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Berson, David M. (2007): Phototransduction in ganglion-cell photoreceptors. In: Pflügers Archiv : European
j
ournal ofphy si
ol
ogy,J g.454,H.5,S.849– 855.Onl i
never fügbarunt erdoi :
10.1007/ s00424- 007- 0242- 2.
Abstract A third class of photoreceptors has recently been identified in the mammalian
retina. They are a rare cell type within the class of ganglion cells, which are the
output cells of the retina. These intrinsically photosensitive retinal ganglion cells
support a variety of physiological responses to daylight, including synchronization of
circadian rhythms, modulation of melatonin release, and regulation of pupil size.
The goal of this review is to summarize what is currently known concerning the
cellular and biochemical basis of phototransduction in these cells. I summarize the
overwhelming evidence that melanopsin serves as the photopigment in these cells
and review the emerging evidence that the downstream signaling cascade,
including the light-gated channel, might resemble those found in rhabdomeric
invertebrate photoreceptors.
Schlagwörter Animals; Humans; Light; Light Signal Transductionphysiology; Photoreceptor Cells,
Invertebrateanatomy & histologyphysiology; Photoreceptor Cells,
Vertebratecytologyphysiologyradiation effects; Retinal Ganglion
Cellscytologyphysiologyradiation effects; Retinal Pigmentsmetabolismradiation
effects; Rod Opsinsmetabolismradiation effects; Visual Pathwaysanatomy &
histologyphysiology

Brainard, G. C. (1979): Pineal research: the decade of transformation. In: Journal of neural transmission.
Supplement um,H.13,S.3– 10.
Abstract In a little more than a decade (1954--1965), the pineal gland was demonstrated to
be an active neuroendocrine transducer in contrast to a functionless vestige as
earlier supposed. The two major contributions which laid the groundwork for the
development of modern pineal science were Kitay and Altschule's book The Pineal
Gland (1954) and Lerner's isolation and structural work on melatonin (1958). After
Lerner's discovery, biochemists, anatomists, and physiologists determined much
about the structure and function of the pineal gland. In 1965, Wurtman and Axelrod
tied this earlier work together by characterizing the pineal as a neuroendocrine
transducer.
Schlagwörter Animals; History, 20th Century; Melatoninmetabolism; Neurophysiologyhistory;
Pineal Glandanatomy & histologyphysiology; Serotoninmetabolism; United States

Brainard, G. C.; Kavet, R.; Kheifets, L. I. (1999): The relationship between electromagnetic field and light
exposures to melatonin and breast cancer risk: a review of the relevant literature. In: Journal of pineal research,
Jg.26,H.2,S.65– 100.
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
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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.
Schlagwörter Animals; Breast Neoplasmsepidemiologyetiology; Breast Neoplasms,
Maleepidemiologyetiology; Electromagnetic Fieldsadverse effects; Environmental
Exposure; Female; Humans; Light; Male; Melatoninphysiology; Occupational
Exposure

Brainard, G. C.; Matthews, S. A.; Steger, R. W.; Reiter, R. J.; Asch, R. H. (1984): Day:night variations of
melatonin, 5-hydroxyindole acetic acid, serotonin, serotonin N-acetyltransferase, tryptophan, norepinephrine and
dopami nei nther abbitpi
nealgl and.I n:Li f
esc i
enc es,J g.35,H.15,S.1615– 1622.
Abstract Pineal tryptophan, serotonin, serotonin-N-acetyltransferase (NAT), melatonin, 5-
hydroxyindole acetic acid (5HIAA), norepinephrine and dopamine were measured in
5 castrated rabbits each at 11.00, 00.30 and 03.00 hours. The rabbits were housed
in an L:D 14:10 (lights on 07.00 hours). Significant day:night variations were found
in NAT, melatonin, dopamine and norepinephrine. These results were compared to
data concerning rhythms of pineal constituents in other species.
Schlagwörter Acetyltransferasesmetabolism; Animals; Arylamine N-Acetyltransferasemetabolism;
Circadian Rhythm; Dopaminemetabolism; Female; Hydroxyindoleacetic
Acidmetabolism; Male; Melatoninmetabolism; Norepinephrinemetabolism; Pineal
Glandmetabolism; Rabbits; Serotoninmetabolism; Tryptophanmetabolism

Brainard, George C.; Sliney, David; Hanifin, John P.; Glickman, Gena; Byrne, Brenda; Greeson, Jeffrey M. et al.
(2008): Sensitivity of the human circadian system to short-wavelength (420-nm) light. In: Journal of biological
rhyt
hms ,Jg.23,H.5,S.379–386.Onl inev erf
ügbarunt erdoi :10.1177/ 0748730408323089.
Abstract The circadian and neurobehavioral effects of light are primarily mediated by a
retinal ganglion cell photoreceptor in the mammalian eye containing the
photopigment melanopsin. Nine action spectrum studies using rodents, monkeys,
and humans for these responses indicate peak sensitivities in the blue region of the
visible spectrum ranging from 459 to 484 nm, with some disagreement in short-
wavelength sensitivity of the spectrum. The aim of this work was to quantify the
sensitivity of human volunteers to monochromatic 420-nm light for plasma
melatonin suppression. Adult female (n=14) and male (n=12) subjects participated
in 2 studies, each employing a within-subjects design. In a fluence-response study,
subjects (n=8) were tested with 8 light irradiances at 420 nm ranging over a 4-log
unit photon density range of 10(10) to 10(14) photons/cm(2)/sec and 1 dark
exposure control night. In the other study, subjects (n=18) completed an experiment
comparing melatonin suppression with equal photon doses (1.21 x 10(13)
photons/cm(2)/sec) of 420 nm and 460 nm monochromatic light and a dark
exposure control night. The first study demonstrated a clear fluence-response
relationship between 420-nm light and melatonin suppression (p<0.001) with a half-
saturation constant of 2.74 x 10(11) photons/cm(2)/sec. The second study showed
that 460-nm light is significantly stronger than 420-nm light for suppressing
melatonin (p<0.04). Together, the results clarify the visible short-wavelength
sensitivity of the human melatonin suppression action spectrum. This basic
physiological finding may be useful for optimizing lighting for therapeutic and other
applications.
Schlagwörter Adult; Circadian Rhythmradiation effects; Female; Humans; Light; Male;
Melatoninmetabolism; Models, Biological; Neurosecretory Systems; Photons; Pineal
Glandmetabolism; Retinal Ganglion Cellsmetabolism; Vision, Ocular

Brainard, George C.; Sliney, David; Hanifin, John P.; Glickman, Gena; Byrne, Brenda; Greeson, Jeffrey M. et al.
(2008): Sensitivity of the human circadian system to short-wavelength (420-nm) light. In: Journal of biological
rhyt
hms ,Jg.23,H.5,S.379–386.Onl inev er f
ügbarunt erdoi:10. 1177/ 0748730408323089.
Abstract The circadian and neurobehavioral effects of light are primarily mediated by a
retinal ganglion cell photoreceptor in the mammalian eye containing the
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photopigment melanopsin. Nine action spectrum studies using rodents, monkeys,
and humans for these responses indicate peak sensitivities in the blue region of the
visible spectrum ranging from 459 to 484 nm, with some disagreement in short-
wavelength sensitivity of the spectrum. The aim of this work was to quantify the
sensitivity of human volunteers to monochromatic 420-nm light for plasma
melatonin suppression. Adult female (n=14) and male (n=12) subjects participated
in 2 studies, each employing a within-subjects design. In a fluence-response study,
subjects (n=8) were tested with 8 light irradiances at 420 nm ranging over a 4-log
unit photon density range of 10(10) to 10(14) photons/cm(2)/sec and 1 dark
exposure control night. In the other study, subjects (n=18) completed an experiment
comparing melatonin suppression with equal photon doses (1.21 x 10(13)
photons/cm(2)/sec) of 420 nm and 460 nm monochromatic light and a dark
exposure control night. The first study demonstrated a clear fluence-response
relationship between 420-nm light and melatonin suppression (p<0.001) with a half-
saturation constant of 2.74 x 10(11) photons/cm(2)/sec. The second study showed
that 460-nm light is significantly stronger than 420-nm light for suppressing
melatonin (p<0.04). Together, the results clarify the visible short-wavelength
sensitivity of the human melatonin suppression action spectrum. This basic
physiological finding may be useful for optimizing lighting for therapeutic and other
applications.
Schlagwörter Adult; Circadian Rhythmradiation effects; Female; Humans; Light; Male;
Melatoninmetabolism; Models, Biological; Neurosecretory Systems; Photons; Pineal
Glandmetabolism; Retinal Ganglion Cellsmetabolism; Vision, Ocular

Buijs, Ruud M.; Scheer, Frank A.; Kreier, Felix; Yi, Chunxia; Bos, Nico; Goncharuk, Valeri D.; Kalsbeek, Andries
(2006): Organization of circadian functions: interaction with the body. In: Progress in brain research, Jg. 153, S.
341– 360.Onl i
never f
ügbarunt erdoi :
10.1016/ S0079- 6123( 06)53020- 1.
Abstract The hypothalamus integrates information from the brain and the body; this activity is
essential for survival of the individual (adaptation to the environment) and the
species (reproduction). As a result, countless functions are regulated by
neuroendocrine and autonomic hypothalamic processes in concert with the
appropriate behaviour that is mediated by neuronal influences on other brain areas.
In the current chapter attention will be focussed on fundamental hypothalamic
systems that control metabolism, circulation and the immune system. Herein a
system is defined as a physiological and anatomical functional unit, responsible for
the organisation of one of these functions. Interestingly probably because these
systems are essential for survival, their function is highly dependent on each other's
performance and often shares same hypothalamic structures. The functioning of
these systems is strongly influenced by (environmental) factors such as the time of
the day, stress and sensory autonomic feedback and by circulating hormones. In
order to get insight in the mechanisms of hypothalamic integration we have
focussed on the influence of the biological clock; the suprachiasmatic nucleus
(SCN) on processes that are organized by and in the hypothalamus. The SCN
imposes its rhythm onto the body via three different routes of communication: 1.Via
the secretion of hormones; 2. via the parasympathetic and 3.via the sympathetic
autonomous nervous system. The SCN uses separate connections via either the
sympathetic or via the parasympathetic system not only to prepare the body for the
coming change in activity cycle but also to prepare the body and its organs for the
hormones that are associated with such change. Up till now relatively little attention
has been given to the question how peripheral information might be transmitted
back to the SCN. Apart from light and melatonin little is known about other systems
from the periphery that may provide information to the SCN. In this chapter attention
will be paid to e.g. the role of the circumventricular organs in passing info to the
SCN. Herein especially the role of the arcuate nucleus (ARC) will be highlighted.
The ARC is crucial in the maintenance of energy homeostasis as an integrator of
long- and short-term hunger and satiety signals. Receptors for metabolic hormones
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like insulin, leptin and ghrelin allow the ARC to sense information from the periphery
and signal it to the central nervous system. Neuroanatomical tracing studies using
injections of a retrograde and anterograde tracer into the ARC and SCN showed a
reciprocal connection between the ARC and the SCN which is used to transmit
feeding related signals to the SCN. The implications of multiple inputs and outputs
of the SCN to the body will be discussed in relation with metabolic functions.
Schlagwörter Animals; Autonomic Pathwaysphysiology; Biological Clocksphysiology; Circadian
Rhythmphysiology; Endocrine Systemphysiology; Humans;
Hypothalamuscytologyphysiology; Neuronsphysiology; Neuropeptidesmetabolism

Bullough, J.; Rea, M. S.; Stevens, R. G. (1996): Light and magnetic fields in a neonatal intensive care unit. In:
Bioelectromagnet i
cs,J g.17,H.5,S.396–405.Onl i
nev er f
ügbarunt erdoi:10. 1002/(SICI )
1521-
186X(1996)17:5<396::AID-BEM7>3.0.CO;2-Z.
Abstract Effects of light and electromagnetic fields (EMFs) on pineal function could have
implications for long-term risk of breast cancer, reproductive irregularities, or
depression. Health-care workers in a neonatal intensive care unit (NICU) were
interviewed to determine the tasks, work locations, and practices in their work
environment as well as the care provided to the infants. After an initial visit,
methods for measuring illuminance, luminance, and broadband resultant magnetic
fields throughout the NICU were developed. Measurements were made of one
nursery during a daytime (1:00 p.m.) and a night-time (12:30 a.m.) visit.
Measurements relevant to both nurses and premature infants in the NICU were
made. Some measurements could not be completed so as not to interfere with
nurses' duties in the NICU. Illuminances measured during the daytime and
nighttime averaged 184 and 34 lux (lx), respectively, much lower than those
reported in other studies of illuminance in NICUs, with a maximum illuminance of
747 lx. Peak levels may be consistent with those thought to suppress melatonin.
There was a high degree of variability in EMF levels, which exceeded 1,000 mG
close to certain hospital equipment but averaged 1-2 mG at the nurses' workstation.
Fields within incubators exceeded 10 mG.
Schlagwörter Breast Neoplasms; Circadian Rhythm; Depression; Electromagnetic Fields;
Equipment and Supplies, Hospital; Female; Humans; Incubators, Infant; Infant,
Newborn; Infant, Premature; Intensive Care Units, Neonatal; Light; Melatonin;
Neonatal Nursing; Pineal Gland; Reproduction; Risk Factors; Task Performance
and Analysis; Workplace

Bullough, John D.; Bierman, Andrew; Figueiro, Mariana G.; Rea, Mark S. (2008): On melatonin suppression
fr
om polyc hromat icandnar rowbandl i
ght.I n:Chronobi ologyi nter nat
i
onal,Jg.25,H.4,S.653– 656.Onl
i
ne
verfügbar unter doi:10.1080/07420520802247472.
Schlagwörter Circadian Rhythm; Humans; Light; Lightingmethods; Melatoninradiation
effectssecretion; Models, Biological; Rod Opsinsradiation effects

Caplan, L. S.; Schoenfeld, E. R.; O'Leary, E. S.; Leske, M. C. (2000): Breast cancer and electromagnetic fields--
arev i
ew.I n:Annal sofepi demi ology,Jg.10,H.1,S.31–44.
Abstract PURPOSE: Several statements have been issued to the effect that no consistent,
significant link has been demonstrated between cancer and electromagnetic fields
(EMF). However, there continues to be much interest in a possible association with
breast cancer, in part because breast cancer risk is substantially higher in
industrialized countries than in other areas, and electric power generation and
consumption is one of the hallmarks of industrialized societies. In 1987, Stevens
proposed a biological mechanism whereby two products of electric power
generation, EMF and light at night, might contribute to mammary carcinogenesis
through inhibition of melatonin. METHODS: We conducted a comprehensive review
of the epidemiologic literature and hypothesized mechanisms pertaining to EMF
exposure and the risk of breast cancer, in order to assess whether or not there was
evidence to suggest a link between EMF and breast cancer. RESULTS: Some
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occupational epidemiological studies have demonstrated an increased incidence of
breast cancer among mainly male electrical workers. It has been difficult to study
women, as few are employed in these types of occupations. In all, there have been
eleven occupational studies related to breast cancer in women, and statistically
significant risk ratios have been observed: 1.98 for pre-menopausal women in
occupations with high EMF exposure in one study, 2.17 in all women who worked
as telephone installers, repairers, and line workers in another study, and 1.65 for
system analysts/ programmers, 1.40 for telegraph and radio operators, and 1.27 for
telephone operators in a third study. However, six of the studies did not find any
significant effects and two found effects only in subgroups. The results of the eight
studies of residential exposure and four electric blanket studies have been
inconsistent, with most not demonstrating any significant association. However, this
might be attributed, at least to some extent, to difficulties in assessing residential
exposure in these studies, as well as other methodological considerations.
CONCLUSIONS: The biologic plausibility of an association between EMF and
breast cancer, coupled with suggestive data from occupational studies and
unexplained high incidence rates of breast cancer, suggests that further
investigation of this possible association is warranted.
Schlagwörter Breast Neoplasms; Electromagnetic Fields; Environmental Exposure; Female;
Humans; Male; Occupational Diseases; Risk Factors

Cook, M. R.; Graham, C.; Kavet, R.; Stevens, R. G.; Davis, S.; Kheifets, L. (2000): Morning urinary assessment
ofnoctur nalmelatoni
nsecr eti
oni nol derwomen.I n:Jour nalofpi nealres earch,Jg.28,H.1,S.41–47.
Abstract We evaluated the feasibility of using morning urine samples in epidemiological
studies aimed at clarifying the relationship between nocturnal melatonin levels and
breast cancer risk. Initially, a laboratory-based study of 29 women (40- 70 yr old)
was performed to examine the correlation between plasma melatonin levels in
hourly nocturnal blood samples and both melatonin and its major enzymatic
metabolite, 6-hydroxymelatonin-sulfate (6-OHMS) in morning urine samples. In a
companion field study, morning urine samples were collected from 203 healthy
women to assess similarities and differences in laboratory versus field measures.
Taken together, our results indicate: 1) levels of melatonin and of creatinine-
corrected 6-OHMS in the first morning void urine are strongly correlated with total
nocturnal plasma melatonin output (P < 0.001) and also with peak nocturnal
melatonin values (P < 0.001); 2) similar ranges for 6-OHMS were found in the
laboratory and the field; and 3) neither menopausal status nor hormonal
replacement therapy altered 6-OHMS values in morning void urine. The inclusion of
morning urine samples in epidemiological studies of cancer could allow cost-
effective, widespread testing of the role played by melatonin in human health and
disease.
Schlagwörter Adult; Aged; Breast Neoplasms; Circadian Rhythm; Female; Humans; Melatonin;
Middle Aged; Pineal Gland; Radioimmunoassay; Risk Factors

Davis, S.; Kaune, W. T.; Mirick, D. K.; Chen, C.; Stevens, R. G. (2001): Residential magnetic fields, light-at-
night, and nocturnal urinary 6-sulfatoxymelatonin concentration in women. In: American journal of epidemiology,
Jg.154,H.7,S.591– 600.
Abstract Exposure to 60-Hz magnetic fields may increase breast cancer risk by suppressing
the normal nocturnal rise in melatonin. This 1994-1996 Washington State study
investigated whether such exposure was associated with lower nocturnal urinary
concentration of 6-sulfatoxymelatonin in 203 women aged 20-74 years with no
history of breast cancer. Each woman was interviewed and provided data on the
following for a 72-hour period at two different seasons of the year: 1) magnetic field
and ambient light measured every 30 seconds in her bedroom, 2) personal
magnetic field measured at 30-second intervals, and 3) complete nighttime urine
samples on three consecutive nights. Lower nocturnal urinary 6-sulfatoxymelatonin
level was associated with more hours of daylight, older age, higher body mass
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index, current alcohol consumption, and current use of medications classified as
beta blockers, calcium channel blockers, or psychotropics. After adjustment for
these factors, higher bedroom magnetic field level was associated with significantly
lower urinary concentration of 6-sulfatoxymelatonin during the same night, primarily
in women who used these medications and during times of the year with the fewest
hours of darkness. These results suggest that exposure to nighttime residential 60-
Hz magnetic fields can depress the normal nocturnal rise in melatonin.
Schlagwörter Adrenergic beta-Antagonists; Adult; Age Factors; Aged; Alcohol Drinking; Body
Mass Index; Breast Neoplasms; Calcium Channel Blockers; Circadian Rhythm;
Female; Humans; Lighting; Magnetics; Melatonin; Menopause; Middle Aged;
Psychotropic Drugs; Residence Characteristics; Risk Factors; Seasons; Smoking

Davis, S.; Mirick, D. K.; Stevens, R. G. (2001): Night shift work, light at night, and risk of breast cancer. In:
Journal oftheNat ional Canc erI nsti
tut
e,Jg.93,H.20,S.1557–1562.
Abstract BACKGROUND: Exposure to light at night may increase the risk of breast cancer
by suppressing the normal nocturnal production of melatonin by the pineal gland,
which, in turn, could increase the release of estrogen by the ovaries. This study
investigated whether such exposure is associated with an increased risk of breast
cancer in women. METHODS: Case patients (n = 813), aged 20-74 years, were
diagnosed from November 1992 through March 1995; control subjects (n = 793)
were identified by random-digit dialing and were frequency matched according to 5-
year age groups. An in-person interview was used to gather information on sleep
habits and bedroom lighting environment in the 10 years before diagnosis and
lifetime occupational history. Odds ratios (ORs) and 95% confidence intervals (CIs)
were estimated by use of conditional logistic regression, with adjustment for other
potential risk factors. RESULTS: Breast cancer risk was increased among subjects
who frequently did not sleep during the period of the night when melatonin levels
are typically at their highest (OR = 1.14 for each night per week; 95% CI = 1.01 to
1.28). Risk did not increase with interrupted sleep accompanied by turning on a
light. There was an indication of increased risk among subjects with the brightest
bedrooms. Graveyard shiftwork was associated with increased breast cancer risk
(OR = 1.6; 95% CI = 1.0 to 2.5), with a trend of increased risk with increasing years
and with more hours per week of graveyard shiftwork (P =.02, Wald chi-squared
test). CONCLUSION: The results of this study provide evidence that indicators of
exposure to light at night may be associated with the risk of developing breast
cancer.
Schlagwörter Adult; Aged; Breast Neoplasms; Circadian Rhythm; Electromagnetic Fields;
Environmental Exposure; Female; Habits; Humans; Light; Lighting; Melatonin;
Middle Aged; Occupational Exposure; Occupations; Pineal Gland; Residence
Characteristics; Risk Factors; Secretory Rate; Sleep; Work Schedule Tolerance

Davis, Scott; Mirick, Dana K.; Stevens, Richard G. (2002): Residential magnetic fields and the risk of breast
cancer .In:Amer icanj our
nal ofepi demi ology,J g.155,H.5,S.446– 454.
Abstract Chronic exposure to 60-Hz magnetic fields may increase the risk of breast cancer
by suppressing the normal nocturnal production of melatonin. This population-
based case-control study investigated whether such exposure is associated with an
increased risk of breast cancer in women aged 20-74 years from the greater
Seattle, Washington, area. Cases were diagnosed between November 1992 and
March 1995 (n = 813); controls were identified by random digit dialing and were
frequency matched by 5-year age groups (n = 793). Exposure was estimated using
magnetic field measurements in the home at diagnosis, wiring configuration of all
homes occupied in the 10 years prior to diagnosis, and self-reported measures of
at-home electric appliance use. Odds ratios and 95% confidence intervals were
estimated using conditional logistic regression with adjustment for other potential
risk factors. Risk did not increase with measured nighttime bedroom magnetic field
level, wiring configuration of the home at diagnosis, weighted summary wire codes
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of all homes occupied 5 and 10 years prior to diagnosis, or reported use of common
household appliances, including bed-warming devices. These data do not support
the hypothesis that exposure to residential magnetic fields is associated with an
increased risk of developing breast cancer.
Schlagwörter Adult; Aged; Antioxidants; Breast Neoplasms; Case-Control Studies; Circadian
Rhythm; Electromagnetic Fields; Environmental Exposure; Female; Household
Articles; Housing; Humans; Melatonin; Middle Aged; Risk Assessment; Washington

Erren, T. C.; Stevens, R. G. (2002): [Light, melatonin and internal cancers - recent facts and research
perspectives]. In: Gesundheitswesen (Bundesverband der Ärzte des Öffentlichen Gesundheitsdienstes
(Germany )),J g.64,H.5,S.278–283.Onl inev erf
ügbarunt erdoi :10. 1055/s-
2002- 28352.
Abstract Visible light of sufficient intensity inhibits melatonin biosynthesis and numerous
experimental studies suggest that melatonin may protect against cancer. From a
public health point of view it is important to verify or falsify the hypothesis that
artificial light - or even sunlight itself - suppresses melatonin production sufficiently
to increase the risk of developing cancers of internal organs. Since humans are
exposed universally, even small risk elevations could lead to numerous cases.
Recent epidemiological studies of people exposed to anthropogenic light-at-night in
the course of shift work and first evaluations of natural light experiments in blind
people and in residents of the Arctic are compatible with the possibility that light can
influence - at least hormone- dependent - cancer developments via melatonin. To
systematically investigate the effect of geographically different light intensities on
melatonin production in man, a pan-European study is suggested. Further
epidemiological investigations can contribute to the understanding of the patho-
physiological relationships between light, melatonin and human biology.
Schlagwörter Animals; Causality; Circadian Rhythm; Humans; Light; Melatonin; Neoplasms,
Hormone-Dependent; Risk Factors; Topography, Medical

Hanifin, John P.; Stewart, Karen T.; Smith, Peter; Tanner, Roger; Rollag, Mark; Brainard, George C. (2006):
High-intensit
yr edl ightsuppr es sesmel at
oni n.I n:Chr onobi ologyinternational ,Jg.23,H.1- 2,S.251– 268.Onl i
ne
verfügbar unter doi:10.1080/07420520500521988.
Abstract Early studies on rodents indicated that the long-wavelength portion of the spectrum
(orange- and red-appearing light) could influence circadian and neuroendocrine
responses. Since then, both polychromatic and analytic action spectra in various
rodent species have demonstrated that long-wavelength light is very weak, if not
entirely inactive, for regulating neurobehavioral responses. Since testing of
monochromatic light wavelengths above 600 nm is uncommon, many researchers
have assumed that there is little to no effect of red light on the neuroendocrine or
circadian systems. The aims of the following studies were to test the efficacy of
monochromatic light above 600 nm for melatonin suppression in hamsters and
humans. Results in hamsters show that 640 nm monochromatic light at 1.1 x 10(17)
photons/cm2 can acutely suppress pineal melatonin levels. In normal healthy
humans, equal photon density exposures of 1.9 x 10(18) photons/cm2 at 460, 630,
and 700 nm monochromatic light elicited a significant melatonin suppression at 460
nm and small reductions of plasma melatonin levels at 630 and 700 nm. These
findings are discussed relative to the possible roles of classical visual
photoreceptors and the recently discovered intrinsically photosensitive retinal
ganglion cells for circadian phototransduction. That physiology, and its potential for
responding to red light, has implications for domestic applications involving animal
care, the lighting of typical human environments, and advanced applications such
as space exploration.
Schlagwörter Adult; Animals; Circadian Rhythm; Cricetinae; Female; Humans; Light; Male;
Melatoninmetabolismphysiology; Photic Stimulation; Photons; Pineal
Glandphysiology

Juutilainen, J.; Stevens, R. G.; Anderson, L. E.; Hansen, N. H.; Kilpeläinen, M.; Kumlin, T. et al. (2000):
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Nocturnal 6-hydroxymelatonin sulfate excretion in female workers exposed to magnetic fields. In: Journal of
pineal resear c h,Jg.28,H.2,S.97–104.
Abstract The objective of this study was to determine whether daytime occupational
exposure to extremely low frequency magnetic fields (MFs) suppresses nocturnal
melatonin production. Sixty female volunteers were recruited. Thirty-nine worked in
a garment factory, and 21 office workers served as a reference group. Exposure
assessment was based on the type of sewing machine used and MF
measurements around each type of machine. Eye-level MF flux density was used to
classify the operators to higher (>1 microT) and lower (0.3-1 microT) exposure
categories. A third group of factory workers had diverse MF exposures from other
sources. The reference group had average exposure of about 0.15 microT. Urine
samples were collected on Friday and Monday for three consecutive weeks.
Melatonin production was assessed as urinary 6-hydroxymelatonin sulfate (6-
OHMS) excretion. The ratio of Friday morning/Monday morning 6-OHMS was used
to test the hypothesis that melatonin production is suppressed after 4 days of
occupational MF exposure with significant recovery during the weekend. Possible
chronic suppression of melatonin production was evaluated by studying exposure-
related differences in the Friday values by multivariate regression analysis. The
Monday/Friday ratios were close to 1.0, suggesting that there is no increase in
melatonin production over the weekend. The average 6-OHMS excretion on Friday
was lower among the factory workers than in the reference group, but no
monotonous dose-response was observed. Multivariate regression analysis
identified MF exposure, smoking, and age as significant explanatory variables
associated with decreased 6-OHMS excretion.
Schlagwörter Adult; Circadian Rhythm; Electromagnetic Fields; Female; Humans; Melatonin;
Middle Aged; Occupational Exposure; Pineal Gland; Radioimmunoassay; Textile
Industry

Mainster, M. A. (2006): Violet and blue light blocking intraocular lenses: photoprotection versus photoreception.
I
n:TheBr i
ti
shj ournal ofopht halmol ogy,Jg.90,H.6,S.784– 792.Onl i
nev er
fügbarunt er
doi:10.1136/bjo.2005.086553.
Abstract AIM: To analyse how intraocular lens (IOL) chromophores affect retinal
photoprotection and the sensitivity of scotopic vision, melanopsin photoreception,
and melatonin suppression. METHODS: Transmittance spectra of IOLs, high pass
spectral filters, human crystalline lenses, and sunglasses are used with spectral
data for acute ultraviolet (UV)-blue photic retinopathy ("blue light hazard"
phototoxicity), aphakic scotopic luminous efficiency, melanopsin sensitivity, and
melatonin suppression to compute the effect of spectral filters on retinal
photoprotection, scotopic sensitivity, and circadian photoentrainment. RESULTS:
Retinal photoprotection increases and photoreception decreases as high pass filters
progressively attenuate additional short wavelength light. Violet blocking IOLs
reduce retinal exposure to UV (200-400 nm) radiation and violet (400-440 nm) light.
Blue blocking IOLs attenuate blue (440-500 nm) and shorter wavelength optical
radiation. Blue blocking IOLs theoretically provide better photoprotection but worse
photoreception than conventional UV only blocking IOLs. Violet blocking IOLs offer
similar UV-blue photoprotection but better scotopic and melanopsin photoreception
than blue blocking IOLs. Sunglasses provide roughly 50% more UV-blue
photoprotection than either violet or blue blocking IOLs. CONCLUSIONS: Action
spectra for most retinal photosensitisers increase or peak in the violet part of the
spectrum. Melanopsin, melatonin suppression, and rhodopsin sensitivities are all
maximal in the blue part of the spectrum. Scotopic sensitivity and circadian
photoentrainment decline with ageing. UV blocking IOLs provide older adults with
the best possible rhodopsin and melanopsin sensitivity. Blue and violet blocking
IOLs provide less photoprotection than middle aged crystalline lenses, which do not
prevent age related macular degeneration (AMD). Thus, pseudophakes should
wear sunglasses in bright environments if the unproved phototoxicity-AMD
iLib08 - Citavi
hypothesis is valid.
Schlagwörter Aged; Aging; Child, Preschool; Circadian Rhythm; Eye Protective Devices;
Humans; Lens, Crystalline; Lenses, Intraocular; Melatonin; Middle Aged; Opsin;
Optics; Radiation Protection; Retina; Scattering, Radiation; Scotoma; Ultraviolet
Rays

Moser, Maximilian; Schaumberger, Karin; Schernhammer, Eva; Stevens, Richard G. (2006): Cancer and
rhythm.I n:Canc ercauses&cont r
ol :CCC,Jg.17,H.4,S.483– 487.Onl inever f
ügbarunt er
doi:10.1007/s10552-006-0012-z.
Schlagwörter Animals; Breast Neoplasms; Chronobiology; Chronotherapy; Circadian Rhythm;
Humans; Life Style; Melatonin; Neoplasms; Risk Factors

Pukkala, Eero; Ojamo, Matti; Rudanko, Sirkka-Liisa; Stevens, Richard G.; Verkasalo, Pia K. (2006): Does
incidence of breast cancer and prostate cancer decrease with increasing degree of visual impairment. In:
Cancercaus es&c ontrol:CCC,J g.17,H.4,S.573– 576.Onl inever fügbarunt erdoi
:
10. 1007/ s
10552- 005-9005-
6.
Abstract OBJECTIVE: The issue of light at night and cancer continuously attracts discussion.
The major hypotheses are that melatonin may decrease risk of hormone-related
cancers, particularly breast cancer, or even act as a potent antioxidant and thus
have a protective effect against cancer development in general. METHODS: We
tested the hypothesis that blind persons are at lower risk of cancer in a follow-up
study linking a cohort of 17,557 persons with visual impairment identified from the
Finnish Register of Visual Impairment with cancer incidence data of the Finnish
Cancer Registry for years 1983-2003. RESULTS: Breast cancer risk in females
decreased by degree of visual impairment, and a similar but less consistent trend
was observed for prostate cancer in males. The incidence for the remaining cancers
among nearly to totally blind persons was significantly higher than in average
Finnish population. CONCLUSIONS: Our findings add to the suggestive
epidemiological evidence for a decreased risk of hormone-related cancers in people
with visual impairment and, consequently, a relationship between visible light at
night and breast cancer risk. The result is strongly against the hypothesis of a
systemic protective effect related lack of visible light.
Schlagwörter Blindness; Breast Neoplasms; Female; Humans; Incidence; Light; Male; Middle
Aged; Prostatic Neoplasms; Vision, Low

Reiter, R. J.; Hurlbut, E. C.; Brainard, G. C.; Steinlechner, S.; Richardson, B. A. (1984): Influence of light
irradiance on hydroxyindole-O-methyltransferase activity, serotonin-N-acetyltransferase activity, and
radioimmunoassayable melatonin levels in the pineal gland of the diurnally active Richardson's ground squirrel.
In:Br ainresear ch,J g.288,H.1- 2,S.151– 157.
Abstract When Richardson's ground squirrels were kept under light:dark cycles of 14:10 h
there was no nocturnal rise in pineal hydroxyindole-O-methyltransferase (HIOMT)
activity. Conversely, the 10 h dark period was associated with large nocturnal rises
in both pineal serotonin-N-acetyltransferase (NAT) activity and
radioimmunoassayable melatonin levels. The nighttime rises in pineal NAT and
melatonin were not suppressed by the exposure of the animals to a light irradiance
of 925 mu W/cm2 during the normal dark period. On the other hand, when the light
irradiance was increased to 1850 mu W/cm2 the rise in pineal NAT activity was
eliminated while the melatonin rise was greatly reduced. When ground squirrels
were acutely exposed to a light irradiance of 1850 mu W/cm2 for 30 min beginning
at 5.5 h after lights out, pineal NAT activity and melatonin levels were reduced to
daytime values within 30 min. The half-time (t 1/2) for each constituent was less
than 10 min. Exposure to a light irradiance of either 5 s or 5 min (beginning at 5.5 h
into dark period) was equally as effective as 30 min light exposure in inhibiting
pineal NAT activity and melatonin levels. When animals were returned to darkness
after a 30 min exposure to a light irradiance of 1850 mu W/cm2 at night, both pineal
NAT activity and melatonin levels were restored to high nighttime levels within 2 h
iLib08 - Citavi
of their return to darkness. The results indicate that the pineal gland of the wild-
captured, diurnal Richardson's ground squirrel is 9000 X less sensitive to light at
night than is the pineal gland of the laboratory raised, nocturnal Syrian hamster.
Schlagwörter Acetylserotonin O-Methyltransferasemetabolism; Acetyltransferasesmetabolism;
Animals; Arylamine N-Acetyltransferasemetabolism; Circadian Rhythm; Darkness;
Kinetics; Light; Melatoninmetabolism; Methyltransferasesmetabolism; Pineal
Glandmetabolism; Sciuridaemetabolism

Scheer, F. A.; van Doornen, L. J.; Buijs, R. M. (1999): Light and diurnal cycle affect human heart rate: possible
rol
ef ort hecircadianpac emaker .In:J ournalofbi ologicalr hythms ,J g.14,H.3,S.202–212.
Abstract Humans and animals demonstrate diurnal rhythms in physiology and behavior,
which are generated by the circadian pacemaker, located in the supra-chiasmatic
nucleus (SCN). The endogenous diurnal rhythm of the SCN is synchronized to the
diurnal cycle most effectively by light. However, light also influences the SCN and
its output instantaneously, as is demonstrated for the immediate effects of light on
SCN neuronal firing frequency and on the output of the SCN to the pineal, inhibiting
melatonin secretion. In addition to this, the circadian pacemaker modulates
neuronally also other organs such as the adrenal. Therefore, the authors
investigated the effect of this light input to the SCN on human heart rate, using light
at different phases of the day-night cycle and light of different intensities. Resting
heart rate (HR) was measured in volunteers between 20 and 40 years of age during
supine, awake, resting conditions, and after 2 hours of fasting. In Experiment 1, HR
was measured at different times over the day-night cycle at 0 lux and at indoor light.
In Experiment 2, HR was measured at different times over the day-night cycle at
controlled light intensities of 0 lux, 100 lux, and 800 lux. The authors demonstrate a
clear diurnal rhythm in resting HR in complete darkness, similar to that measured
under constant routine conditions. Second, it is demonstrated that light increases
resting HR depending on the phase of the day-night cycle and on the intensity of
light. These data strongly suggest that the circadian pacemaker modulates human
HR.
Schlagwörter Adult; Analysis of Variance; Biological Clocksphysiology; Circadian
Rhythmphysiology; Dose-Response Relationship, Radiation; Heart
Ratephysiologyradiation effects; Humans; Light; Male

Scheer, F. A. J. L.; Pirovano, C.; van Someren, E. J. W.; Buijs, R. M. (2005): Environmental light and
suprachiasmatic nucleus interact in the regulation of body temperature. In: Neuroscience, Jg. 132, H. 2, S.
465–477.Onl inever f
ügbarunt erdoi :
10. 1016/ j
.neur osc i
enc e.2004.12. 012.
Abstract The mammalian biological clock, located in the suprachiasmatic nucleus (SCN), is
crucial for circadian rhythms in physiology and behavior. However, equivocal
findings have been reported on its role in the circadian regulation of body
temperature. The goal of the present studies was to investigate the interaction
between the SCN and environmental light in the regulation of body temperature. All
recordings were performed by telemetry in free moving male Wistar rats. Firstly, we
demonstrated an endogenous circadian rhythm in body temperature independent of
locomotor activity. This rhythm was abolished by stereotactic lesioning of the SCN.
Secondly, we demonstrated a circadian phase-dependent suppressive effect of light
('negative masking') on body temperature. Light suppressed body temperature
more at the end of the subjective night (circadian time [CT] 22) than in the middle
(CT 6) and at the end (CT 10) of the subjective day. This circadian-phase
dependent suppression was not demonstrated in SCN-lesioned animals.
Surprisingly, after half a year of recovery from lesioning of the SCN, light regained
its suppressing action on body temperature, resulting in a daily body temperature
rhythm only under light-dark conditions. In contrast to body temperature, light could
not substantially mimic a daytime inhibitory SCN-output in the regulation of heart
rate and locomotor activity. The present results suggest that, after lesioning of the
SCN as main relay station for the immediate body temperature-inhibition by light,
iLib08 - Citavi
secondary relay nuclei can fully take over this function of the SCN. These findings
provide a possible explanation for the controversy in literature over the question
whether the SCN is required for the diurnal rhythm in body temperature.
Furthermore, they show that light may have an acute effect on behavior and
physiology of the organism via the SCN, which extends beyond the generally
acknowledged effect on melatonin secretion.
Schlagwörter Analysis of Variance; Animals; Body Temperaturephysiology; Chi-Square
Distribution; Circadian Rhythmphysiology; Heart Ratephysiology; Light; Male; Motor
Activityphysiology; Photic Stimulation; Rats; Rats, Wistar; Suprachiasmatic
Nucleusphysiology; Time Factors

Scheer, Frank A.; Kalsbeek, Andries; Buijs, Ruud M. (2003): Cardiovascular control by the suprachiasmatic
nucleus: neural and neuroendocrine mechanisms in human and rat. In: Biological chemistry, Jg. 384, H. 5, S.
697– 709.Onl i
never f
ügbarunt erdoi :10.
1515/ BC. 2003.078.
Abstract The risk for cardiovascular incidents is highest in the early morning, which seems
partially due to endogenous factors. Endogenous circadian rhythms in mammalian
physiology and behavior are regulated by the suprachiasmatic nucleus (SCN).
Recently, anatomical evidence has been provided that SCN functioning is disturbed
in patients with essential hypertension. Here we review neural and neuroendocrine
mechanisms by which the SCN regulates the cardiovascular system. First, we
discuss evidence for an endogenous circadian rhythm in cardiac activity, both in
humans and rats, which is abolished after SCN lesioning in rats. The immediate
impact of retinal light exposure at night on SCN-output to the cardiovascular
system, which signals 'day' in both diurnal (human) and nocturnal (rat) mammals
with opposite effects on physiology, is discussed. Furthermore, we discuss the
impact of melatonin treatment on the SCN and its potential medical relevance in
patients with essential hypertension. Finally, we argue that regional differentiation of
the SCN and autonomous nervous system is required to explain the multitude of
circadian rhythms. Insights into the mechanisms by which the SCN affects the
cardiovascular system may provide new strategies for the treatment of disease
conditions known to coincide with circadian rhythm disturbances, as is presented for
essential hypertension.
Schlagwörter Animals; Autonomic Nervous Systemphysiology; Cardiovascular Physiological
Phenomena; Circadian Rhythmphysiology; Heart Ratephysiology; Humans; Light;
Melatoninphysiology; Neurosecretory Systemsphysiology; Rats; Suprachiasmatic
Nucleusphysiology

Scheer, Frank A. J. L.; van Montfrans, Gert A.; van Someren, Eus J. W.; Mairuhu, Gideon; Buijs, Ruud M.
(2004): Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. In:
Hyper t
ens i
on,J g.43,H.2,S.192– 197.Onl inever fügbarunt erdoi :10.1161/01. HYP. 0000113293. 15186.3b.
Abstract Patients with essential hypertension have disturbed autonomic cardiovascular
regulation and circadian pacemaker function. Recently, the biological clock was
shown to be involved in autonomic cardiovascular regulation. Our objective was to
determine whether enhancement of the functioning of the biological clock by
repeated nighttime melatonin intake might reduce ambulatory blood pressure in
patients with essential hypertension. We conducted a randomized, double-blind,
placebo-controlled, crossover trial in 16 men with untreated essential hypertension
to investigate the influence of acute (single) and repeated (daily for 3 weeks) oral
melatonin (2.5 mg) intake 1 hour before sleep on 24-hour ambulatory blood
pressure and actigraphic estimates of sleep quality. Repeated melatonin intake
reduced systolic and diastolic blood pressure during sleep by 6 and 4 mm Hg,
respectively. The treatment did not affect heart rate. The day-night amplitudes of
the rhythms in systolic and diastolic blood pressures were increased by 15% and
25%, respectively. A single dose of melatonin had no effect on blood pressure.
Repeated (but not acute) melatonin also improved sleep. Improvements in blood
pressure and sleep were statistically unrelated. In patients with essential
iLib08 - Citavi
hypertension, repeated bedtime melatonin intake significantly reduced nocturnal
blood pressure. Future studies in larger patient group should be performed to define
the characteristics of the patients who would benefit most from melatonin intake.
The present study suggests that support of circadian pacemaker function may
provide a new strategy in the treatment of essential hypertension.
Schlagwörter Adult; Aged; Antihypertensive Agentsadministration & dosagetherapeutic use;
Blood Pressuredrug effects; Blood Pressure Monitoring, Ambulatory; Circadian
Rhythm; Cross-Over Studies; Double-Blind Method; Humans; Hypertensiondrug
therapy; Male; Melatoninadministration & dosagetherapeutic use; Middle Aged;
Sleep; Wakefulness

Stevens, R. G. (1993): Breast cancer and electric power. In: Biomedicine & pharmacotherapy = Biomédecine &
pharmacot hérapi e,Jg.47,H.10,S.435– 438.
Abstract Breast cancer is a leading cause of death among women in industrialized societies.
It is far less common in less industrialized nations and the reason for this difference
is unclear. One possibility is the distribution and use of electricity which results in
two new exposures in the human environment: light-at-night and electromagnetic
fields. These can reduce nocturnal melatonin production. Melatonin, in turn, has a
protective effect on breast cancer in experimental animals.
Schlagwörter Animals; Breast Neoplasms; Electricity; Electromagnetic Fields; Female; Humans;
Male; Melatonin; Rats

Stevens, R. G. (1993): Biologically based epidemiological studies of electric power and cancer. In:
Environment alheal t
hper spect i
ves ,J g.101Suppl 4,S.93– 100.
Abstract As societies industrialize, the health profile of the population changes; in general,
acute infectious disease declines and chronic disease increases. Use of electricity
is a hallmark of the industrialization process, but there has been no suspicion that
electricity could increase the risk of cancer. Recently, however, a number of
epidemiologic studies have suggested that electromagnetic fields (EMF) may do
just that. Although few cancer experiments have been done yet, there are a number
of biological effects of EMF reported in the literature that might provide bases for
designing cancer experiments and epidemiologic studies. These include effects of
EMF on: a) DNA transcription and translation, b) calcium balance in cells, and c)
pineal production of melatonin. Alterations in DNA transcription and translation
could have pleiotropic effects. Disruption of calcium homeostasis has many
implications including oncogene activation, promotional activity via protein kinases
and ornithine decarboxylase (ODC), and increasing oxidative stress. Reduction of
melatonin suggests a possible increased risk of cancers of hormone-dependent
tissues such as breast and prostate. The idea that a cancer-causing agent must
either be an initiator or a promoter should be discarded; indeed, the
phenomenologic meaning of these two terms has become confused with imputed
mechanistic necessity in recent years. Agents that affect division of normal cells or
of fully transformed cells can play an important role in clinical cancer development
quite apart from initiation or promotion.(ABSTRACT TRUNCATED AT 250
WORDS)
Schlagwörter Calcium; DNA; Electromagnetic Fields; Environmental Monitoring; Forecasting;
Humans; Melatonin; Models, Biological; Neoplasms

Stevens, R. G.; Davis, S. (1996): The melatonin hypothesis: electric power and breast cancer. In: Environmental
healt
hper spect ives,Jg.104Suppl 1,S.135–140.
Abstract Breast cancer is a disease of modern life. As societies industrialize, risk increases,
yet it is unclear which of the myriad changes coming with industrialization drives this
increase. One important hallmark of modern life is the pervasive use of electric
power. Electric power produces light at night (LAN) and electric and magnetic fields
(EMF), either or both of which may alter pineal function and its primary hormone
melatonin, thereby, perhaps increasing the risk of breast cancer. This hypothesis,
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stated a decade ago, is now receiving considerable experimental and
epidemiological attention. The circumstantial case for the hypothesis has three
aspects: light effects on melatonin, EMF effects on melatonin, and melatonin effects
on breast cancer. The strongest of these aspects is the effects of light on melatonin.
It is clear that the normal nocturnal melatonin rise in humans can be suppressed by
light of sufficient intensity. The evidence for an effect of melatonin on breast cancer
in experimental animals is strong, but the evidence in humans is scant and difficult
to gather. The weakest aspect of the circumstantial case is EMF effects on
melatonin. Whereas a half dozen independent laboratories have published findings
of suppression in animals, there are inconsistencies, and there are no published
data on humans. The direct evidence bearing on the hypothesis is sparse but
provocative. Two laboratories have published data showing substantial increases in
chemically induced breast cancer in rats by a weak AC (alternating current)
magnetic field. The epidemiological evidence is very limited but has offered some
support as well. An effect of electric power on breast cancer would have profound
implications, and this possibility deserves continued investigation.
Schlagwörter Animals; Anticarcinogenic Agents; Breast Neoplasms; Electromagnetic Fields;
Humans; Light; Melatonin; Power Plants

Stevens, R. G.; Davis, S.; Thomas, D. B.; Anderson, L. E.; Wilson, B. W. (1992): Electric power, pineal function,
and the risk of breast cancer. In: The FASEB journal : official publication of the Federation of American Societies
f
orExper i
ment alBiology,Jg.6,H.3,S.853–860.
Abstract Breast cancer is the leading cause of cancer death in women in the industrialized
world, and the rates of breast cancer incidence are rising. Although risk is high in
industrialized societies, it is low in nonindustrialized areas. The search for the
causes of breast cancer has not yet yielded a convincing explanation for the
geographic and temporal patterns in the occurrence of breast cancer. Generation of
electric power is a hallmark of industrialization, and two products of electric power,
light-at-night (LAN) and electromagnetic fields (EMF), may affect breast cancer risk.
Exposure to either LAN or EMF can decrease production of melatonin by the pineal
gland. Melatonin, in turn, has been shown to suppress mammary tumorigenesis in
experimental animals. Moreover, recent epidemiological findings indicate an
increased risk of breast cancer in workers occupationally exposed to EMF. On the
basis of these considerations, it is proposed that the use of electrical power
accounts, in part, for the higher risks of breast cancer in industrialized societies.
Schlagwörter Animals; Breast Neoplasms; Dietary Fats; Electricity; Electromagnetic Fields;
Ethanol; Female; Fertility; Humans; Light; Male; Melatonin; Pineal Gland; Prostatic
Neoplasms; Rats; Risk Factors

Stevens, R. G.; Rea, M. S. (2001): Light in the built environment: potential role of circadian disruption in
endocrinedi sr
upt i
onandbr eas tcanc er .I
n:Canc erc aus es&c ontrol:CCC,J g.12,H.3,S.279–287.
Abstract Life in industrialized societies is primarily life inside buildings. Illumination from
electric lighting in the built environment is quite different from solar radiation in
intensity, spectral content, and timing during the 24-hour daily period. Humans
evolved over millions of years with the day-night pattern of solar radiation as the
primary circadian cue. This pattern maintained a 24-hour rhythm of melatonin
release, as well as a host of other physiological rhythms including the sleep-wake
cycle. Electric lighting in the built environment is generally more than sufficient for
visual performance, but may be inappropriate for the maintenance of normal
neuroendocrine rhythms in humans; e.g., insufficient during the day and too much
at night. Lighting standards and engineering stress visual performance, whereas
circadian function is not currently emphasized. The molecular biological research on
the circadian clock and on mechanisms of phototransduction makes it clear that
light for vision and light for circadian function are not identical systems. In particular,
if electric lighting as currently employed contributes to 'circadian disruption' it may
be an important cause of 'endocrine disruption' and thereby contribute to a high risk
iLib08 - Citavi
of breast cancer in industrialized societies.
Schlagwörter Adult; Breast Neoplasms; Circadian Rhythm; Developed Countries; Endocrine
Glands; Environmental Exposure; Estrogens; Fear; Female; Humans; Lighting;
Melatonin; Menstrual Cycle; Sleep Deprivation; Stress, Psychological

Stevens, Richard G. (2002): Light at night and breast cancer: an editorial correction. In: Epidemiology
(Cambridge, Mass.), Jg. 13, H. 1, S. 116.
Schlagwörter Breast Neoplasms; Darkness; Electricity; Estrogens; Female; Humans; Light;
Melatonin; Pineal Gland

Stevens, Richard G. (2005): Circadian disruption and breast cancer: from melatonin to clock genes. In:
Epidemi ol
ogy( Cambr idge,Mas s.)
,Jg.16,H.2,S.254– 258.
Abstract The global impact of breast cancer is large and growing. It seems clear that
something about modern life is the culprit, yet there is thus far a lack of satisfactory
explanations for most of the increases in risk as societies industrialize. Support has
developed for a possible role of "circadian disruption," particularly from an altered-
lighted environment (such as light at night). Lighting during the night of sufficient
intensity can disrupt circadian rhythms, including reduction of circulating melatonin
levels and resetting of the circadian pacemaker of the suprachiasmatic nuclei.
Reduced melatonin may increase breast cancer risk through several mechanisms,
including increased estrogen production and altered estrogen receptor function. The
genes that drive the circadian rhythm are emerging as central players in gene
regulation throughout the organism, particularly for cell-cycle regulatory genes and
the genes of apoptosis. Aspects of modern life that can disrupt circadian rhythms
during the key developmental periods (eg, in utero and during adolescence) may be
particularly harmful. Epidemiologic studies should consider gene and environment
interactions such as circadian gene variants and shift work requirements on the job.
Schlagwörter Breast Neoplasms; Cell Cycle; Circadian Rhythm; Epidemiologic Studies; Female;
Gene Expression Regulation; Humans; Light; Melatonin; Photoperiod; Risk Factors

Stevens, Richard G. (2006): Artificial lighting in the industrialized world: circadian disruption and breast cancer.
I
n:Cancercaus es&c ontr
ol :CCC,J g.17,H.4,S.501– 507.Onl i
never fügbarunt erdoi :10.1007/ s10552- 005-
9001-x.
Abstract Breast cancer risk is high in industrialized societies, and increases as developing
countries become more Westernized. The reasons are poorly understood. One
possibility is circadian disruption from aspects of modern life, in particular the
increasing use of electric power to light the night, and provide a sun-free
environment during the day inside buildings. Circadian disruption could lead to
alterations in melatonin production and in changing the molecular time of the
circadian clock in the suprachiasmatic nuclei (SCN). There is evidence in humans
that the endogenous melatonin rhythm is stronger for persons in a bright-day
environment than in a dim-day environment; and the light intensity necessary to
suppress melatonin at night continues to decline as new experiments are done.
Melatonin suppression can increase breast tumorigenesis in experimental animals,
and altering the endogenous clock mechanism may have downstream effects on
cell cycle regulatory genes pertinent to breast tissue development and
susceptibility. Therefore, maintenance of a solar day-aligned circadian rhythm in
endogenous melatonin and in clock gene expression by exposure to a bright day
and a dark night, may be a worthy goal. However, exogenous administration of
melatonin in an attempt to achieve this goal may have an untoward effect given that
pharmacologic dosing with melatonin has been shown to phase shift humans
depending on the time of day it's given. Exogenous melatonin may therefore
contribute to circadian disruption rather than alleviate it.
Schlagwörter Alcohol Drinking; Animals; Breast Neoplasms; Chronobiology Disorders; Circadian
Rhythm; Developing Countries; Female; Humans; Lighting; Melatonin; Risk Factors;
Suprachiasmatic Nucleus
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Stevens, Richard G.; Blask, David E.; Brainard, George C.; Hansen, Johnni; Lockley, Steven W.; Provencio,
Ignacio et al. (2007): Meeting report: the role of environmental lighting and circadian disruption in cancer and
otherdi seases.I n:Env i
ronment al heal t
hper spec tives,J g.115,H.9,S.1357–1362.Onl i
nev erf
ügbarunt er
doi:10.1289/ehp.10200.
Abstract Light, including artificial light, has a range of effects on human physiology and
behavior and can therefore alter human physiology when inappropriately timed.
One example of potential light-induced disruption is the effect of light on circadian
organization, including the production of several hormone rhythms. Changes in
light-dark exposure (e.g., by nonday occupation or transmeridian travel) shift the
timing of the circadian system such that internal rhythms can become
desynchronized from both the external environment and internally with each other,
impairing our ability to sleep and wake at the appropriate times and compromising
physiologic and metabolic processes. Light can also have direct acute effects on
neuroendocrine systems, for example, in suppressing melatonin synthesis or
elevating cortisol production that may have untoward long-term consequences. For
these reasons, the National Institute of Environmental Health Sciences convened a
workshop of a diverse group of scientists to consider how best to conduct research
on possible connections between lighting and health. According to the participants
in the workshop, there are three broad areas of research effort that need to be
addressed. First are the basic biophysical and molecular genetic mechanisms for
phototransduction for circadian, neuroendocrine, and neurobehavioral regulation.
Second are the possible physiologic consequences of disrupting these circadian
regulatory processes such as on hormone production, particularly melatonin, and
normal and neoplastic tissue growth dynamics. Third are effects of light-induced
physiologic disruption on disease occurrence and prognosis, and how prevention
and treatment could be improved by application of this knowledge.
Schlagwörter Animals; Circadian Rhythm; Environmental Exposure; Humans; Lightingadverse
effects; Neoplasmsetiology; Research

Stevens, Richard G.; Schernhammer, Eva (2005): Epidemiology of urinary melatonin in women and its relation
to other hormones and night work. In: Cancer epidemiology, biomarkers & prevention : a publication of the
American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, Jg.
14, H. 2, S. 551; author reply 551. Online verfügbar unter doi:10.1158/1055-9965.EPI-04-0420.
Schlagwörter Breast Neoplasms; Female; Hormones; Humans; Light; Melatonin; Work Schedule
Tolerance

Vaughan, G. M.; McDonald, S. D.; Jordan, R. M.; Allen, J. P.; Bell, R.; Stevens, E. A. (1979): Melatonin, pituitary
f
unc t
ionands t
ressinhumans.I n:Ps y
choneur oendocr inol ogy ,Jg.4,H.4,S.351– 362.
Schlagwörter Adrenocorticotropic Hormone; Adult; Circadian Rhythm; Endocrine System
Diseases; Exertion; Female; Follicle Stimulating Hormone; Growth Hormone;
Humans; Hydrocortisone; Levodopa; Luteinizing Hormone; Male; Melatonin;
Pituitary Gland; Stress; Thyrotropin

Verkasalo, P. K.; Pukkala, E.; Stevens, R. G.; Ojamo, M.; Rudanko, S. L. (1999): Inverse association between
breast cancer incidence and degree of visual impairment in Finland. In: British journal of cancer, Jg. 80, H. 9, S.
1459–1460.Onl i
never fügbarunt erdoi :
10.1038/s j
.bj
c.6690544.
Abstract A total of 10935 women with visual impairment were identified from the Finnish
Register of Visual Impairment and followed up for cancer through the Finnish
Cancer Registry for years 1983-1996. Breast cancer risk decreased by degree of
visual impairment (P for trend 0.04) which suggests a dose-response relationship
between visible light and breast cancer risk.
Schlagwörter Adolescent; Adult; Aged; Breast Neoplasms; Female; Finland; Humans; Incidence;
Melatonin; Middle Aged; Vision Disorders

Verkasalo, Pia K.; Lillberg, Kirsi; Stevens, Richard G.; Hublin, Christer; Partinen, Markku; Koskenvuo, Markku;
iLib08 - Citavi
Kaprio, Jaakko (2005): Sleep duration and breast cancer: a prospective cohort study. In: Cancer research, Jg.
65,H.20,S.9595– 9600.Onl inev erfügbarunt erdoi :
10.1158/ 0008- 5472. CAN- 05-2138.
Abstract Breast cancer incidence has increased during recent decades for reasons that are
only partly understood. Prevalence of sleeping difficulties and sleepiness has
increased, whereas sleeping duration per night has decreased. We hypothesized
that there is an inverse association between sleep duration and breast cancer risk,
possibly due to greater overall melatonin production in longer sleepers. This
population-based study includes information from women born in Finland before
1958. Sleep duration, other sleep variables, and breast cancer risk factors were
assessed by self-administered questionnaires given in 1975 and in 1981. Breast
cancer incidence data for 1976 to 1996 was obtained from the Finnish Cancer
Registry. Hazard ratios (HR) and 95% confidence intervals (CI) were obtained from
Cox proportional hazards models adjusting for potential confounders. Altogether,
242 cases of breast cancer occurred over the study period among the 12,222
women with sleep duration data in 1975. For these women, the HRs for breast
cancer in the short (< or =6 hours), average (7-8 hours), and long sleep (> or =9
hours) duration groups were 0.85 (CI, 0.54-1.34), 1.0 (referent), and 0.69 (CI, 0.45-
1.06), respectively. Analysis restricted to the 7,396 women (146 cases) whose
sleep duration in 1975 and 1981 were in the same duration group (stable sleepers)
yielded HRs of 1.10 (CI, 0.59-2.05), 1.0, and 0.28 (CI, 0.09-0.88), with a decreasing
trend (P = 0.03). This study provides some support for a decreased risk of breast
cancer in long sleepers.
Schlagwörter Adult; Breast Neoplasms; Cohort Studies; Female; Humans; Middle Aged;
Prospective Studies; Questionnaires; Risk Factors; Sleep; Sleep Disorders; Twin
Studies as Topic; Twins

Wilson, B. W.; Stevens, R. G.; Anderson, L. E. (1989): Neuroendocrine mediated effects of electromagnetic-field
exposur e:pos siblerol
eoft hepi neal gl and.In:Lifes ci
ences,J g.45,H.15,S.1319–1332.
Abstract Reports from recent epidemiological studies have suggested a possible association
between extremely low frequency (ELF; including 50- or 60-Hz) electric- and
magnetic-field exposure, and increased risk of certain cancers, depression, and
miscarriage. ELF field-induced pineal gland dysfunction is a possible etiological
factor in these effects. Work in our laboratory and elsewhere has shown that ELF
electromagnetic-field exposure can alter the normal circadian rhythm of melatonin
synthesis and release in the pineal gland. Consequences of reduced or
inappropriately timed melatonin release on the endocrine, neuronal, and immune
systems are discussed. Laboratory data linking ELF field exposure to changes in
pineal circadian rhythms in both animals and humans are reviewed. The authors
suggest that the pineal gland, in addition to being a convenient locus for measuring
dyschronogenic effects of ELF field exposure, may play a central role in biological
response to these fields via alterations in the melatonin signal.
Schlagwörter Animals; Electromagnetic Fields; Electromagnetics; Humans; Neurosecretory
Systems; Pineal Gland; Rats

Zaidi, Farhan H.; Hull, Joseph T.; Peirson, Stuart N.; Wulff, Katharina; Aeschbach, Daniel; Gooley, Joshua J. et
al. (2007): Short-wavelength light sensitivity of circadian, pupillary, and visual awareness in humans lacking an
out erreti
na.I n:Cur r
entbi ol
ogy:CB,Jg.17,H.24,S.2122–2128.Onl i
never fügbarunter
doi:10.1016/j.cub.2007.11.034.
Abstract As the ear has dual functions for audition and balance, the eye has a dual role in
detecting light for a wide range of behavioral and physiological functions separate
from sight. These responses are driven primarily by stimulation of photosensitive
retinal ganglion cells (pRGCs) that are most sensitive to short-wavelength (
approximately 480 nm) blue light and remain functional in the absence of rods and
cones. We examined the spectral sensitivity of non-image-forming responses in two
profoundly blind subjects lacking functional rods and cones (one male, 56 yr old;
one female, 87 yr old). In the male subject, we found that short-wavelength light
iLib08 - Citavi
preferentially suppressed melatonin, reset the circadian pacemaker, and directly
enhanced alertness compared to 555 nm exposure, which is the peak sensitivity of
the photopic visual system. In an action spectrum for pupillary constriction, the
female subject exhibited a peak spectral sensitivity (lambda(max)) of 480 nm,
matching that of the pRGCs but not that of the rods and cones. This subject was
also able to correctly report a threshold short-wavelength stimulus ( approximately
480 nm) but not other wavelengths. Collectively these data show that pRGCs
contribute to both circadian physiology and rudimentary visual awareness in
humans and challenge the assumption that rod- and cone-based photoreception
mediate all "visual" responses to light.
Schlagwörter Aged, 80 and over; Awarenessphysiology; Blindnessphysiopathology; Circadian
Rhythmphysiology; Female; Humans; Light; Male; Middle Aged; Reflex,
Pupillaryphysiology; Retinaabnormalities; Retinal Ganglion Cellsphysiology