Do magnetic fields cause increased risk of childhood leukemia via melatonin disruption?

Epidemiological studies have reported associations between exposure to power frequency magnetic fields and increased risk of certain cancer and noncancer illnesses. For childhood leukemia, a doubling of risk has been associated with exposures above 0.3/0.4 microT. Here, we propose that the melatonin hypothesis, in which power frequency magnetic fields suppress the nocturnal production of melatonin in the pineal gland, accounts for the observed increased risk of childhood leukemia. Such melatonin disruption has been shown in animals, especially with exposure to electric and/or rapid on/off magnetic fields. Equivocal evidence has been obtained from controlled laboratory magnetic field exposures of volunteers, although the exposure conditions are generally atypical of neighborhood exposures. In contrast, support for the hypothesis is found in the body of studies showing magnetic field disruption of melatonin in human populations chronically exposed to both electric and magnetic fields associated with electricity distribution. Further support comes from the observation that melatonin is highly protective of oxidative damage to the human haemopoietic system. Aspects of the hypothesis are amenable to further investigation.

[1]  Vijayalaxmi,et al.  Melatonin and protection from whole-body irradiation: survival studies in mice. , 1999, Mutation research.

[2]  E. Lynge.  Risk of breast cancer is also increased among Danish female airline cabin attendants , 1996, BMJ.

[3]  R. Foster,et al.  Regulation of the mammalian pineal by non-rod, non-cone, ocular photoreceptors. , 1999, Science.

[4]  T. Lyon.  MORTALITY from cancer. , 1894, Cancer bulletin.

[5]  A. Swerdlow.  Shift work and breast cancer : a critical review of the epidemiological evidence , 2003 .

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

[7]  E. Ainsbury,et al.  An investigation into the vector ellipticity of extremely low frequency magnetic fields from appliances in UK homes , 2005, Physics in medicine and biology.

[8]  Maria Blettner,et al.  Mortality from cancer and other causes among airline cabin attendants in Germany, 1960-1997. , 2002, American journal of epidemiology.

[9]  A W Wood,et al.  Changes in human plasma melatonin profiles in response to 50 Hz magnetic field exposure , 1998, Journal of pineal research.

[10]  Russell G Foster,et al.  Non-rod, non-cone photoreception in the vertebrates , 2002, Progress in Retinal and Eye Research.

[11]  M. Raybourn.  The effects of direct-current magnetic fields on turtle retinas in vitro. , 1983, Science.

[12]  G. Warman,et al.  Acute exposure to circularly polarized 50-Hz magnetic fields of 200-300 microT does not affect the pattern of melatonin secretion in young men. , 2003, The Journal of clinical endocrinology and metabolism.

[13]  M. Ishido,et al.  Magnetic fields (MF) of 50 Hz at 1.2 microT as well as 100 microT cause uncoupling of inhibitory pathways of adenylyl cyclase mediated by melatonin 1a receptor in MF-sensitive MCF-7 cells. , 2001, Carcinogenesis.

[14]  A. Auvinen,et al.  Incidence of cancer among Finnish airline cabin attendants, 1967-92 , 1995, BMJ.

[15]  B Claustrat,et al.  Daytime 50 Hz magnetic field exposure and plasma melatonin and urinary 6‐sulfatoxymelatonin concentration profiles in humans , 2001, Journal of pineal research.

[16]  H. Nitta,et al.  Acute exposure to 50 Hz magnetic fields with harmonics and transient components: Lack of effects on nighttime hormonal secretion in men , 2003, Bioelectromagnetics.

[17]  R D Phillips,et al.  Chronic exposure to 60-Hz electric fields: effects on pineal function in the rat. , 1981, Bioelectromagnetics.

[18]  Thorsten Ritz,et al.  Resonance effects indicate a radical-pair mechanism for avian magnetic compass , 2004, Nature.

[19]  L. E. Anderson,et al.  Effects of 60 Hz magnetic field exposure on the pineal and hypothalamic-pituitary-gonadal axis in the Siberian hamster (Phodopus sungorus). , 1999, Bioelectromagnetics.

[20]  L. E. Anderson,et al.  The melatonin hypothesis : breast cancer and use of electric power , 1997 .

[21]  Josep M. Guerrero,et al.  Evidence of melatonin synthesis by human lymphocytes and its physiological significance: possible role as intracrine, autocrine, and/or paracrine substance , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[22]  J. Reif,et al.  Nocturnal excretion of a urinary melatonin metabolite among electric utility workers. , 1998, Scandinavian journal of work, environment & health.

[23]  M. Biel,et al.  Melanopsin and rod–cone photoreceptive systems account for all major accessory visual functions in mice , 2003, Nature.

[24]  R. Stevens,et al.  Electric power use and breast cancer: a hypothesis. , 1987, American journal of epidemiology.

[25]  K. Jaffa,et al.  Pooled analysis of magnetic fields, wire codes, and childhood leukemia. , 2001, Epidemiology.

[26]  D. Acuña-Castroviejo,et al.  Free Radical‐Mediated Molecular Damage , 2001, Annals of the New York Academy of Sciences.

[27]  L. Wetterberg,et al.  Geomagnetic activity influences the melatonin secretion at latitude 70 degrees N. , 2001, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[28]  S. Yellon,et al.  Acute 60 Hz magnetic field exposure effects on the melatonin rhythm in the pineal gland and circulation of the adult Djungarian hamster , 1994, Journal of pineal research.

[29]  K. Manton,et al.  Effect of exposure to light‐at‐night on life span and spontaneous carcinogenesis in female CBA mice , 2004, International journal of cancer.

[30]  S. Weintraub,et al.  Identification of highly elevated levels of melatonin in bone marrow: its origin and significance. , 1999, Biochimica et biophysica acta.

[31]  J. Stockman.  Geographical Patterns and Time Trends of Cancer Incidence and Survival Among Children and Adolescents in Europe Since the 1970s (the ACCIS Project): An Epidemiological Study , 2006 .

[32]  E. Steliarova-Foucher,et al.  Geographical patterns and time trends of cancer incidence and survival among children and adolescents in Europe since the 1970s (the ACCIS project): an epidemiological study , 2004, The Lancet.

[33]  Growth Factors,et al.  Minireview , 1999 .

[34]  H. Sutton.  AN EPIDEMIOLOGICAL STUDY , 1937 .

[35]  Y. Touitou,et al.  Reproducibility of the circadian rhythms of serum cortisol and melatonin in healthy subjects: a study of three different 24-h cycles over six weeks. , 2003, Life sciences.

[36]  O.P. Gandhi,et al.  Calculation of electric fields and currents induced in a millimeter-resolution human model at 60 Hz using the FDTD method with a novel time-to-frequency-domain conversion , 1996, IEEE Antennas and Propagation Society International Symposium. 1996 Digest.

[37]  B. Griefahn,et al.  Melatonin production during childhood and adolescence: a longitudinal study on the excretion of urinary 6‐hydroxymelatonin sulfate , 2003, Journal of pineal research.

[38]  L. E. Anderson,et al.  Nocturnal 6‐hydroxymelatonin sulfate excretion in female workers exposed to magnetic fields , 2000, Journal of pineal research.

[39]  Vijayalaxmi,et al.  Melatonin: possible mechanisms involved in its 'radioprotective' effect. , 1998, Mutation research.

[40]  R. Foster,et al.  Regulation of mammalian circadian behavior by non-rod, non-cone, ocular photoreceptors. , 1999, Science.

[41]  M. Lippman,et al.  ROLE OF PINEAL GLAND IN ÆTIOLOGY AND TREATMENT OF BREAST CANCER , 1978, The Lancet.

[42]  W. Löscher,et al.  Magnetic Fields and Breast Cancer: Experimental in Vivo Studies on the Melatonin Hypothesis , 1999 .

[43]  Robert J. Lucas,et al.  Characterization of an ocular photopigment capable of driving pupillary constriction in mice , 2001, Nature Neuroscience.

[44]  W. Wiltschko,et al.  Effects of an artificial magnetic field on serotonin N-acetyltransferase activity and melatonin content of the rat pineal gland , 2004, Experimental Brain Research.

[45]  P. Natali,et al.  Targeting endothelin axis in cancer. , 2004, Cancer treatment and research.

[46]  R. Stevens,et al.  The melatonin hypothesis: electric power and breast cancer. , 1996, Environmental health perspectives.

[47]  Johnni Hansen,et al.  Increased Breast Cancer Risk among Women Who Work Predominantly at Night , 2001, Epidemiology.

[48]  Y. Touitou,et al.  Endocrine functions in young men exposed for one night to a 50-Hz magnetic field. A circadian study of pituitary, thyroid and adrenocortical hormones. , 1997, Life sciences.

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

[50]  A. Wakatsuki,et al.  Melatonin increases activities of glutathione peroxidase and superoxide dismutase in fetal rat brain , 2000, Journal of pineal research.

[51]  L. E. Anderson,et al.  Evidence for an Effect of ELF Electromagnetic Fields on Human Pineal Gland Function , 1990, Journal of pineal research.

[52]  R Ohtsuka,et al.  Chronic exposure to ELF magnetic fields during night sleep with electric sheet: effects on diurnal melatonin rhythms in men. , 2001, Bioelectromagnetics.

[53]  L. E. Anderson,et al.  60-Hz electric-field effects on pineal melatonin rhythms: time course for onset and recovery. , 1986, Bioelectromagnetics.

[54]  M. Bourdages,et al.  Effects of electric and magnetic fields from high-power lines on female urinary excretion of 6-sulfatoxymelatonin. , 2001, American journal of epidemiology.

[55]  R. Reiter,et al.  Pineal melatonin: cell biology of its synthesis and of its physiological interactions. , 1991, Endocrine reviews.

[56]  Rate of occurrence of transient magnetic field events in U.S. residences. , 2000, Bioelectromagnetics.

[57]  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.

[58]  W T Kaune,et al.  Residential magnetic fields, light-at-night, and nocturnal urinary 6-sulfatoxymelatonin concentration in women. , 2001, American journal of epidemiology.

[59]  J. Reif,et al.  Melatonin metabolite levels in workers exposed to 60-Hz magnetic fields: work in substations and with 3-phase conductors. , 2000, Journal of occupational and environmental medicine.

[60]  R Kavet,et al.  Inconsistent suppression of nocturnal pineal melatonin synthesis and serum melatonin levels in rats exposed to pulsed DC magnetic fields. , 1998, Bioelectromagnetics.

[61]  R. Hahn,et al.  Profound bilateral blindness and the incidence of breast cancer. , 1991, Epidemiology.

[62]  J. Reif,et al.  Reduced excretion of a melatonin metabolite in workers exposed to 60 Hz magnetic fields. , 1999, American journal of epidemiology.

[63]  D. Cavallo,et al.  Effects of 50 Hz magnetic fields on mouse spermatogenesis monitored by flow cytometric analysis. , 1995, Bioelectromagnetics.

[64]  Eberhard Gwinner.  Rhythms of life - The biological clocks that control the daily lives of every living thing , 2004 .

[65]  T. Erren,et al.  A meta-analysis of epidemiologic studies of electric and magnetic fields and breast cancer in women and men. , 2001, Bioelectromagnetics.

[66]  W R Rogers,et al.  Rapid-onset/offset, variably scheduled 60 Hz electric and magnetic field exposure reduces nocturnal serum melatonin concentration in nonhuman primates. , 1995, Bioelectromagnetics.

[67]  C E Minder,et al.  Effects of exposure to 16.7 Hz magnetic fields on urinary 6‐hydroxymelatonin sulfate excretion of Swiss railway workers , 1996, Journal of pineal research.

[68]  R. Stevens,et al.  Inverse association between breast cancer incidence and degree of visual impairment in Finland , 1999, British Journal of Cancer.

[69]  M Hietanen,et al.  Non-ionizing Radiation, Part 1: Static and Extremely Low-frequency (elf) Electric and Magnetic Fields , 2002 .

[70]  M R Cook,et al.  Human melatonin during continuous magnetic field exposure. , 1997, Bioelectromagnetics.

[71]  S. Yellon,et al.  Melatonin Rhythm Onset in the Adult Siberian Hamster: Influence of Photoperiod But Not 60-Hz Magnetic Field Exposure on Melatonin Content in the Pineal Gland and in Circulation , 1998, Journal of biological rhythms.

[72]  C. Gentile,et al.  The chemistry of melatonin's interaction with reactive species , 2003, Journal of pineal research.

[73]  A. Wakatsuki,et al.  Effect of ischemia-reperfusion on xanthine oxidase activity in fetal rat brain capillaries. , 1999, American journal of obstetrics and gynecology.

[74]  Tore Tynes,et al.  Residential and occupational exposures to 50-Hz magnetic fields and breast cancer in women: a population-based study. , 2004, American journal of epidemiology.

[75]  M Feychting,et al.  A pooled analysis of magnetic fields and childhood leukaemia , 2000, British Journal of Cancer.

[76]  Vijayalaxmi,et al.  Melatonin and radioprotection from genetic damage: in vivo/in vitro studies with human volunteers. , 1996, Mutation research.

[77]  Robert J. Lucas,et al.  Calcium Imaging Reveals a Network of Intrinsically Light-Sensitive Inner-Retinal Neurons , 2003, Current Biology.

[78]  Y. Touitou,et al.  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. , 1996, Life sciences.

[79]  N. Zisapel,et al.  Melatonin production in infants. , 2002, Pediatric neurology.

[80]  J. Hansen,et al.  Light at night, shiftwork, and breast cancer risk. , 2001, Journal of the National Cancer Institute.

[81]  A. Lerchl,et al.  Direct suppressive effects of weak magnetic fields (50 Hz and 162/3 Hz) on melatonin synthesis in the pineal gland of Djungarian hamsters (Phodopus sungorus) , 2000, Journal of pineal research.

[82]  P. Cerutti,et al.  The role of the cellular antioxidant defense in oxidant carcinogenesis. , 1994, Environmental health perspectives.

[83]  P. Riley.  THE MELATONIN HYPOTHESIS: BREAST CANCER AND USE OF ELECTRIC POWER , 1998 .

[84]  A. Wakatsuki,et al.  Melatonin protects against ischemia/reperfusion‐induced oxidative damage to mitochondria in fetal rat brain , 2001, Journal of pineal research.

[85]  A. Wakatsuki,et al.  Maternal‐fetal transfer of melatonin in pregnant women near term , 1998, Journal of pineal research.

[86]  G. Maestroni,et al.  Evidence for melatonin synthesis in mouse and human bone marrow cells , 2000, Journal of pineal research.

[87]  J. Reif,et al.  Melatonin metabolite excretion among cellular telephone users , 2002, International journal of radiation biology.

[88]  R. Reiter,et al.  Pharmacological actions of melatonin in oxygen radical pathophysiology. , 1997, Life sciences.

[89]  P. Semm,et al.  Effects of an Earth-strength magnetic field on electrical activity of pineal cells , 1980, Nature.

[90]  R. Reiter,et al.  Antioxidant strategies in protection against neurodegenerative disorders , 2003 .

[91]  R. Kronauer,et al.  Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression , 2000, The Journal of physiology.

[92]  A. Wakatsuki,et al.  Oxidative Damage in Fetal Rat Brain Induced by Ischemia and Subsequent Reperfusion , 1999, Neonatology.

[93]  B. Griefahn,et al.  Experiments on the effects of a continuous 16.7 Hz magnetic field on melatonin secretion, core body temperature, and heart rates in humans , 2001, Bioelectromagnetics.

[94]  Josep M. Guerrero,et al.  Melatonin inhibits telomerase activity in the MCF‐7 tumor cell line both in vivo and in vitro , 2003, Journal of pineal research.

[95]  Jacques Lambrozo,et al.  Magnetic fields and the melatonin hypothesis: a study of workers chronically exposed to 50-Hz magnetic fields. , 2003, American journal of physiology. Regulatory, integrative and comparative physiology.

[96]  Vanesa Martín,et al.  Regulation of antioxidant enzymes: a significant role for melatonin , 2004, Journal of pineal research.

[97]  R. Reiter.  Melatonin in the context of the reported bioeffects of environmental electromagnetic fields , 1998 .

[98]  Cantab Ma.  John Crighton Bramwell. , 1976 .

[99]  S. Reuss,et al.  Evidence for the involvement of the visual system in mediating magnetic field effects on pineal melatonin synthesis in the rat , 1985, Brain Research.

[100]  N. Sugino,et al.  Changes of serum melatonin level and its relationship to feto‐placental unit during pregnancy , 2001, Journal of Pineal Research.

[101]  M. Lippman,et al.  PINEAL GLAND AND BREAST CANCER , 1978, The Lancet.

[102]  H. Ra.  Does blindness protect against cancers , 1998 .

[103]  L. E. Anderson,et al.  Effects of 50- or 60-hertz, 100 microT magnetic field exposure in the DMBA mammary cancer model in Sprague-Dawley rats: possible explanations for different results from two laboratories. , 2000, Environmental health perspectives.

[104]  Wolfgang Löscher,et al.  Significant Differences in the Effects of Magnetic Field Exposure on 7,12-Dimethylbenz(a)anthracene-Induced Mammary Carcinogenesis in Two Substrains of Sprague-Dawley Rats , 2004, Cancer Research.

[105]  M. Greaves.  Science, medicine, and the future: Childhood leukaemia , 2002 .

[106]  M Feychting,et al.  Reduced Cancer Incidence among the Blind , 1998, Epidemiology.

[107]  H D Cohen,et al.  Nocturnal melatonin levels in human volunteers exposed to intermittent 60 Hz magnetic fields. , 1996, Bioelectromagnetics.

[108]  K. Yau,et al.  Diminished Pupillary Light Reflex at High Irradiances in Melanopsin-Knockout Mice , 2003, Science.

[109]  Charles Graham,et al.  Multi‐night exposure to 60 Hz magnetic fields: Effects on melatonin and its enzymatic metabolite , 2000, Journal of pineal research.

[110]  S. Reuss,et al.  Different types of magnetically sensitive cells in the rat pineal gland , 1983, Neuroscience Letters.

[111]  J. Reif,et al.  Geomagnetic disturbances are associated with reduced nocturnal excretion of a melatonin metabolite in humans , 1999, Neuroscience Letters.