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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 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 Reiter, R.J.; Tan, D.X.; Korkmaz, A.; Rosales-Corral, S.A.
Title Melatonin and stable circadian rhythms optimize maternal, placental and fetal physiology Type Journal Article
Year 2014 Publication Human Reproduction Update Abbreviated Journal Hum Reprod Update
Volume 20 Issue 2 Pages 293-307
Keywords Human Health; Animals; Antioxidants/physiology; Biological Clocks/physiology; Circadian Rhythm/*physiology; Female; Fetus/*physiology; Humans; Mammals; Melatonin/biosynthesis/*physiology; Mice; Oxidative Stress/physiology; Parturition/physiology; Placenta/metabolism/*physiology; Pre-Eclampsia/etiology/metabolism; Pregnancy; Uterus/metabolism; circadian rhythms; fetus; melatonin; placenta; pre-eclampsia
Abstract BACKGROUND: Research within the last decade has shown melatonin to have previously-unsuspected beneficial actions on the peripheral reproductive organs. Likewise, numerous investigations have documented that stable circadian rhythms are also helpful in maintaining reproductive health. The relationship of melatonin and circadian rhythmicity to maternal and fetal health is summarized in this review. METHODS: Databases were searched for the related published English literature up to 15 May 2013. The search terms used in various combinations included melatonin, circadian rhythms, biological clock, suprachiasmatic nucleus, ovary, pregnancy, uterus, placenta, fetus, pre-eclampsia, intrauterine growth restriction, ischemia-reperfusion, chronodisruption, antioxidants, oxidative stress and free radicals. The results of the studies uncovered are summarized herein. RESULTS: Both melatonin and circadian rhythms impact reproduction, especially during pregnancy. Melatonin is a multifaceted molecule with direct free radical scavenging and indirect antioxidant activities. Melatonin is produced in both the ovary and in the placenta where it protects against molecular mutilation and cellular dysfunction arising from oxidative/nitrosative stress. The placenta, in particular, is often a site of excessive free radical generation due to less than optimal adhesion to the uterine wall, which leads to either persistent hypoxia or intermittent hypoxia and reoxygenation, processes that cause massive free radical generation and organ dysfunction. This may contribute to pre-eclampsia and other disorders which often complicate pregnancy. Melatonin has ameliorated free radical damage to the placenta and to the fetus in experiments using non-human mammals. Likewise, the maintenance of a regular maternal light/dark and sleep/wake cycle is important to stabilize circadian rhythms generated by the maternal central circadian pacemaker, the suprachiasmatic nuclei. Optimal circadian rhythmicity in the mother is important since her circadian clock, either directly or indirectly via the melatonin rhythm, programs the developing master oscillator of the fetus. Experimental studies have shown that disturbed maternal circadian rhythms, referred to as chronodisruption, and perturbed melatonin cycles have negative consequences for the maturing fetal oscillators, which may lead to psychological and behavioral problems in the newborn. To optimize regular circadian rhythms and prevent disturbances of the melatonin cycle during pregnancy, shift work and bright light exposure at night should be avoided, especially during the last trimester of pregnancy. Finally, melatonin synergizes with oxytocin to promote delivery of the fetus. Since blood melatonin levels are normally highest during the dark period, the propensity of childbirth to occur at night may relate to the high levels of melatonin at this time which work in concert with oxytocin to enhance the strength of uterine contractions. CONCLUSIONS: A number of conclusions naturally evolve from the data summarized in this review: (i) melatonin, of both pineal and placental origin, has essential functions in fetal maturation and placenta/uterine homeostasis; (ii) circadian clock genes, which are components of all cells including those in the peripheral reproductive organs, have important roles in reproductive and organismal (fetal and maternal) physiology; (iii) due to the potent antioxidant actions of melatonin, coupled with its virtual absence of toxicity, this indoleamine may have utility in the treatment of pre-eclampsia, intrauterine growth restriction, placental and fetal ischemia/reperfusion, etc. (iv) the propensity for parturition to occur at night may relate to the synergism between the nocturnal increase in melatonin and oxytocin.
Address Department of Cellular and Structural Biology, University of Texas Health Science Center, San Antonio, TX, 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 1355-4786 ISBN Medium
Area Expedition Conference
Notes PMID:24132226 Approved no
Call Number LoNNe @ christopher.kyba @ Serial 504
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Author Stevens, R.G.
Title Light-at-night, circadian disruption and breast cancer: assessment of existing evidence Type Journal Article
Year 2009 Publication International Journal of Epidemiology Abbreviated Journal Int J Epidemiol
Volume 38 Issue 4 Pages 963-970
Keywords Human Health; Animals; Blindness/complications/epidemiology; Breast Neoplasms/epidemiology/*etiology/metabolism; Chronobiology Disorders/*complications/epidemiology/metabolism; Circadian Rhythm/physiology; Disease Models, Animal; Female; Humans; Light Signal Transduction/physiology; Lighting/adverse effects; Melatonin/biosynthesis; Sleep/physiology; Time Factors; *Work Schedule Tolerance
Abstract BACKGROUND: Breast cancer incidence is increasing globally for largely unknown reasons. The possibility that a portion of the breast cancer burden might be explained by the introduction and increasing use of electricity to light the night was suggested >20 years ago. METHODS: The theory is based on nocturnal light-induced disruption of circadian rhythms, notably reduction of melatonin synthesis. It has formed the basis for a series of predictions including that non-day shift work would increase risk, blind women would be at lower risk, long sleep duration would lower risk and community nighttime light level would co-distribute with breast cancer incidence on the population level. RESULTS: Accumulation of epidemiological evidence has accelerated in recent years, reflected in an International Agency for Research on Cancer (IARC) classification of shift work as a probable human carcinogen (2A). There is also a strong rodent model in support of the light-at-night (LAN) idea. CONCLUSION: If a consensus eventually emerges that LAN does increase risk, then the mechanisms for the effect are important to elucidate for intervention and mitigation. The basic understanding of phototransduction for the circadian system, and of the molecular genetics of circadian rhythm generation are both advancing rapidly, and will provide for the development of lighting technologies at home and at work that minimize circadian disruption, while maintaining visual efficiency and aesthetics. In the interim, there are strategies now available to reduce the potential for circadian disruption, which include extending the daily dark period, appreciate nocturnal awakening in the dark, using dim red light for nighttime necessities, and unless recommended by a physician, not taking melatonin tablets.
Address Department of Community Medicine, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT 06030-6325, USA. bugs@uchc.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 0300-5771 ISBN Medium
Area Expedition Conference
Notes PMID:19380369; PMCID:PMC2734067 Approved no
Call Number LoNNe @ christopher.kyba @ Serial 527
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Author Takemura, A.; Ueda, S.; Hiyakawa, N.; Nikaido, Y.
Title A direct influence of moonlight intensity on changes in melatonin production by cultured pineal glands of the golden rabbitfish, Siganus guttatus Type Journal Article
Year 2006 Publication Journal of Pineal Research Abbreviated Journal J Pineal Res
Volume 40 Issue 3 Pages 236-241
Keywords Animals; Circadian Rhythm; *Light; Melatonin/biosynthesis/*secretion; *Moon; Organ Culture Techniques; Perciformes/*physiology; Pineal Gland/physiology/*radiation effects
Abstract Rabbitfish are a restricted lunar-synchronized spawner that spawns around a species-specific lunar phase. It is not known how the fish perceive changes in cues from the moon. One possible explanation is that rabbitfish utilize changes in moonlight intensity to establish synchrony. The purpose of the present study was to examine whether or not the pineal gland of the golden rabbitfish can directly perceive changes in moonlight intensity. Isolated pineal glands were statically cultured under natural or artificial light conditions and melatonin secreted into the culture medium was measured using a time-resolved fluoroimmunoassay. Under an artificial light/dark cycle, melatonin secretion significantly increased during the dark phase. Under continuous light conditions, melatonin secretion was suppressed, while culture under continuous dark conditions seemed to duplicate melatonin secretion corresponding to the light/dark cycle in which the fish were acclimated. When cultured pineal glands were kept under natural light conditions on the dates of the full and the new moon, small amounts of melatonin were secreted at night. Moreover, exposure of cultured pineal glands to artificial and natural light conditions resulted in a significant decrease of melatonin secretion within 2 hr. These results suggest that the isolated pineal gland of golden rabbitfish responds to environmental light cycles and that 'brightness' of the night moon has an influence on melatonin secretion from the isolated pineal gland.
Address Sesoko Station, Tropical Biosphere Research Center, University of the Ryukyus, Motobu, Okinawa, Japan. tilapia@lab.u-ryukyu.ac.jp
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 0742-3098 ISBN Medium
Area Expedition Conference
Notes PMID:16499560 Approved no
Call Number IDA @ john @ Serial 70
Permanent link to this record