. J. Epidemiol. 139: 30–36.
- Rudolph, K., A. Wirz-Justice, K. Krauchli, H. Feer (1988) Static magnetic fields decrease nocturnal pineal cAMP in the rat. Brain Res. 446: 159–160.
- Sanchez-Barcelo, E. J., M. D. Mediavilla, H. A. Tucker (1990) Influence of melatonin on mammary gland growth: In vivo and in vitro studies. Proc. Soc. Exp. Biol. Med. 194: 103–107.
- Savitz, D. A., D. P. Loomis (1995) Magnetic field exposure in relation to leukemia and brain cancer mortality among electric utility workers. Am. J. Epidemiol. 141: 123–134.
- Schiffman, J. S., H. M. Lasch, M. D. Rollag, A. E. Flanders, G. C. Brainard, D. L. BuRK (1994) Effect of magnetic resonance imaging on the normal human pineal body: Measurement of plasma melatonin levels. J Magn Reson Imaging 4: 7–11.
- Schneider, T., H. P. Thalau, P. Semm (1994) Effects of light of different earth-strength magnetic fields on the nocturnal melatonin concentration in a migratory bird. Neurosci. Lett. 168: 73–75.
- Schreiber, G. H., G. M. Swaen, J. M. Meijers, J. J. Slagen, F. Sturmans (1993) Cancer mortality and residence near electricity transmission equipment: A retrospective cohort study. Int. J. Epidemiol. 22: 9–15.
- Selmaoui, B., Y. Touitou (1995) Sinusoidal 50-Hz magnetic fields depress rat pineal NAT activity and serum melatonin. Role of duration and intensity of exposure. Life Sci. 57: 1351–1358.
- Selmaoui, B., J. Lambrozo, Y. Touitou (1996) Magnetic fields and pineal function in humans: Evaluation of nocturnal acute exposure to extremely low frequency magnetic fields on serum melatonin and urinary 6-sulfatoxymelatonin circadian rhythms. Life Sci. 58: 1539–1549.
- Semm, P. (1983) Neurobiological investigations on the magnetic sensitivity of the pineal gland in rodents and pigeons. Comp. Biochem. Physiol. [A] 76A: 683–689.
- Semm, P., T. Schneider, L. Vollrath (1980) Effects of an earth-strength magnetic field and electrical activity of pineal cells. Nature 288: 607–608.
- Seshadri, R., A. Subramanian, L. Kothari (1992) Effect of neonatal pineal ablation on estradiol receptors in mammary glands of rats housed under varying photoperiods. Ind. J. Exp. Biol. 30: 162–164.
- Shah, P. N., M. C. Mhatre, L. S. Kothari (1984) Effect of melatonin on mammary carcinogenesis in intact and pinealec-tomized rats in varying photoperiods. Cancer Res. 44: 3403–3407.
- Shellard, S. A., R. D. Whelan, B. T. Hill (1989) Growth inhibitory and cytotoxic effects of melatonin and its metabolites on human tumour cell lines in vitro. Br. J. Cancer 60: 288–290.
- Skene, D. J., C. J. Bojkowski, J. E. Currie, J. Wright, P. S. Boulter, J. Arendt (1990) 6-sulphatoxymelatonin production in breast cancer patients. J. Pineal Res. 8: 269–276.
- Soule, H. D., J. Vazguez, A. Long, S. Albert, M. Brennan (1973) A human cell line from a pleural effusion derived from a breast carcinoma. J. Natl. Cancer Inst. 51: 1409–1416.
- Spinelli, J. J., P. R. Band, L. M. Svirchev, R. P. Gallagher (1991) Mortality and cancer incidence in aluminum reduction plant workers. J. Occup. Med. 33: 1150–1155.
- Stehle, J., S. Reuss, H. Schroder, M. Herschel, L. Vollrath (1988) Magnetic field effects on pineal N-acetyl-transferase activity and melatonin content in the gerbil — role of pigmentation and sex. Physiol. Behav. 44: 91–94.
- Stenlund, C, B. Floderus (1997) Occupational exposure to magnetic fields in relation to male breast cancer and testicular cancer: A Swedish case-control study. Cancer Causes Control 8: 184–191.
- Stevens, R. G. (1987) Electric power use and breast cancer: A hypothesis. Am. J. Epidemiol. 125: 556–561.
- Stevens, R. G. (1995) Risk of premenopausal breast cancer and use of electric blankets (letter). Am. J. Epidemiol. 142: 446.
- Stevens, R. G., S. Davis (1996) The melatonin hypothesis: Electric power and breast cancer. Environ. Health Perspect. 104: 135–140.
- Stevens, R. G., S. Davis, D. B. Thomas, L. E. Anderson, B. W. Wilson (1992) Electric power, pineal function, and the risk of breast cancer. FASEB J. 6: 853–860.
- R. G. Stevens, B. W. Wilson. L. E. Anderson, eds. (1997) The Melatonin Hypothesis: Breast Cancer and Use of Electric Power. Battelle Press, Columbus , OH , pp. 1–760.
- Subramanian, A., L. Kothari (1991a) Suppressive effect by melatonin on different phases of 9, 10-dimethyl-1, 2-benzan-thracene (DMBA)-induced rat mammary gland carcinogenesis. Anticancer Drugs 2: 297–303.
- Subramanian, A., L. Kothari (1991b) Melatonin, a suppressor of spontaneous murine mammary tumors. J. Pineal Res. 10: 136–140.
- Tamarkin, L., M. Cohen, D. Roselle, C. Reichert, M. Lippman, B. Chabner (1981) Melatonin inhibition and pinealectomy enhancement of 7, 12-dimethyl-benz[a]anthracene-induced mammary tumors in the rat. Cancer Res. 41: 4432–4436.
- Tamarkin, L., C. J. Baird, O. F. X. Almeida (1985) Melatonin: A coordinating signal for mammalian reproduction. Science 227: 714–720.
- Tan, D. X., B. Poeggeler, R. J. Reiter, L. D. Chen. S. Chen, L. C. Manchester, L. R. Barlow-Walden (1993) The pineal hormone melatonin inhibits DNA-adduct formation induced by the chemical carcinogen safrole in vivo. Cancer Lett. 70: 65–71.
- Theriault, G., M. Goldberg, A. B. Miller, B. Armstrong, P. Guenel, J. Deadman, E. Imbernon, T. To, A. Chevalier, D. Cyr, C. Wall (1994) Cancer risks associated with occupational exposure to magnetic fields among electric workers in Ontario and Quebec, Canada, and France: 1970–1989. Am. J. Epidemiol. 139: 550–572.
- Tornqvist, S., S. Norrell, A. Ahlbom, B. Knave (1986) Cancer in the electric power industry. Br. J. Ind. Med. 43: 212–213.
- Truong, H., J. C. Smith, S. M. Yellon (1996) Photoperiod control of the melatonin rhythm and reproductive maturation in the juvenile Djungarian hamster -60-Hz magnetic field exposure effects. Biol. Reprod. 55: 455–460.
- Truong, H., S. M. Yellon (1997) Effect of various acute 60 Hz magnetic field exposures on the nocturnal melatonin rise in the adult Djungarian hamster. J. Pineal Res. 22: 177–183.
- Tynes, T., A. Andersen, F. Langmark (1992) Incidence of cancer in Norwegian workers potentially exposed to electromagnetic fields. Am. J. Epidemiol. 136: 81–88.
- Tynes, T., J. Reitan, A. Andersen (1994) Incidence of cancer among workers in Norwegian hydroelectric power companies. Scan. J. Work Environ. Health 20: 339–344.
- Tynes, T., M. Hannevik, A. Andersen, A. I. Vistnes, T. Haldorsen (1996) Incidence of breast cancer in Norwegian female radio and telegraph operators. Cancer Causes Control 7: 197–204.
- Ubeda, A., M. A. Trillo, D. E. House, C. F. Blackman (1995) Melatonin enhances junctional transfer in normal C3H/10T1/2 cells. Cancer Lett. 91: 241–245.
- Vagero, D., R. Olin (1983) Incidence of cancer in the electronics industry: Using the new Swedish Cancer Environment Registry as a screening instrument. Br. J. Ind. Med. 40: 188–192.
- Vagero, D., A. Ahlbom, R. Olin, S. Sahlsten (1985) Cancer morbidity among workers in the telecommunications industry. Br. J. Ind. Med. 42: 191–195.
- Vena, J. E., S. Graham, R. Hellman, M. Swanson, J. Brasure (1991) Use of electric blankets and risk of post-menopausal breast cancer. Am. J. Epidemiol. 134: 180–185.
- Vena, J. E., J. L. Freudenheim, J. R. Marshall, R. Laugh-Lin, M. Swanson, S. Graham (1994) Risk of premenopausal breast cancer and use of electric blankets. Am. J. Epidemiol. 140: 974–979.
- Vena, I. E., J. R. Marshall, J. L. Freudenheim, M. Swan-Son, S. Graham (1995) Risk of premenopausal breast cancer and use of electric blankets (letter). Am. J. Epidemiol. 142: 446–447.
- Verkasalo, P. K., E. Pukkala, J. Kaprio, K. V. Heikkilä, M. Koskenvuo (1996) Magnetic fields of high voltage power lines and risk of cancer in Finnish adults: Nationwide cohort study. Br. Med. J. 313: 11–15.
- Vollrath, L. (1981) The Pineal Organ. Springer-Verlag, Berlin , pp. 1–665.
10.1007/978-3-642-81525-6_1 Google Scholar
- Waldhauser, F., G. Weiszenbacher, E. Tatzer, B. Gisinger, M. Waldhauser. M. Schemper, H. Frisch (1988) Alterations in nocturnal serum melatonin levels in humans with growth and aging. J. Clin. Endocrinol. Metab. 66: 648–652.
- Wehr, T. A., D. E. Moul, G. Barbato, H. A. Giesen, J. A. Seidel, C. Barker, C. Bender (1993) Conservation of photoperiod-responsive mechanisms in humans. Am. J. Physiol. 265: R846–R857.
- Welker, H. A., P. Semm, R. P. Willig, J. C. Commentz, W. Wiltschko, L. Vollrath (1983) Effects of an artificial magnetic field on serotonin N-acetyltransferase activity and melatonin content in the rat pineal gland. Exp. Brain Res. 50: 426–432.
- Wertheimer, N., E. Leeper (1982) Adult cancer related to electrical wires near the home. Int. J. Epidemiol. 11: 345–355.
- Wertheimer, N., E. Leeper (1987) Magnetic field exposure related to cancer subtypes. Ann. N. Y. Acad. Sci. 502: 43–54.
- L. Wetterberg, ed. (1993) Light and Biological Rhythms in Man. Pergamon Press, Stockholm , pp. 1–448.
- Wilson, B. W., L. E. Anderson, D. I. Hilton, R. D. Phillips (1981) Chronic exposure to 60-Hz electric fields: Effects on pineal function in the rat. Bioelectromagnetics 2: 371–380.
- Wilson, B. W., L. E. Anderson, D. I. Hilton, R. D. Phillips (1983) Chronic exposure to 60-Hz electric fields: effects on pineal function in the rat [erratum]. Bioelectromagnetics 4: 293.
- Wilson, B. W., E. K. Chess, L. E. Anderson (1986) 60-Hz electric-field effects on pineal melatonin rhythms: Time course for onset and recovery. Bioelectromagnetics 7: 239–242.
- Wilson, B. W., C. W. Wright, J. E. Morris, R. L. Buschbom, D. P. Brown, D. L. Miller, R. Sommers-Flannigan, L. E. Anderson (1990) Evidence for an effect of ELF electromagnetic fields on human pineal gland function. J. Pineal Res. 9: 259–269.
- Wilson, S. T., D. E. Blask, A. M. Lemus-Wilson (1992) Melatonin augments the sensitivity of MCF-7 human breast cancer cells to tamoxifen in vitro. J. Clin. Endocrinol. Metab. 75: 669–670.
- Wolff, M. S., G. W. Collman, J. C. Barrett, J. Huff (1996) Breast cancer and environmental risk factors: Epidemiological and experimental findings. Annu. Rev. Pharmacol. Toxicol. 36: 573–596.
- Yaga, K., R. J. Reiter, L. C. Manchester, H. Nieves. J. H. Sun, L. D. Chen (1993) Pineal sensitivity to pulsed static magnetic field changes during the photoperiod. Brain Res. Bull. 30: 153–156.
- Yellon, S. M. (1994) Acute 60 Hz magnetic field exposure effects on the melatonin rhythm in the pineal gland and circulation of the adult Djungarian hamster. J. Pineal Res. 16: 136–144.
- Yellon, S. M. (1996) 60-Hz magnetic field exposure effects on the melatonin rhythm and photoperiod control of reproduction. Am. J. Physiol. 270: E816–E821.