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Author Blask, D.E.; Brainard, G.C.; Dauchy, R.T.; Hanifin, J.P.; Davidson, L.K.; Krause, J.A.; Sauer, L.A.; Rivera-Bermudez, M.A.; Dubocovich, M.L.; Jasser, S.A.; Lynch, D.T.; Rollag, M.D.; Zalatan, F.
Title Melatonin-depleted blood from premenopausal women exposed to light at night stimulates growth of human breast cancer xenografts in nude rats Type Journal Article
Year 2005 Publication Cancer Research Abbreviated Journal Cancer Res
Volume 65 Issue (up) 23 Pages 11174-11184
Keywords Human Health; Animals; Breast Neoplasms/*blood/genetics/pathology; Cell Growth Processes/physiology; Circadian Rhythm/*physiology; Female; Humans; Light; Liver Neoplasms, Experimental/metabolism; Male; Melatonin/blood/*deficiency; Premenopause/blood; RNA, Messenger/biosynthesis/genetics; Rats; Rats, Nude; Receptors, Melatonin/biosynthesis/genetics; Transplantation, Heterologous
Abstract The increased breast cancer risk in female night shift workers has been postulated to result from the suppression of pineal melatonin production by exposure to light at night. Exposure of rats bearing rat hepatomas or human breast cancer xenografts to increasing intensities of white fluorescent light during each 12-hour dark phase (0-345 microW/cm2) resulted in a dose-dependent suppression of nocturnal melatonin blood levels and a stimulation of tumor growth and linoleic acid uptake/metabolism to the mitogenic molecule 13-hydroxyoctadecadienoic acid. Venous blood samples were collected from healthy, premenopausal female volunteers during either the daytime, nighttime, or nighttime following 90 minutes of ocular bright, white fluorescent light exposure at 580 microW/cm2 (i.e., 2,800 lx). Compared with tumors perfused with daytime-collected melatonin-deficient blood, human breast cancer xenografts and rat hepatomas perfused in situ, with nocturnal, physiologically melatonin-rich blood collected during the night, exhibited markedly suppressed proliferative activity and linoleic acid uptake/metabolism. Tumors perfused with melatonin-deficient blood collected following ocular exposure to light at night exhibited the daytime pattern of high tumor proliferative activity. These results are the first to show that the tumor growth response to exposure to light during darkness is intensity dependent and that the human nocturnal, circadian melatonin signal not only inhibits human breast cancer growth but that this effect is extinguished by short-term ocular exposure to bright, white light at night. These mechanistic studies are the first to provide a rational biological explanation for the increased breast cancer risk in female night shift workers.
Address Laboratory of Chrono-Neuroendocrine Oncology, Bassett Research Institute, The Mary Imogene Bassett Hospital, Cooperstown, New York 13326, USA. david.blask@bassett.org
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0008-5472 ISBN Medium
Area Expedition Conference
Notes PMID:16322268 Approved no
Call Number LoNNe @ kagoburian @ Serial 721
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Author Gooley, J.J.; Chamberlain, K.; Smith, K.A.; Khalsa, S.B.S.; Rajaratnam, S.M.W.; Van Reen, E.; Zeitzer, J.M.; Czeisler, C.A.; Lockley, S.W.
Title Exposure to room light before bedtime suppresses melatonin onset and shortens melatonin duration in humans Type Journal Article
Year 2011 Publication The Journal of Clinical Endocrinology and Metabolism Abbreviated Journal J Clin Endocrinol Metab
Volume 96 Issue (up) 3 Pages E463-72
Keywords Adolescent; Adult; Female; Humans; *Light; *Lighting; Male; Melatonin/*blood; Sleep/physiology; Time Factors; Young Adult
Abstract CONTEXT: Millions of individuals habitually expose themselves to room light in the hours before bedtime, yet the effects of this behavior on melatonin signaling are not well recognized. OBJECTIVE: We tested the hypothesis that exposure to room light in the late evening suppresses the onset of melatonin synthesis and shortens the duration of melatonin production. DESIGN: In a retrospective analysis, we compared daily melatonin profiles in individuals living in room light (<200 lux) vs. dim light (<3 lux). PATIENTS: Healthy volunteers (n = 116, 18-30 yr) were recruited from the general population to participate in one of two studies. SETTING: Participants lived in a General Clinical Research Center for at least five consecutive days. INTERVENTION: Individuals were exposed to room light or dim light in the 8 h preceding bedtime. OUTCOME MEASURES: Melatonin duration, onset and offset, suppression, and phase angle of entrainment were determined. RESULTS: Compared with dim light, exposure to room light before bedtime suppressed melatonin, resulting in a later melatonin onset in 99.0% of individuals and shortening melatonin duration by about 90 min. Also, exposure to room light during the usual hours of sleep suppressed melatonin by greater than 50% in most (85%) trials. CONCLUSIONS: These findings indicate that room light exerts a profound suppressive effect on melatonin levels and shortens the body's internal representation of night duration. Hence, chronically exposing oneself to electrical lighting in the late evening disrupts melatonin signaling and could therefore potentially impact sleep, thermoregulation, blood pressure, and glucose homeostasis.
Address Division of Sleep Medicine, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Avenue, Boston, Massachusetts 02115, USA. gmsjjg@nus.edu
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0021-972X ISBN Medium
Area Expedition Conference
Notes PMID:21193540; PMCID:PMC3047226 Approved no
Call Number IDA @ john @ Serial 139
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Author Smith, M.R.; Revell, V.L.; Eastman, C.I.
Title Phase advancing the human circadian clock with blue-enriched polychromatic light Type Journal Article
Year 2009 Publication Sleep Medicine Abbreviated Journal Sleep Med
Volume 10 Issue (up) 3 Pages 287-294
Keywords Adult; Circadian Rhythm/*radiation effects; Female; Humans; *Light; Lighting/*methods; Male; Melatonin/metabolism; Phototherapy/*methods; Sleep; Wakefulness; Young Adult; blue light; sleep
Abstract BACKGROUND: Previous studies have shown that the human circadian system is maximally sensitive to short-wavelength (blue) light. Whether this sensitivity can be utilized to increase the size of phase shifts using light boxes and protocols designed for practical settings is not known. We assessed whether bright polychromatic lamps enriched in the short-wavelength portion of the visible light spectrum could produce larger phase advances than standard bright white lamps. METHODS: Twenty-two healthy young adults received either a bright white or bright blue-enriched 2-h phase advancing light pulse upon awakening on each of four treatment days. On the first treatment day the light pulse began 8h after the dim light melatonin onset (DLMO), on average about 2h before baseline wake time. On each subsequent day, light treatment began 1h earlier than the previous day, and the sleep schedule was also advanced. RESULTS: Phase advances of the DLMO for the blue-enriched (92+/-78 min, n=12) and white groups (76+/-45 min, n=10) were not significantly different. CONCLUSION: Bright blue-enriched polychromatic light is no more effective than standard bright light therapy for phase advancing circadian rhythms at commonly used therapeutic light levels.
Address Biological Rhythms Research Laboratory, Rush University Medical Center, Suite 425, 1645 W. Jackson Boulevard, Chicago, IL 60612, USA
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1389-9457 ISBN Medium
Area Expedition Conference
Notes PMID:18805055; PMCID:PMC2723863 Approved no
Call Number IDA @ john @ Serial 289
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Author Chellappa, S.L.; Viola, A.U.; Schmidt, C.; Bachmann, V.; Gabel, V.; Maire, M.; Reichert, C.F.; Valomon, A.; Gotz, T.; Landolt, H.-P.; Cajochen, C.
Title Human melatonin and alerting response to blue-enriched light depend on a polymorphism in the clock gene PER3 Type Journal Article
Year 2012 Publication The Journal of Clinical Endocrinology and Metabolism Abbreviated Journal J Clin Endocrinol Metab
Volume 97 Issue (up) 3 Pages E433-7
Keywords Adult; Alleles; Cross-Over Studies; Female; Genotype; Homozygote; Humans; *Light; Male; Melatonin/*blood/genetics; *Minisatellite Repeats; Period Circadian Proteins/*genetics; *Polymorphism, Genetic; Questionnaires; Sleep/genetics; Wakefulness/*genetics
Abstract CONTEXT: Light exposure, particularly at the short-wavelength range, triggers several nonvisual responses in humans. However, the extent to which the melatonin-suppressing and alerting effect of light differs among individuals remains unknown. OBJECTIVE: Here we investigated whether blue-enriched polychromatic light impacts differentially on melatonin and subjective and objective alertness in healthy participants genotyped for the PERIOD3 (PER3) variable-number, tandem-repeat polymorphism. DESIGN, SETTING, AND PARTICIPANTS: Eighteen healthy young men homozygous for the PER3 polymorphism (PER3(5/5)and PER3(4/4)) underwent a balanced crossover design during the winter season, with light exposure to compact fluorescent lamps of 40 lux at 6500 K and at 2500 K during 2 h in the evening. RESULTS: In comparison to light at 2500 K, blue-enriched light at 6500 K induced a significant suppression of the evening rise in endogenous melatonin levels in PER3(5/5) individuals but not in PER3(4/4). Likewise, PER3(5/5) individuals exhibited a more pronounced alerting response to light at 6500 K than PER3(4/4) volunteers. Waking electroencephalographic activity in the theta range (5-7 Hz), a putative correlate of sleepiness, was drastically attenuated during light exposure at 6500 K in PER3(5/5) individuals as compared with PER3(4/4). CONCLUSIONS: We provide first evidence that humans homozygous for the PER3 5/5 allele are particularly sensitive to blue-enriched light, as indexed by the suppression of endogenous melatonin and waking theta activity. Light sensitivity in humans may be modulated by a clock gene polymorphism implicated in the sleep-wake regulation.
Address Centre for Chronobiology, Psychiatric Hospital of the University of Basel, Wilhelm Kleinstrasse 27, CH-4012 Basel, Switzerland
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0021-972X ISBN Medium
Area Expedition Conference
Notes PMID:22188742 Approved no
Call Number IDA @ john @ Serial 301
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Author Cajochen, C.; Munch, M.; Kobialka, S.; Krauchi, K.; Steiner, R.; Oelhafen, P.; Orgul, S.; Wirz-Justice, A.
Title High sensitivity of human melatonin, alertness, thermoregulation, and heart rate to short wavelength light Type Journal Article
Year 2005 Publication The Journal of Clinical Endocrinology and Metabolism Abbreviated Journal J Clin Endocrinol Metab
Volume 90 Issue (up) 3 Pages 1311-1316
Keywords Human Health; Adult; Body Temperature Regulation/physiology/*radiation effects; Circadian Rhythm/physiology/radiation effects; Color; Heart Rate/physiology/*radiation effects; Humans; *Light; Male; Melatonin/*metabolism; Retinal Cone Photoreceptor Cells/physiology; Sleep Stages/physiology/radiation effects; Wakefulness/physiology/*radiation effects
Abstract Light can elicit acute physiological and alerting responses in humans, the magnitude of which depends on the timing, intensity, and duration of light exposure. Here, we report that the alerting response of light as well as its effects on thermoregulation and heart rate are also wavelength dependent. Exposure to 2 h of monochromatic light at 460 nm in the late evening induced a significantly greater melatonin suppression than occurred with 550-nm monochromatic light, concomitant with a significantly greater alerting response and increased core body temperature and heart rate ( approximately 2.8 x 10(13) photons/cm(2)/sec for each light treatment). Light diminished the distal-proximal skin temperature gradient, a measure of the degree of vasoconstriction, independent of wavelength. Nonclassical ocular photoreceptors with peak sensitivity around 460 nm have been found to regulate circadian rhythm function as measured by melatonin suppression and phase shifting. Our findings-that the sensitivity of the human alerting response to light and its thermoregulatory sequelae are blue-shifted relative to the three-cone visual photopic system-indicate an additional role for these novel photoreceptors in modifying human alertness, thermophysiology, and heart rate.
Address Centre for Chronobiology, Psychiatric University Clinic, Wilhelm Kleinstr. 27, CH-4025 Basel, Switzerland. christian.cajochen@pukbasel.ch
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0021-972X ISBN Medium
Area Expedition Conference
Notes PMID:15585546 Approved no
Call Number LoNNe @ kagoburian @ Serial 728
Permanent link to this record